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Cellular and Molecular Physiology

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Articles 61 - 90 of 97

Full-Text Articles in Systems and Integrative Physiology

Ablation Of Matrix Metalloproteinase-9 Prevents Cardiomyocytes Contractile Dysfunction In Diabetics., Priyanka Prathipati, Naira Metreveli, Shyam Sundar Nandi, Suresh C. Tyagi, Paras K. Mishra Mar 2016

Ablation Of Matrix Metalloproteinase-9 Prevents Cardiomyocytes Contractile Dysfunction In Diabetics., Priyanka Prathipati, Naira Metreveli, Shyam Sundar Nandi, Suresh C. Tyagi, Paras K. Mishra

Journal Articles: Cellular & Integrative Physiology

Elevated expression and activity of matrix metalloproteinase-9 (MMP9) and decreased contractility of cardiomyocytes are documented in diabetic hearts. However, it is unclear whether MMP is involved in the regulation of contractility of cardiomyocytes in diabetic hearts. In the present study, we tested the hypothesis that MMP9 regulates contractility of cardiomyocytes in diabetic hearts, and ablation of MMP9 prevents impaired contractility of cardiomyocytes in diabetic hearts. To determine the specific role of MMP9 in cardiomyocyte contractility, we used 12-14 week male WT (normoglycemic sibling of Akita), Akita, and Ins(2+∕-)/MMP9(-∕-) (DKO) mice. DKO mice were generated by cross-breeding male Ins2(+∕-) Akita (T1D) …

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Low-Dose Aronia Melanocarpa Concentrate Attenuates Paraquat-Induced Neurotoxicity., Adam J. Case, D Agraz, Iman M. Ahmad, Matthew C. Zimmerman Jan 2016

Low-Dose Aronia Melanocarpa Concentrate Attenuates Paraquat-Induced Neurotoxicity., Adam J. Case, D Agraz, Iman M. Ahmad, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

Herbicides containing paraquat may contribute to the pathogenesis of neurodegenerative disorders such as Parkinson's disease. Paraquat induces reactive oxygen species-mediated apoptosis in neurons, which is a primary mechanism behind its toxicity. We sought to test the effectiveness of a commercially available polyphenol-rich Aronia melanocarpa (aronia berry) concentrate in the amelioration of paraquat-induced neurotoxicity. Considering the abundance of antioxidants in aronia berries, we hypothesized that aronia berry concentrate attenuates the paraquat-induced increase in reactive oxygen species and protects against paraquat-mediated neuronal cell death. Using a neuronal cell culture model, we observed that low doses of aronia berry concentrate protected against paraquat-mediated …

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Angiotensin Ii-Induced Hypertension Is Attenuated By Overexpressing Copper/Zinc Superoxide Dismutase In The Brain Organum Vasculosum Of The Lamina Terminalis., John P. Collister, Heather Taylor-Smith, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman Jan 2016

Angiotensin Ii-Induced Hypertension Is Attenuated By Overexpressing Copper/Zinc Superoxide Dismutase In The Brain Organum Vasculosum Of The Lamina Terminalis., John P. Collister, Heather Taylor-Smith, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

Angiotensin II (AngII) can access the brain via circumventricular organs (CVOs), including the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), to modulate blood pressure. Previous studies have demonstrated a role for both the SFO and OVLT in the hypertensive response to chronic AngII, yet it is unclear which intracellular signaling pathways are involved in this response. Overexpression of copper/zinc superoxide dismutase (CuZnSOD) in the SFO has been shown to attenuate the chronic hypertensive effects of AngII. Presently, we tested the hypothesis that elevated levels of superoxide (O2 (∙-)) in the OVLT contribute to the hypertensive effects …

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Low-Dose Aronia Melanocarpa Concentrate Attenuates Paraquat-Induced Neurotoxicity, Adam J. Case, Daniel Agraz, Iman M. Ahmad, Matthew C. Zimmerman Jan 2016

Low-Dose Aronia Melanocarpa Concentrate Attenuates Paraquat-Induced Neurotoxicity, Adam J. Case, Daniel Agraz, Iman M. Ahmad, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

No abstract provided.

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Angiotensin Ii-Induced Hypertension Is Attenuated By Overexpressing Copper/Zinc Superoxide Dismutase In The Brain Organum Vasculosum Of The Lamina Terminalis., John P. Collister, Heather Taylor-Smith, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman Jan 2016

Angiotensin Ii-Induced Hypertension Is Attenuated By Overexpressing Copper/Zinc Superoxide Dismutase In The Brain Organum Vasculosum Of The Lamina Terminalis., John P. Collister, Heather Taylor-Smith, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

Angiotensin II (AngII) can access the brain via circumventricular organs (CVOs), including the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), to modulate blood pressure. Previous studies have demonstrated a role for both the SFO and OVLT in the hypertensive response to chronic AngII, yet it is unclear which intracellular signaling pathways are involved in this response. Overexpression of copper/zinc superoxide dismutase (CuZnSOD) in the SFO has been shown to attenuate the chronic hypertensive effects of AngII. Presently, we tested the hypothesis that elevated levels of superoxide (O2 (∙-)) in the OVLT contribute to the hypertensive effects …

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Changes In Brain Water Content In The Rainbow Trout (Oncorhynchus Mykiss) And In The Goldfish (Carassius Auratus) Due To High External Ammonia Exposure, Phillip Q.H. Pham-Ho Jan 2016

Changes In Brain Water Content In The Rainbow Trout (Oncorhynchus Mykiss) And In The Goldfish (Carassius Auratus) Due To High External Ammonia Exposure, Phillip Q.H. Pham-Ho

Theses and Dissertations (Comprehensive)

In fishes, hyperammonemia may occur following feeding or exposure to abnormally high concentrations of environmental ammonia due to sewage effluents, agricultural run-off and in crowded aquaculture pens. Increased internal ammonia can result in hyperactivity, convulsions, coma and death. In mammals, it is also associated with potentially fatal brain edema, in which the accumulation of intracellular water results in swelling, increased intracranical pressure and herniation leading to death. Recently it was shown that rainbow trout (Oncorhynchus mykiss) and goldfish (Carassius auratus) experience brain swelling following exposure to high external ammonia (HEA). However, the mechanism of ammonia-induced brain …

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The Role Of Oxidative Stress In The Mechanisms Of Ammonia-Induced Brain Swelling And Tolerance In The Goldfish (Carassius Auratus), David F. Jones Lisser Mr. Jan 2016

The Role Of Oxidative Stress In The Mechanisms Of Ammonia-Induced Brain Swelling And Tolerance In The Goldfish (Carassius Auratus), David F. Jones Lisser Mr.

Theses and Dissertations (Comprehensive)

Toxic build-ups of ammonia can cause potentially fatal brain swelling in mammals, but such swelling is reversible in the anoxia- and ammonia-tolerant goldfish (Carassius auratus). The mechanisms of ammonia-induced brain swelling and tolerance remain elusive, but several studies have suggested a role for reactive oxygen species (ROS), which may damage proteins and lipids in the plasma membrane of astrocytes in the brain. As a result, osmotic gradients across cell membranes may be altered leading to water uptake by astrocytes and swelling. While a role for ROS has been proposed in mammals, no studies have addressed this question in …

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Interaction Between Angiotensin Ii And Bdnf In Modulating Sympathetic Nerve Activity, Bryan K. Becker Dec 2015

Interaction Between Angiotensin Ii And Bdnf In Modulating Sympathetic Nerve Activity, Bryan K. Becker

Theses & Dissertations

Over activation of the sympathetic nervous system is prevalent in many forms of cardiovascular disease such as chronic heart failure (CHF) and hypertension. Although increased neuronal renin-angiotensin system activity in presympathetic neurons has been well implicated in mediating this sympatho-excitation, many of the neuronal effects of angiotensin II (Ang II) signaling remain poorly understood. One particular mechanism of Ang II-mediated increases in presympathetic neuronal activity is through reductions in voltage-gated K+ currents. Another pathway that has profound effects on neuronal K+ currents and that has been previously implicated in Ang II-signaling is brain-derived neurotrophic factor (BDNF) activity through …

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Bdnf Contributes To Angiotensin Ii-Mediated Reductions In Peak Voltage-Gated K+ Current In Cultured Cath.A Cells., Bryan K. Becker, Han-Jun Wang, Changhai Tian, Irving H. Zucker Nov 2015

Bdnf Contributes To Angiotensin Ii-Mediated Reductions In Peak Voltage-Gated K+ Current In Cultured Cath.A Cells., Bryan K. Becker, Han-Jun Wang, Changhai Tian, Irving H. Zucker

Journal Articles: Cellular & Integrative Physiology

Increased central angiotensin II (Ang II) levels contribute to sympathoexcitation in cardiovascular disease states such as chronic heart failure and hypertension. One mechanism by which Ang II increases neuronal excitability is through a decrease in voltage-gated, rapidly inactivating K(+) current (IA); however, little is known about how Ang II signaling results in reduced IA. Brain-derived neurotrophic factor (BDNF) has also been demonstrated to decrease IA and has signaling components common to Ang II. Therefore, we hypothesized that Ang II-mediated suppression of voltage-gated K(+) currents is due, in part, to BDNF signaling. Differentiated CATH.a, catecholaminergic cell line treated with BDNF for …

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Relevance Of The Carotid Body Chemoreflex In The Progression Of Heart Failure., David C. Andrade, Claudia Lucero, Camilo Toledo, Carlos Madrid, Noah J. Marcus, Harold D. Schultz, Rodrigo Del Rio Oct 2015

Relevance Of The Carotid Body Chemoreflex In The Progression Of Heart Failure., David C. Andrade, Claudia Lucero, Camilo Toledo, Carlos Madrid, Noah J. Marcus, Harold D. Schultz, Rodrigo Del Rio

Journal Articles: Cellular & Integrative Physiology

Chronic heart failure (CHF) is a global health problem affecting millions of people. Autonomic dysfunction and disordered breathing patterns are commonly observed in patients with CHF, and both are strongly related to poor prognosis and high mortality risk. Tonic activation of carotid body (CB) chemoreceptors contributes to sympathoexcitation and disordered breathing patterns in experimental models of CHF. Recent studies show that ablation of the CB chemoreceptors improves autonomic function and breathing control in CHF and improves survival. These exciting findings indicate that alterations in CB function are critical to the progression of CHF. Therefore, better understanding of the physiology of …

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Multi-Stress Proteomics: The Global Protein Response To Multiple Environmental Stressors In The Porcelain Crab Petrolisthes Cinctipes, Michael A. Garland Sep 2015

Multi-Stress Proteomics: The Global Protein Response To Multiple Environmental Stressors In The Porcelain Crab Petrolisthes Cinctipes, Michael A. Garland

Master's Theses

Global climate change is increasing the number of hot days along the California coast as well as increasing the incidence of off-shore upwelling events that lower the pH of intertidal seawater; thus, intertidal organisms are experiencing an increase in more than one stress simultaneously. This study seeks to characterize the global protein response of the eurythermal porcelain crab Petrolisthes cinctipes to changes in thermal, pH, and tidal regime treatments, either combined or individually. The first experiment examined temperature stress alone and sought to determine the effect of chronic temperature acclimation on the acute heat shock response. We compared the proteomic …

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Editorial: Carotid Body: A New Target For Rescuing Neural Control Of Cardiorespiratory Balance In Disease., Rodrigo Del Rio, Rodrigo Iturriaga, Harold D. Schultz Jun 2015

Editorial: Carotid Body: A New Target For Rescuing Neural Control Of Cardiorespiratory Balance In Disease., Rodrigo Del Rio, Rodrigo Iturriaga, Harold D. Schultz

Journal Articles: Cellular & Integrative Physiology

No abstract provided.

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Pathological Effects Of Repeated Concussive Tbi In Mouse Models: Periventricular Damage And Ventriculomegaly, Richard H. Wolferz Jr. May 2015

Pathological Effects Of Repeated Concussive Tbi In Mouse Models: Periventricular Damage And Ventriculomegaly, Richard H. Wolferz Jr.

Honors Scholar Theses

Repeated concussive traumatic brain injury (rcTBI) is the most prominent form of head injury affecting the brain, with an estimated 1.7 million Americans affected each year (Kuhn 2012). Neurologists have been concerned about the danger of repeated head impacts since the 1920’s, but researchers have only begun to understand the long-term effects of rcTBI (McKee 2009). Although symptoms can be as mild as dizziness, current research suggests that multiple concussions can lead to a progressive degenerative brain disease known as chronic traumatic encephalopathy (CTE) (Luo 2008, McKee 2009, Kane 2013). Research on the brain is just beginning to scratch the …

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Exercise Ameliorates High Fat Diet Induced Cardiac Dysfunction By Increasing Interleukin 10., Varun Kesherwani, Vishalakshi Chavali, Bryan T. Hackfort, Suresh C. Tyagi, Paras K. Mishra Apr 2015

Exercise Ameliorates High Fat Diet Induced Cardiac Dysfunction By Increasing Interleukin 10., Varun Kesherwani, Vishalakshi Chavali, Bryan T. Hackfort, Suresh C. Tyagi, Paras K. Mishra

Journal Articles: Cellular & Integrative Physiology

Increasing evidence suggests that a sedentary lifestyle and a high fat diet (HFD) leads to cardiomyopathy. Moderate exercise ameliorates cardiac dysfunction, however underlying molecular mechanisms are poorly understood. Increased inflammation due to induction of pro-inflammatory cytokine such as tumor necrosis factor-alpha (TNF-α) and attenuation of anti-inflammatory cytokine such as interleukin 10 (IL-10) contributes to cardiac dysfunction in obese and diabetics. We hypothesized that exercise training ameliorates HFD- induced cardiac dysfunction by mitigating obesity and inflammation through upregulation of IL-10 and downregulation of TNF-α. To test this hypothesis, 8 week old, female C57BL/6J mice were fed with HFD and exercised (swimming …

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Induction Of Autophagy Markers Is Associated With Attenuation Of Mir-133a In Diabetic Heart Failure Patients Undergoing Mechanical Unloading., Shyam Sundar Nandi, Michael J. Duryee, Hamid R. Shahshahan, Geoffrey M. Thiele, Daniel R. Anderson, Paras K. Mishra Apr 2015

Induction Of Autophagy Markers Is Associated With Attenuation Of Mir-133a In Diabetic Heart Failure Patients Undergoing Mechanical Unloading., Shyam Sundar Nandi, Michael J. Duryee, Hamid R. Shahshahan, Geoffrey M. Thiele, Daniel R. Anderson, Paras K. Mishra

Journal Articles: Cellular & Integrative Physiology

Autophagy is ubiquitous in all forms of heart failure and cardioprotective miR-133a is attenuated in human heart failure. Previous reports from heart failure patients undergoing left ventricular assist device (LVAD) implantation demonstrated that autophagy is upregulated in the LV of the failing human heart. Studies in the murine model show that diabetes downregulates miR-133a. However, the role of miR-133a in the regulation of autophagy in diabetic hearts is unclear. We tested the hypothesis that diabetes exacerbates cardiac autophagy by inhibiting miR-133a in heart failure patients undergoing LVAD implantation. The miRNA assay was performed on the LV of 15 diabetic (D) …

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Over-Expression Of Copper/Zinc Superoxide Dismutase In The Median Preoptic Nucleus Attenuates Chronic Angiotensin Ii-Induced Hypertension In The Rat., John P. Collister, Mitch Bellrichard, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman Dec 2014

Over-Expression Of Copper/Zinc Superoxide Dismutase In The Median Preoptic Nucleus Attenuates Chronic Angiotensin Ii-Induced Hypertension In The Rat., John P. Collister, Mitch Bellrichard, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2·-) scavenging enzyme, in …

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Central Role Of Carotid Body Chemoreceptors In Disordered Breathing And Cardiorenal Dysfunction In Chronic Heart Failure., Noah J. Marcus, Rodrigo Del Rio, Harold D. Schultz Nov 2014

Central Role Of Carotid Body Chemoreceptors In Disordered Breathing And Cardiorenal Dysfunction In Chronic Heart Failure., Noah J. Marcus, Rodrigo Del Rio, Harold D. Schultz

Journal Articles: Cellular & Integrative Physiology

Oscillatory breathing (OB) patterns are observed in pre-term infants, patients with cardio-renal impairment, and in otherwise healthy humans exposed to high altitude. Enhanced carotid body (CB) chemoreflex sensitivity is common to all of these populations and is thought to contribute to these abnormal patterns by destabilizing the respiratory control system. OB patterns in chronic heart failure (CHF) patients are associated with greater levels of tonic and chemoreflex-evoked sympathetic nerve activity (SNA), which is associated with greater morbidity and poor prognosis. Enhanced chemoreflex drive may contribute to tonic elevations in SNA by strengthening the relationship between respiratory and sympathetic neural outflow. …

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Eggshell Calcium Regulates Calcium Transport Protein Expression In An Oviparous Snake, Hannah Frye May 2014

Eggshell Calcium Regulates Calcium Transport Protein Expression In An Oviparous Snake, Hannah Frye

Undergraduate Honors Theses

One hypothesis explaining the numerous independent evolutionary transitions from oviparity to viviparity among squamates (snakes and lizards) proposed that squamate embryonic development is independent of eggshell calcium. Recent research showed at least 25% of the calcium in hatchling oviparous squamates is extracted from the shell. Though not a direct test, these results are inconsistent with the hypothesis. To directly test the hypothesis, we removed eggshell calcium (through peeling) early in development of Pantherophis guttatus (corn snake) eggs. Survivorship to hatching did not differ between peeled and intact eggs. Yet hatchlings from peeled eggs were shorter (273.6 ± 3.4 vs. 261.0 …

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Absence Of Manganese Superoxide Dismutase Delays P53-Induced Tumor Formation., Adam J. Case, Frederick E. Domann Jan 2014

Absence Of Manganese Superoxide Dismutase Delays P53-Induced Tumor Formation., Adam J. Case, Frederick E. Domann

Journal Articles: Cellular & Integrative Physiology

BACKGROUND: Manganese superoxide dismutase (MnSOD) is a mitochondrial antioxidant enzyme that is down-regulated in a majority of cancers. Due to this observation, as well as MnSOD's potent antioxidant enzymatic activity, MnSOD has been suggested as a tumor suppressor for over 30 years. However, testing this postulate has proven difficult due to the early post-natal lethality of the MnSOD constitutive knock-out mouse. We have previously used a conditional tissue-specific MnSOD knock-out mouse to study the effects of MnSOD loss on the development of various cell types, but long-term cancer development studies have not been performed. We hypothesized the complete loss of …

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Over-Expressed Copper/Zinc Superoxide Dismutase Localizes To Mitochondria In Neurons Inhibiting The Angiotensin Ii-Mediated Increase In Mitochondrial Superoxide, Shumin Li, Adam J. Case, Rui-Fang Yang, Harold D. Schultz, Matthew C. Zimmerman Jan 2014

Over-Expressed Copper/Zinc Superoxide Dismutase Localizes To Mitochondria In Neurons Inhibiting The Angiotensin Ii-Mediated Increase In Mitochondrial Superoxide, Shumin Li, Adam J. Case, Rui-Fang Yang, Harold D. Schultz, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

Angiotensin II (AngII) is the main effector peptide of the renin-angiotensin system (RAS), and contributes to the pathogenesis of cardiovascular disease by exerting its effects on an array of different cell types, including central neurons. AngII intra-neuronal signaling is mediated, at least in part, by reactive oxygen species, particularly superoxide (O2 (•-)). Recently, it has been discovered that mitochondria are a major subcellular source of AngII-induced O2 (•-). We have previously reported that over-expression of manganese superoxide dismutase (MnSOD), a mitochondrial matrix-localized O2 (•-) scavenging enzyme, inhibits AngII intra-neuronal signaling. Interestingly, over-expression of copper/zinc superoxide dismutase (CuZnSOD), which is believed …

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Aspirin And Low-Molecular Weight Heparin Combination Therapy Effectively Prevents Recurrent Miscarriage In Hyperhomocysteinemic Women., Pratip Chakraborty, Sayani Banerjee, Piyali Saha, Shyam Sundar Nandi, Sunita Sharma, Sourendra K. Goswami, Baidyanath Chakravarty, Syed N. Kabir Sep 2013

Aspirin And Low-Molecular Weight Heparin Combination Therapy Effectively Prevents Recurrent Miscarriage In Hyperhomocysteinemic Women., Pratip Chakraborty, Sayani Banerjee, Piyali Saha, Shyam Sundar Nandi, Sunita Sharma, Sourendra K. Goswami, Baidyanath Chakravarty, Syed N. Kabir

Journal Articles: Cellular & Integrative Physiology

The management of recurrent pregnancy loss (RPL) still remains a great challenge, and women with polycystic ovarian syndrome (PCOS) are at a greater risk for spontaneous abortion. Treatment with low-molecular-weight heparin (LMWH) has become an accepted treatment option for women with RPL; however, the subgroup of women, who are likely to respond to LMWH, has not been precisely identified. The present study evaluated the efficacy of LMWH with reference to PCOS and associated metabolic phenotypes including hyperhomocysteinemia (HHcy), insulin resistance (IR) and obesity. This prospective observational study was conducted at Institute of Reproductive Medicine, Kolkata, India. A total of 967 …

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Intrinsic Apoptotic Pathway: Effects Of Calcium On Murine Cytochrome C Release In Brain And Liver Mitochondria, Dane M. Edwards Apr 2013

Intrinsic Apoptotic Pathway: Effects Of Calcium On Murine Cytochrome C Release In Brain And Liver Mitochondria, Dane M. Edwards

Senior Honors Theses

A cell may use one of three main apoptotic pathways leading to programmed cell death: the extrinsic pathway, the perforin/granzyme pathway and the intrinsic pathway. The most pertinent to this discussion is the intrinsic pathway, which utilizes the mitochondria as an essential intermediary. Mitochondria’s primary function in relation to this pathway is the subsequent release of pro-apoptotic factors including cytochrome c, which activate a caspase cascade leading to the death of the cell. Cytochrome c is released partly due to an increase in cytosolic calcium levels. Two methods of the release of cytochrome c have been proposed. The first is …

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Improved Tolerance To Salt And Water Stress In Drosophila Melanogaster Cells Conferred By Late Embryogenesis Abundant Protein., Matthew Marunde, Dilini Samarajeewa, John Anderson, Shumin Li, Steven Hand, Michael Menze Apr 2013

Improved Tolerance To Salt And Water Stress In Drosophila Melanogaster Cells Conferred By Late Embryogenesis Abundant Protein., Matthew Marunde, Dilini Samarajeewa, John Anderson, Shumin Li, Steven Hand, Michael Menze

Faculty and Staff Scholarship

Mechanisms that govern anhydrobiosis involve the accumulation of highly hydrophilic macromolecules, such as late embryogenesis abundant (LEA) proteins. Group 1 LEA proteins comprised of 181 (AfLEA1.1) and 197 (AfLEA1.3) amino acids were cloned from embryos of Artemia franciscana and expressed in Drosophila melanogaster cells (Kc167). Confocal microscopy revealed a construct composed of green fluorescence protein (GFP) and AfLEA1.3 accumulates in the mitochondria (AfLEA1.3-GFP), while AfLEA1.1-GFP was found in the cytoplasm. In the presence of mixed substrates, oxygen consumption was statistically identical for permeabilized Kc167 control and Kc167-AfLEA1.3 cells. Acute titrations of permeabilized cells with NaCl up to 500 mM led …

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Maintenance Of Mitochondrial Genomic Integrity In The Absence Of Manganese Superoxide Dismutase In Mouse Liver Hepatocytes., Anthony R. Cyr, Kyle E. Brown, Michael L. Mccormick, Mitchell C. Coleman, Adam J. Case, George S. Watts, Bernard W. Futscher, Douglas R. Spitz, Frederick E. Domann Feb 2013

Maintenance Of Mitochondrial Genomic Integrity In The Absence Of Manganese Superoxide Dismutase In Mouse Liver Hepatocytes., Anthony R. Cyr, Kyle E. Brown, Michael L. Mccormick, Mitchell C. Coleman, Adam J. Case, George S. Watts, Bernard W. Futscher, Douglas R. Spitz, Frederick E. Domann

Journal Articles: Cellular & Integrative Physiology

Manganese superoxide dismutase, encoded by the Sod2 gene, is a ubiquitously expressed mitochondrial antioxidant enzyme that is essential for mammalian life. Mice born with constitutive genetic knockout of Sod2 do not survive the neonatal stage, which renders the longitudinal study of the biochemical and metabolic effects of Sod2 loss difficult. However, multiple studies have demonstrated that tissue-specific knockout of Sod2 in murine liver yields no observable gross pathology or injury to the mouse. We hypothesized that Sod2 loss may have sub-pathologic effects on liver biology, including the acquisition of reactive oxygen species-mediated mitochondrial DNA mutations. To evaluate this, we established …

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Improved Tolerance To Salt And Water Stress In Drosophila Melanogaster Cells Conferred By Late Embryogenesis Abundant Protein, Matthew R. Marunde, Dilini A. Samarajeewa, John Anderson, Shumin Li, Steven C. Hand, Michael A. Menze Jan 2013

Improved Tolerance To Salt And Water Stress In Drosophila Melanogaster Cells Conferred By Late Embryogenesis Abundant Protein, Matthew R. Marunde, Dilini A. Samarajeewa, John Anderson, Shumin Li, Steven C. Hand, Michael A. Menze

Faculty Research & Creative Activity

Mechanisms that govern anhydrobiosis involve the accumulation of highly hydrophilic macromolecules, such as late embryogenesis abundant (LEA) proteins. Group 1 LEA proteins comprised of 181 (AfLEA1.1) and 197 (AfLEA1.3) amino acids were cloned from embryos of Artemia franciscana and expressed in Drosophila melanogaster cells (Kc167). Confocal microscopy revealed a construct composed of green fluorescence protein (GFP) and AfLEA1.3 accumulates in the mitochondria (AfLEA1.3-GFP), while AfLEA1.1-GFP was found in the cytoplasm. In the presence of mixed substrates, oxygen consumption was statistically identical for permeabilized Kc167 control and Kc167-AfLEA1.3 cells. Acute titrations of permeabilized cells with NaCl up to 500 mM led …

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Diapause And Anhydrobiosis In Embryos Of Artemia Franciscana: Metabolic Depression, Lea Proteins And Water Stress, Steven C. Handel, Yuvraj Patil, Shumin Li, Nilay Chakraborty, Apurva Borcar, Michael A. Menze, Leaf C. Boswell, Daniel Moore, Mehmet Toner Jan 2013

Diapause And Anhydrobiosis In Embryos Of Artemia Franciscana: Metabolic Depression, Lea Proteins And Water Stress, Steven C. Handel, Yuvraj Patil, Shumin Li, Nilay Chakraborty, Apurva Borcar, Michael A. Menze, Leaf C. Boswell, Daniel Moore, Mehmet Toner

Faculty Research & Creative Activity

Metabolic depression is typically correlated with extended survival of environmental challenge and energy-limitation in early life stages of various invertebrates and vertebrates. Diapause is an ontogenetically-programmed reduction of development and often metabolism seen in many invertebrates. When embryos of Artemia franciscana enter the state of diapause, the overall metabolic depression is estimated to be greater than 99%. These embryos also contain trehalose and express multiple isoforms of Late Embryogenesis Abundant (LEA) proteins, constituents often present in a number of such anhydrobiotic animals. The mRNA levels for LEA proteins are highest in diapause and post-diapause embryos that possess desiccation tolerance, but …

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Diapause And Anhydrobiosis In Embryos Of Artemia Franciscana : Metabolic Depression, Lea Proteins And Water Stress., Steven Handel, Yuvraj Patil, Shumin Li, Nilay Charkraborty, Arpurva Borcar, Michael Menze, Leaf Boswell, Daniel Moore, Mehmet Toner Jan 2013

Diapause And Anhydrobiosis In Embryos Of Artemia Franciscana : Metabolic Depression, Lea Proteins And Water Stress., Steven Handel, Yuvraj Patil, Shumin Li, Nilay Charkraborty, Arpurva Borcar, Michael Menze, Leaf Boswell, Daniel Moore, Mehmet Toner

Faculty and Staff Scholarship

Metabolic depression is typically correlated with extended survival of environmental challenge and energy-limitation in early life stages of various invertebrates and vertebrates. Diapause is an ontogenetically-programmed reduction of development and often metabolism seen in many invertebrates. When embryos of Artemia franciscana enter the state of diapause, the overall metabolic depression is estimated to be greater than 99%. These embryos also contain trehalose and express multiple isoforms of Late Embryogenesis Abundant (LEA) proteins, constituents often present in a number of such anhydrobiotic animals. The mRNA levels for LEA proteins are highest in diapause and post-diapause embryos that possess desiccation tolerance, but …

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Late Embryogenesis Abundant Proteins Protect Human Hepatoma Cells During Acute Desiccation, Shumin Li, Nilay Chakraborty, Apurva Borcar, Michael A. Menze, Mehmet Toner, Steven C. Hand Nov 2012

Late Embryogenesis Abundant Proteins Protect Human Hepatoma Cells During Acute Desiccation, Shumin Li, Nilay Chakraborty, Apurva Borcar, Michael A. Menze, Mehmet Toner, Steven C. Hand

Faculty Research & Creative Activity

Expression of late embryogenesis abundant (LEA) proteins is highly correlated with desiccation tolerance in anhydrobiotic animals, selected land plants, and bacteria. Genes encoding two LEA proteins, one localized to the cytoplasm/nucleus (AfrLEA2) and one targeted to mitochondria (AfrLEA3m), were stably transfected into human HepG2 cells. A trehalose transporterwas used for intracellular loading of this disaccharide. Cellswere rapidly and uniformly desiccated to low water content (<0.12 g H2O/g dry weight) with a recently developed spin-drying technique. Immediately on rehydration, control cells without LEA proteins or trehalose exhibited 0% membrane integrity, comparedwith 98% in cells loaded with trehalose and expressing AfrLEA2 or AfrLEA3m; surprisingly, AfrLEA3m without trehalose conferred 94% protection. Cell proliferation across 7 d showed an 18-fold increase for cells dried with AfrLEA3m and trehalose, compared with 27-fold for nondried controls. LEA proteins dramatically enhance desiccation tolerance in mammalian cells and offer the opportunity for engineering biostability in the dried state.

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Late Embryogenesis Abundant Proteins Protect Human Hepatoma Cells During Acute Desiccation., Shumin Li, Nilay Chakraborty, Apurva Borcar, Michael Menze, Mehmet Toner, Steven Hand Nov 2012

Late Embryogenesis Abundant Proteins Protect Human Hepatoma Cells During Acute Desiccation., Shumin Li, Nilay Chakraborty, Apurva Borcar, Michael Menze, Mehmet Toner, Steven Hand

Faculty and Staff Scholarship

Expression of late embryogenesis abundant (LEA) proteins is highly correlated with desiccation tolerance in anhydrobiotic animals, selected land plants, and bacteria. Genes encoding two LEA proteins, one localized to the cytoplasm/nucleus (AfrLEA2) and one targeted to mitochondria (AfrLEA3m), were stably transfected into human HepG2 cells. A trehalose transporterwas used for intracellular loading of this disaccharide. Cellswere rapidly and uniformly desiccated to low water content (< 0.12 g H2O/g dry weight) with a recently developed spin-drying technique. Immediately on rehydration, control cells without LEA proteins or trehalose exhibited 0% membrane integrity, comparedwith 98% in cells loaded with trehalose and expressing AfrLEA2 or AfrLEA3m; surprisingly, AfrLEA3m without trehalose conferred 94% protection. Cell proliferation across 7 d showed an 18-fold increase for cells dried with AfrLEA3m and trehalose, compared with 27-fold for nondried controls. LEA proteins dramatically enhance desiccation tolerance in mammalian cells and offer the opportunity for engineering biostability in the dried state.

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Metabolic Preconditioning Of Mammalian Cells: Mimetic Agents For Hypoxia Lack Fidelity In Promoting Phosphorylation Of Pyruvate Dehydrogenase, Apurva Borcar, Michael A. Menze, Mehmet Toner, Steven C. Hand Nov 2012

Metabolic Preconditioning Of Mammalian Cells: Mimetic Agents For Hypoxia Lack Fidelity In Promoting Phosphorylation Of Pyruvate Dehydrogenase, Apurva Borcar, Michael A. Menze, Mehmet Toner, Steven C. Hand

Faculty Research & Creative Activity

Induction of HIF-1α by oxygen limitation promotes increased phosphorylation and catalytic depression of mitochondrial pyruvate dehydrogenase (PDH) and an enhanced glycolytic poise in cells. Cobalt chloride and desferrioxamine are widely used as mimics for hypoxia because they increase the levels of HIF-1α. We evaluated the ability of these agents to elicit selected physiological responses to hypoxia as a means to metabolically precondition mammalian cells, but without the detrimental effects of hypoxia. We show that, while CoCl2 does increase HIF-1α in a dose-dependent manner, it unexpectedly and strikingly decreases PDH phosphorylation at E1α sites 1, 2, and 3 (Ser293, Ser300, and …

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