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Articles 1 - 30 of 114
Full-Text Articles in Medicine and Health Sciences
Oma1-Mediated Mitochondrial Dynamics Balance Organellar Homeostasis Upstream Of Cellular Stress Responses, Robert Gilkerson, Harpreet Kaur, Omar Carrillo, Isaiah Ramos
Oma1-Mediated Mitochondrial Dynamics Balance Organellar Homeostasis Upstream Of Cellular Stress Responses, Robert Gilkerson, Harpreet Kaur, Omar Carrillo, Isaiah Ramos
School of Integrative Biological and Chemical Sciences Faculty Publications and Presentations
In response to cellular metabolic and signaling cues, the mitochondrial network employs distinct sets of membrane-shaping factors to dynamically modulate organellar structures through a balance of fission and fusion. While these organellar dynamics mediate mitochondrial structure/function homeostasis, they also directly impact critical cell-wide signaling pathways such as apoptosis, autophagy, and the integrated stress response (ISR). Mitochondrial fission is driven by the recruitment of the cytosolic dynamin-related protein-1 (DRP1), while fusion is carried out by mitofusins 1 and 2 (in the outer membrane) and optic atrophy-1 (OPA1) in the inner membrane. This dynamic balance is highly sensitive to cellular stress; when …
Ksp1 Is An Autophagic Receptor Protein For The Snx4-Assisted Autophagy Of Ssn2/Med13, Sara E Hanley, Stephen D Willis, Steven J Doyle, Randy Strich, Katrina F Cooper
Ksp1 Is An Autophagic Receptor Protein For The Snx4-Assisted Autophagy Of Ssn2/Med13, Sara E Hanley, Stephen D Willis, Steven J Doyle, Randy Strich, Katrina F Cooper
Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship
Ksp1 is a casein II-like kinase whose activity prevents aberrant macroautophagy/autophagy induction in nutrient-rich conditions in yeast. Here, we describe a kinase-independent role of Ksp1 as a novel autophagic receptor protein for Ssn2/Med13, a known cargo of Snx4-assisted autophagy of transcription factors. In this pathway, a subset of conserved transcriptional regulators, Ssn2/Med13, Rim15, and Msn2, are selectively targeted for vacuolar proteolysis following nitrogen starvation, assisted by the sorting nexin heterodimer Snx4-Atg20. Here we show that phagophores also engulf Ksp1 alongside its cargo for vacuolar proteolysis. Ksp1 directly associates with Atg8 following nitrogen starvation at the interface of an Atg8-family interacting …
Susceptibility Of Toxoplasma Gondii To Autophagy In Human Cells Relies On Multiple Interacting Parasite Loci, Nicholas Rinkenberger, Alex Rosenberg, Joshua B Radke, Jaya Bhushan, Tadakimi Tomita, Louis M Weiss, L David Sibley
Susceptibility Of Toxoplasma Gondii To Autophagy In Human Cells Relies On Multiple Interacting Parasite Loci, Nicholas Rinkenberger, Alex Rosenberg, Joshua B Radke, Jaya Bhushan, Tadakimi Tomita, Louis M Weiss, L David Sibley
2020-Current year OA Pubs
Autophagy is a process used by cells to recycle organelles and macromolecules and to eliminate intracellular pathogens. Previous studies have shown that some stains of
Neuroactive Steroid Effects On Autophagy In A Human Embryonic Kidney 293 (Hek) Cell Model, Sofia V Salvatore, Ma Xenia G Ilagan, Hongjin Shu, Peter M Lambert, Ann Benz, Mingxing Qian, Douglas F Covey, Charles F Zorumski, Steven Mennerick
Neuroactive Steroid Effects On Autophagy In A Human Embryonic Kidney 293 (Hek) Cell Model, Sofia V Salvatore, Ma Xenia G Ilagan, Hongjin Shu, Peter M Lambert, Ann Benz, Mingxing Qian, Douglas F Covey, Charles F Zorumski, Steven Mennerick
2020-Current year OA Pubs
Neuropsychiatric and neurodegenerative disorders are correlated with cellular stress. Macroautophagy (autophagy) may represent an important protective pathway to maintain cellular homeostasis and functionality, as it targets cytoplasmic components to lysosomes for degradation and recycling. Given recent evidence that some novel psychiatric treatments, such as the neuroactive steroid (NAS) allopregnanolone (AlloP, brexanolone), may induce autophagy, we stably transfected human embryonic kidney 293 (HEK) cells with a ratiometric fluorescent probe to assay NAS effects on autophagy. We hypothesized that NAS may modulate autophagy in part by the ability of uncharged NAS to readily permeate membranes. Microscopy revealed a weak effect of AlloP …
Manf Stimulates Autophagy And Restores Mitochondrial Homeostasis To Treat Autosomal Dominant Tubulointerstitial Kidney Disease In Mice, Yeawon Kim, Chuang Li, Chenjian Gu, Yili Fang, Eric Tycksen, Terri A Pietka, Jothilingam Sivapackiam, Sun-Ji Park, Fumihiko Urano, Vijay Sharma, Ying Maggie Chen, Et Al.
Manf Stimulates Autophagy And Restores Mitochondrial Homeostasis To Treat Autosomal Dominant Tubulointerstitial Kidney Disease In Mice, Yeawon Kim, Chuang Li, Chenjian Gu, Yili Fang, Eric Tycksen, Terri A Pietka, Jothilingam Sivapackiam, Sun-Ji Park, Fumihiko Urano, Vijay Sharma, Ying Maggie Chen, Et Al.
2020-Current year OA Pubs
Misfolded protein aggregates may cause toxic proteinopathy, including autosomal dominant tubulointerstitial kidney disease due to uromodulin mutations (ADTKD-UMOD), a leading hereditary kidney disease. There are no targeted therapies. In our generated mouse model recapitulating human ADTKD-UMOD carrying a leading UMOD mutation, we show that autophagy/mitophagy and mitochondrial biogenesis are impaired, leading to cGAS-STING activation and tubular injury. Moreover, we demonstrate that inducible tubular overexpression of mesencephalic astrocyte-derived neurotrophic factor (MANF), a secreted endoplasmic reticulum protein, after the onset of disease stimulates autophagy/mitophagy, clears mutant UMOD, and promotes mitochondrial biogenesis through p-AMPK enhancement, thus protecting kidney function in our ADTKD mouse …
Autophagy Modulation And Its Implications On Glioblastoma Treatment, Johnny Chen, Andrea Salinas Rodriguez, Maximiliano Arath Morales, Xiaoqian Fang
Autophagy Modulation And Its Implications On Glioblastoma Treatment, Johnny Chen, Andrea Salinas Rodriguez, Maximiliano Arath Morales, Xiaoqian Fang
School of Medicine Publications and Presentations
Autophagy is a vital cellular process that functions to degrade and recycle damaged organelles into basic metabolites. This allows a cell to adapt to a diverse range of challenging conditions. Autophagy assists in maintaining homeostasis, and it is tightly regulated by the cell. The disruption of autophagy has been associated with many diseases, such as neurodegenerative disorders and cancer. This review will center its discussion on providing an in-depth analysis of the current molecular understanding of autophagy and its relevance to brain tumors. We will delve into the current literature regarding the role of autophagy in glioma pathogenesis by exploring …
Sustained Alternate-Day Fasting Potentiates Doxorubicin Cardiotoxicity, Mualla Ozcan, Zhen Guo, Carla Valenzuela Ripoll, Ahmed Diab, Antonino Picataggi, David Rawnsley, Aynaz Lotfinaghsh, Carmen Bergom, Jeff Szymanski, Daniel Hwang, Jie Zheng, Robert J Hayashi, Pamela K Woodard, Attila Kovacs, Joel Schilling, Babak Razani, Abhinav Diwan, Ali Javaheri, Et Al.
Sustained Alternate-Day Fasting Potentiates Doxorubicin Cardiotoxicity, Mualla Ozcan, Zhen Guo, Carla Valenzuela Ripoll, Ahmed Diab, Antonino Picataggi, David Rawnsley, Aynaz Lotfinaghsh, Carmen Bergom, Jeff Szymanski, Daniel Hwang, Jie Zheng, Robert J Hayashi, Pamela K Woodard, Attila Kovacs, Joel Schilling, Babak Razani, Abhinav Diwan, Ali Javaheri, Et Al.
2020-Current year OA Pubs
Fasting strategies are under active clinical investigation in patients receiving chemotherapy. Prior murine studies suggest that alternate-day fasting may attenuate doxorubicin cardiotoxicity and stimulate nuclear translocation of transcription factor EB (TFEB), a master regulator of autophagy and lysosomal biogenesis. In this study, human heart tissue from patients with doxorubicin-induced heart failure demonstrated increased nuclear TFEB protein. In mice treated with doxorubicin, alternate-day fasting or viral TFEB transduction increased mortality and impaired cardiac function. Mice randomized to alternate-day fasting plus doxorubicin exhibited increased TFEB nuclear translocation in the myocardium. When combined with doxorubicin, cardiomyocyte-specific TFEB overexpression provoked cardiac remodeling, while systemic …
Autophagy Prevents Early Proinflammatory Responses And Neutrophil Recruitment During Mycobacterium Tuberculosis Infection Without Affecting Pathogen Burden In Macrophages, Rachel L. Kinsella, Jacqueline M. Kimmey, Asya Smirnov, Reilly Woodson, Margaret R. Gaggioli, Sthefany M. Chavez, Darren Kreamalmeyer, Christina L. Stallings
Autophagy Prevents Early Proinflammatory Responses And Neutrophil Recruitment During Mycobacterium Tuberculosis Infection Without Affecting Pathogen Burden In Macrophages, Rachel L. Kinsella, Jacqueline M. Kimmey, Asya Smirnov, Reilly Woodson, Margaret R. Gaggioli, Sthefany M. Chavez, Darren Kreamalmeyer, Christina L. Stallings
2020-Current year OA Pubs
The immune response to Mycobacterium tuberculosis infection determines tuberculosis disease outcomes, yet we have an incomplete understanding of what immune factors contribute to a protective immune response. Neutrophilic inflammation has been associated with poor disease prognosis in humans and in animal models during M. tuberculosis infection and, therefore, must be tightly regulated. ATG5 is an essential autophagy protein that is required in innate immune cells to control neutrophil-dominated inflammation and promote survival during M. tuberculosis infection; however, the mechanistic basis for how ATG5 regulates neutrophil recruitment is unknown. To interrogate what innate immune cells require ATG5 to control neutrophil recruitment …
The Mitophagy Receptor Bnip3 Is Critical For The Regulation Of Metabolic Homeostasis And Mitochondrial Function In The Nucleus Pulposus Cells Of The Intervertebral Disc, Vedavathi Madhu, Miriam Hernandez-Meadows, Paige K Boneski, Yunping Qiu, Anyonya R Guntur, Irwin J Kurland, Ruteja A Barve, Makarand V Risbud
The Mitophagy Receptor Bnip3 Is Critical For The Regulation Of Metabolic Homeostasis And Mitochondrial Function In The Nucleus Pulposus Cells Of The Intervertebral Disc, Vedavathi Madhu, Miriam Hernandez-Meadows, Paige K Boneski, Yunping Qiu, Anyonya R Guntur, Irwin J Kurland, Ruteja A Barve, Makarand V Risbud
2020-Current year OA Pubs
The contribution of mitochondria to the metabolic function of hypoxic NP cells has been overlooked. We have shown that NP cells contain networked mitochondria and that mitochondrial translocation of BNIP3 mediates hypoxia-induced mitophagy. However, whether BNIP3 also plays a role in governing mitochondrial function and metabolism in hypoxic NP cells is not known. BNIP3 knockdown altered mitochondrial morphology, and number, and increased mitophagy. Interestingly, BNIP3 deficiency in NP cells reduced glycolytic capacity reflected by lower production of lactate/H
Circadian Clock Protein Bmal1 Broadly Influences Autophagy And Endolysosomal Function In Astrocytes, Celia A Mckee, Alexander J Polino, Melvin W King, Erik S Musiek
Circadian Clock Protein Bmal1 Broadly Influences Autophagy And Endolysosomal Function In Astrocytes, Celia A Mckee, Alexander J Polino, Melvin W King, Erik S Musiek
2020-Current year OA Pubs
An emerging role for the circadian clock in autophagy and lysosome function has opened new avenues for exploration in the field of neurodegeneration. The daily rhythms of circadian clock proteins may coordinate gene expression programs involved not only in daily rhythms but in many cellular processes. In the brain, astrocytes are critical for sensing and responding to extracellular cues to support neurons. The core clock protein BMAL1 serves as the primary positive circadian transcriptional regulator and its depletion in astrocytes not only disrupts circadian function but also leads to a unique cell-autonomous activation phenotype. We report here that astrocyte-specific deletion …
Myeloid Autophagy Genes Protect Mice Against Fatal Tnf- And Lps-Induced Cytokine Storm Syndromes, Ya-Ting Wang, Amy Sansone, Asya Smirnov, Christina L Stallings, Anthony Orvedahl
Myeloid Autophagy Genes Protect Mice Against Fatal Tnf- And Lps-Induced Cytokine Storm Syndromes, Ya-Ting Wang, Amy Sansone, Asya Smirnov, Christina L Stallings, Anthony Orvedahl
2020-Current year OA Pubs
ATG5: autophagy related 5; ATG7: autophagy related 7; ATG14: autophagy related 14; ATG16L1: autophagy related 16-like 1 (S. cerevisiae); BECN1: beclin 1, autophagy related; CASP1: caspase 1; CASP4/CASP11: caspase 4, apoptosis-related cysteine peptidase; CIM: conditionally immortalized macrophage; CLP: cecal ligation and puncture; CSS: cytokine storm syndrome; DC: dendritic cell; IFNG/IFNγ: interferon gamma; IFNGR1: interferon gamma receptor 1; ip: intraperitoneal; iv: intravenous; IL12/p70: interleukin 12, p70 heterodimer; IL18: Interleukin 18; ITGAX/CD11c: integrin alpha X; LAP: LC3-associated phagocytosis; LPS: lipopolysaccharide; LYZ2/LYSM: lysozyme 2; MAP1LC3A/LC3: microtubule-associated protein 1 light chain 3 alpha; RB1CC1/FIP200: RB1-inducible coiled-coil 1; S100A8/MRP8: S100 calcium binding protein A8 (calgranulin …
Utility Of Autophagy In Treating Alzheimer’S Disease, Matthew H. Bautista, Jiani Hu
Utility Of Autophagy In Treating Alzheimer’S Disease, Matthew H. Bautista, Jiani Hu
Medical Student Research Symposium
Alzheimer’s Disease (AD) is the most common cause of dementia in developed countries. The global prevalence is estimated to be as high as 24 million and is expected to continue growing. Despite more than 100 thousand papers on AD encompassing several decades of research, our understanding of the underlying pathogenesis remains limited, consequently contributing to the stagnancy in developing effective therapeutic treatment options. Enormous data in the literature provides opportunities to theoretically evaluate the most likely effective approach for this disease. By digging into the relationship between autophagy and risk factors of AD, we find that autophagy is directly or …
Tnk2/Ack1-Mediated Phosphorylation Of Atp5f1a (Atp Synthase F1 Subunit Alpha) Selectively Augments Survival Of Prostate Cancer While Engendering Mitochondrial Vulnerability, Surbhi Chouhan, Mithila Sawant, Cody Weimholt, Jingqin Luo, Robert W Sprung, Mailyn Terrado, David M Mueller, H Shelton Earp, Nupam P. Mahajan
Tnk2/Ack1-Mediated Phosphorylation Of Atp5f1a (Atp Synthase F1 Subunit Alpha) Selectively Augments Survival Of Prostate Cancer While Engendering Mitochondrial Vulnerability, Surbhi Chouhan, Mithila Sawant, Cody Weimholt, Jingqin Luo, Robert W Sprung, Mailyn Terrado, David M Mueller, H Shelton Earp, Nupam P. Mahajan
2020-Current year OA Pubs
The challenge of rapid macromolecular synthesis enforces the energy-hungry cancer cell mitochondria to switch their metabolic phenotypes, accomplished by activation of oncogenic tyrosine kinases. Precisely how kinase activity is directly exploited by cancer cell mitochondria to meet high-energy demand, remains to be deciphered. Here we show that a non-receptor tyrosine kinase, TNK2/ACK1 (tyrosine kinase non receptor 2), phosphorylated ATP5F1A (ATP synthase F1 subunit alpha) at Tyr243 and Tyr246 (Tyr200 and 203 in the mature protein, respectively) that not only increased the stability of complex V, but also increased mitochondrial energy output in cancer cells. Further, phospho-ATP5F1A (p-Y-ATP5F1A) prevented its binding …
Autophagy Requirements For Eye Lens Differentiation And Transparency, Lisa Brennan, M Joseph Costello, J Fielding Hejtmancik, A. Menko, S Amer Riazuddin, Alan Shiels, Marc Kantorow
Autophagy Requirements For Eye Lens Differentiation And Transparency, Lisa Brennan, M Joseph Costello, J Fielding Hejtmancik, A. Menko, S Amer Riazuddin, Alan Shiels, Marc Kantorow
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Recent evidence points to autophagy as an essential cellular requirement for achieving the mature structure, homeostasis, and transparency of the lens. Collective evidence from multiple laboratories using chick, mouse, primate, and human model systems provides evidence that classic autophagy structures, ranging from double-membrane autophagosomes to single-membrane autolysosomes, are found throughout the lens in both undifferentiated lens epithelial cells and maturing lens fiber cells. Recently, key autophagy signaling pathways have been identified to initiate critical steps in the lens differentiation program, including the elimination of organelles to form the core lens organelle-free zone. Other recent studies using ex vivo lens culture …
Autophagy Requirements For Eye Lens Differentiation And Transparency, Lisa Brennan, M Joseph Costello, J Fielding Hejtmancik, A Sue Menko, S Amer Riazuddin, Alan Shiels, Marc Kantorow
Autophagy Requirements For Eye Lens Differentiation And Transparency, Lisa Brennan, M Joseph Costello, J Fielding Hejtmancik, A Sue Menko, S Amer Riazuddin, Alan Shiels, Marc Kantorow
2020-Current year OA Pubs
Recent evidence points to autophagy as an essential cellular requirement for achieving the mature structure, homeostasis, and transparency of the lens. Collective evidence from multiple laboratories using chick, mouse, primate, and human model systems provides evidence that classic autophagy structures, ranging from double-membrane autophagosomes to single-membrane autolysosomes, are found throughout the lens in both undifferentiated lens epithelial cells and maturing lens fiber cells. Recently, key autophagy signaling pathways have been identified to initiate critical steps in the lens differentiation program, including the elimination of organelles to form the core lens organelle-free zone. Other recent studies using ex vivo lens culture …
On The Potential Therapeutic Roles Of Taurine In Autism Spectrum Disorder, Alberto Rubio-Casillas, Elrashdy M. Redwan, Vladimir N. Uversky
On The Potential Therapeutic Roles Of Taurine In Autism Spectrum Disorder, Alberto Rubio-Casillas, Elrashdy M. Redwan, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Contemporary research has found that people with autism spectrum disorder (ASD) exhibit aberrant immunological function, with a shift toward increased cytokine production and unusual cell function. Microglia and astroglia were found to be significantly activated in immuno-cytochemical studies, and cytokine analysis revealed that the macrophage chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and transforming growth factor β-1 (TGFB-1), all generated in the neuroglia, constituted the most predominant cytokines in the brain. Taurine (2-aminoethanesulfonic acid) is a promising therapeutic molecule able to increase the activity of antioxidant enzymes and ATPase, which may be protective against aluminum-induced neurotoxicity. …
Autophagy And Apoptosis: Current Challenges Of Treatment And Drug Resistance In Multiple Myeloma., Omar S Al-Odat, Daniel A Guirguis, Nicole K Schmalbach, Gabriella Yao, Tulin Budak-Alpdogan, Subash C. Jonnalagadda, Manoj K Pandey
Autophagy And Apoptosis: Current Challenges Of Treatment And Drug Resistance In Multiple Myeloma., Omar S Al-Odat, Daniel A Guirguis, Nicole K Schmalbach, Gabriella Yao, Tulin Budak-Alpdogan, Subash C. Jonnalagadda, Manoj K Pandey
Cooper Medical School of Rowan University Faculty Scholarship
Over the past two decades, the natural history of multiple myeloma (MM) has evolved dramatically, owing primarily to novel agents targeting MM in the bone marrow microenvironment (BMM) pathways. However, the mechanisms of resistance acquisition remain a mystery and are poorly understood. Autophagy and apoptosis are tightly controlled processes and play a critical role in the cell growth, development, and survival of MM. Genetic instability and abnormalities are two hallmarks of MM. During MM progression, plasma malignant cells become genetically unstable and activate various signaling pathways, resulting in the overexpression of abnormal proteins that disrupt autophagy and apoptosis biological processes. …
Mitochondrial Autophagy In Ischemic Aged Livers, Jae-Sung Kim, William C Chapman, Yiing Lin
Mitochondrial Autophagy In Ischemic Aged Livers, Jae-Sung Kim, William C Chapman, Yiing Lin
2020-Current year OA Pubs
Mitochondrial autophagy (mitophagy) is a central catabolic event for mitochondrial quality control. Defective or insufficient mitophagy, thus, can result in mitochondrial dysfunction, and ultimately cell death. There is a strong causal relationship between ischemia/reperfusion (I/R) injury and mitochondrial dysfunction following liver resection and transplantation. Compared to young patients, elderly patients poorly tolerate I/R injury. Accumulation of abnormal mitochondria after I/R is more prominent in aged livers than in young counterparts. This review highlights how altered autophagy is mechanistically involved in age-dependent hypersensitivity to reperfusion injury.
Principles Of Dormancy Evident In High-Grade Serous Ovarian Cancer, Trevor G. Shepherd, Frederick A. Dick
Principles Of Dormancy Evident In High-Grade Serous Ovarian Cancer, Trevor G. Shepherd, Frederick A. Dick
Paediatrics Publications
In cancer, dormancy refers to a clinical state in which microscopic residual disease becomes non-proliferative and is largely refractory to chemotherapy. Dormancy was first described in breast cancer where disease can remain undetected for decades, ultimately leading to relapse and clinical presentation of the original malignancy. A long latency period can be explained by withdrawal from cell proliferation (cellular dormancy), or a balance between proliferation and cell death that retains low levels of residual disease (tumor mass dormancy). Research into cellular dormancy has revealed features that define this state. They include arrest of cell proliferation, altered cellular metabolism, and unique …
Caspase-8 Inactivation Drives Autophagy-Dependent Inflammasome Activation In Myeloid Cells., Yung-Hsuan Wu, Shu-Ting Mo, I-Ting Chen, Fu-Yi Hsieh, Shie-Liang Hsieh, Jianke Zhang, Ming-Zong Lai
Caspase-8 Inactivation Drives Autophagy-Dependent Inflammasome Activation In Myeloid Cells., Yung-Hsuan Wu, Shu-Ting Mo, I-Ting Chen, Fu-Yi Hsieh, Shie-Liang Hsieh, Jianke Zhang, Ming-Zong Lai
Department of Microbiology and Immunology Faculty Papers
Caspase-8 activity controls the switch from cell death to pyroptosis when apoptosis and necroptosis are blocked, yet how caspase-8 inactivation induces inflammasome assembly remains unclear. We show that caspase-8 inhibition via IETD treatment in Toll-like receptor (TLR)-primed Fadd-/-Ripk3-/- myeloid cells promoted interleukin-1β (IL-1β) and IL-18 production through inflammasome activation. Caspase-8, caspase-1/11, and functional GSDMD, but not NLRP3 or RIPK1 activity, proved essential for IETD-triggered inflammasome activation. Autophagy became prominent in IETD-treated Fadd-/-Ripk3-/- macrophages, and inhibiting it attenuated IETD-induced cell death and IL-1β/IL-18 production. In contrast, inhibiting GSDMD or autophagy did not prevent IETD-induced septic …
Promotion Of A Synthetic Degradation Of Activated Stat6 By Parp-1 Inhibition: Roles Of Poly(Adp-Ribosyl)Ation, Calpains And Autophagy, Jeffrey Wang, Mohamed A. Ghonim, Salome V. Ibba, Hanh H. Luu, Yucel Aydin, Peter A. Greer, A. Hamid Boulares
Promotion Of A Synthetic Degradation Of Activated Stat6 By Parp-1 Inhibition: Roles Of Poly(Adp-Ribosyl)Ation, Calpains And Autophagy, Jeffrey Wang, Mohamed A. Ghonim, Salome V. Ibba, Hanh H. Luu, Yucel Aydin, Peter A. Greer, A. Hamid Boulares
School of Medicine Faculty Publications
Background: We reported that PARP-1 regulates genes whose products are crucial for asthma, in part, by controlling STAT6 integrity speculatively through a calpain-dependent mechanism. We wished to decipher the PARP-1/STAT6 relationship in the context of intracellular trafficking and promoter occupancy of the transcription factor on target genes, its integrity in the presence of calpains, and its connection to autophagy. Methods: This study was conducted using primary splenocytes or fibroblasts derived from wild-type or PARP-1−/− mice and Jurkat T cells to mimic Th2 inflammation. Results: We show that the role for PARP-1 in expression of IL-4-induced genes (e.g. gata-3) in splenocytes …
A Protocol To Induce Systemic Autophagy And Increase Energy Metabolism In Mice Using Pegylated Arginine Deiminase, Yiming Zhang, Brian J. Debosch
A Protocol To Induce Systemic Autophagy And Increase Energy Metabolism In Mice Using Pegylated Arginine Deiminase, Yiming Zhang, Brian J. Debosch
2020-Current year OA Pubs
Obesity is a prevalent metabolic disorder worldwide. Here, we describe a comprehensive protocol using pegylated arginine deiminase (ADI-EPG 20) to apply the concept that arginine depletion induces systemic autophagy to drive whole-body energy metabolism and weight loss in mice. We detail the steps for cohort setup, mouse husbandry, and treatment and provide expected results under these conditions. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2022a, 2022b).
Antiaging Mechanism Of Natural Compounds: Effects On Autophagy And Oxidative Stress., Elizabeth Taylor, Yujin Kim, Kaleb Zhang, Lenne Chau, Bao Chieu Nguyen, Srujana Rayalam, Xinyu Wang
Antiaging Mechanism Of Natural Compounds: Effects On Autophagy And Oxidative Stress., Elizabeth Taylor, Yujin Kim, Kaleb Zhang, Lenne Chau, Bao Chieu Nguyen, Srujana Rayalam, Xinyu Wang
PCOM Scholarly Papers
Aging is a natural biological process that manifests as the progressive loss of function in cells, tissues, and organs. Because mechanisms that are meant to promote cellular longevity tend to decrease in effectiveness with age, it is no surprise that aging presents as a major risk factor for many diseases such as cardiovascular disease, neurodegenerative disorders, cancer, and diabetes. Oxidative stress, an imbalance between the intracellular antioxidant and overproduction of reactive oxygen species, is known to promote the aging process. Autophagy, a major pathway for protein turnover, is considered as one of the hallmarks of aging. Given the progressive physiologic …
Activation Of Autophagic Flux Maintains Mitochondrial Homeostasis During Cardiac Ischemia/Reperfusion Injury, Lihao He, Sumanth D Prabhu, Et Al
Activation Of Autophagic Flux Maintains Mitochondrial Homeostasis During Cardiac Ischemia/Reperfusion Injury, Lihao He, Sumanth D Prabhu, Et Al
2020-Current year OA Pubs
Reperfusion injury after extended ischemia accounts for approximately 50% of myocardial infarct size, and there is no standard therapy. HDAC inhibition reduces infarct size and enhances cardiomyocyte autophagy and PGC1α-mediated mitochondrial biogenesis when administered at the time of reperfusion. Furthermore, a specific autophagy-inducing peptide, Tat-Beclin 1 (TB), reduces infarct size when administered at the time of reperfusion. However, since SAHA affects multiple pathways in addition to inducing autophagy, whether autophagic flux induced by TB maintains mitochondrial homeostasis during ischemia/reperfusion (I/R) injury is unknown. We tested whether the augmentation of autophagic flux by TB has cardioprotection by preserving mitochondrial homeostasis both …
Effect Of Injury Mechanism And Severity On The Molecular Pathophysiology Of Traumatic Brain Injury, Brandon Mcdonald
Effect Of Injury Mechanism And Severity On The Molecular Pathophysiology Of Traumatic Brain Injury, Brandon Mcdonald
Department of Biological Systems Engineering: Dissertations and Theses
Traumatic brain injury (TBI) mechanism and severity are heterogenous clinically, resulting in a multitude of physical, cognitive, and behavioral deficits. However, approximately 80% suffer from milder injuries. Thus, examining pathophysiological changes associated with mild TBI is imperative for improving clinical translation and evaluating the efficacy of potential therapeutic strategies. Through this work, we developed models of TBI, ranging in both injury mechanism and severity, using an electromagnetic controlled cortical impact (CCI) device. First, we characterized and optimized a closed head, mild TBI model (DTBI) to determine the clinical translatability and practicality of producing repeated mild injuries. Interestingly, we determined that …
Endothelial Autophagy In Coronary Microvascular Dysfunction And Cardiovascular Disease, Fujie Zhao, Ganesh Satyanarayana, Zheng Zhang, Jianli Zhao, Xin-Liang Ma, Yajing Wang
Endothelial Autophagy In Coronary Microvascular Dysfunction And Cardiovascular Disease, Fujie Zhao, Ganesh Satyanarayana, Zheng Zhang, Jianli Zhao, Xin-Liang Ma, Yajing Wang
Department of Emergency Medicine Faculty Papers
Coronary microvascular dysfunction (CMD) refers to a subset of structural and/or functional disorders of coronary microcirculation that lead to impaired coronary blood flow and eventually myocardial ischemia. Amid the growing knowledge of the pathophysiological mechanisms and the development of advanced tools for assessment, CMD has emerged as a prevalent cause of a broad spectrum of cardiovascular diseases (CVDs), including obstructive and nonobstructive coronary artery disease, diabetic cardiomyopathy, and heart failure with preserved ejection fraction. Of note, the endothelium exerts vital functions in regulating coronary microvascular and cardiac function. Importantly, insufficient or uncontrolled activation of endothelial autophagy facilitates the pathogenesis of …
Human Macrophages Exhibit Gm-Csf Dependent Restriction Of Mycobacterium Tuberculosis Infection Via Regulating Their Self-Survival, Differentiation And Metabolism, Abhishek Mishra, Vipul K. Singh, Chinnaswamy Jagannath, Margaret Sunitha Selvaraj, Selvakumar Subbian, Blanca I. Restrepo, Marie-Claire Gauduin, Arshad Khan
Human Macrophages Exhibit Gm-Csf Dependent Restriction Of Mycobacterium Tuberculosis Infection Via Regulating Their Self-Survival, Differentiation And Metabolism, Abhishek Mishra, Vipul K. Singh, Chinnaswamy Jagannath, Margaret Sunitha Selvaraj, Selvakumar Subbian, Blanca I. Restrepo, Marie-Claire Gauduin, Arshad Khan
School of Medicine Publications and Presentations
GM-CSF is an important cytokine that regulates the proliferation of monocytes/macrophages and its various functions during health and disease. Although growing evidences support the notion that GM-CSF could play a major role in immunity against tuberculosis (TB) infection, the mechanism of GM-CSF mediated protective effect against TB remains largely unknown. Here in this study we examined the secreted levels of GM-CSF by human macrophages from different donors along with the GM-CSF dependent cellular processes that are critical for control of M. tuberculosis infection. While macrophage of different donors varied in their ability to produce GM-CSF, a significant correlation was observed …
Genome-Wide Transcript And Protein Analysis Highlights The Role Of Protein Homeostasis In The Aging Mouse Heart., Isabela Gerdes Gyuricza, Joel M Chick, Gregory R Keele, Andrew Deighan, Steven C. Munger, Ron Korstanje, Steven P Gygi, Gary Churchill
Genome-Wide Transcript And Protein Analysis Highlights The Role Of Protein Homeostasis In The Aging Mouse Heart., Isabela Gerdes Gyuricza, Joel M Chick, Gregory R Keele, Andrew Deighan, Steven C. Munger, Ron Korstanje, Steven P Gygi, Gary Churchill
Faculty Research 2022
Investigation of the molecular mechanisms of aging in the human heart is challenging because of confounding factors, such as diet and medications, as well as limited access to tissues from healthy aging individuals. The laboratory mouse provides an ideal model to study aging in healthy individuals in a controlled environment. However, previous mouse studies have examined only a narrow range of the genetic variation that shapes individual differences during aging. Here, we analyze transcriptome and proteome data from 185 genetically diverse male and female mice at ages 6, 12, and 18 mo to characterize molecular changes that occur in the …
The Role Of Mtorc1 In Autophagy As It Relates To Cancer, Olivia Robinson
The Role Of Mtorc1 In Autophagy As It Relates To Cancer, Olivia Robinson
Senior Honors Theses
The mammalian target of rapamycin complex 1, mTORC1, is composed of several subunit proteins with many cellular responsibilities including participation in a complex cell signaling cascade leading to autophagy, which is the regulated degradation of cell components. mTORC1 is frequently mutated or dysregulated within human cancer. Normally, mTORC1 functions to provide efficient regulation of autophagy according to intracellular levels of growth factors, amino acids, nutrients, oxygen levels, and more that can either inhibit mTORC1 and upregulate autophagy or activate mTORC1 and downregulate autophagy. A better understanding of mTORC1 is imperative to preparing cancer therapy treatments. Various cancerous tissue types require …
Arsenic Toxicity On Metabolism And Autophagy In Adipose And Muscle Tissues, Seung-Hyun Ro, Jiyoung Bae, Yura Jang, Jacob Myers, Soonkyu Chung, Jiujiu Yu, Sathish Kumar Natarajan, Rodrigo Franco, Hyun-Seob Song
Arsenic Toxicity On Metabolism And Autophagy In Adipose And Muscle Tissues, Seung-Hyun Ro, Jiyoung Bae, Yura Jang, Jacob Myers, Soonkyu Chung, Jiujiu Yu, Sathish Kumar Natarajan, Rodrigo Franco, Hyun-Seob Song
Department of Microbiology and Immunology Faculty Papers
Arsenic, a naturally occurring metalloid derived from the environment, has been studied worldwide for its causative effects in various cancers. However, the effects of arsenic toxicity on the development and progression of metabolic syndrome, including obesity and diabetes, has received less attention. Many studies suggest that metabolic dysfunction and autophagy dysregulation of adipose and muscle tissues are closely related to the development of metabolic disease. In the USA, arsenic contamination has been reported in some ground water, soil and grain samples in major agricultural regions, but the effects on adipose and muscle tissue metabolism and autophagy have not been investigated …