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Articles 1 - 12 of 12
Full-Text Articles in Medicine and Health Sciences
Possible Molecular Mechanisms Underlying Age-Related Cardiomyocyte Apoptosis In The F344xbn Rat Heart, Sunil Kakarla, Kevin Rice, Anjaiah Katta, Satyanarayana Paturi, Miaozong Wu, Madhukar Kolli, Saba Keshavarzian, Kamran Manzoor, Paulette Wehner, Eric Blough
Possible Molecular Mechanisms Underlying Age-Related Cardiomyocyte Apoptosis In The F344xbn Rat Heart, Sunil Kakarla, Kevin Rice, Anjaiah Katta, Satyanarayana Paturi, Miaozong Wu, Madhukar Kolli, Saba Keshavarzian, Kamran Manzoor, Paulette Wehner, Eric Blough
Paulette S. Wehner
Despite advances in treatment, age-related cardiac dysfunction still remains a leading cause of cardiovascular death. Recent data have suggested that increases in cardiomyocyte apoptosis may be involved in the pathological remodeling of heart. Here, we examine the effects of aging on cardiomyocyte apoptosis in 6-, 30-, and 36-month-old Fischer344xBrown Norway F1 hybrid rats (F344XBN). Compared with 6-month hearts, aged hearts exhibited increased TdT-mediated dUTP nick end labeling–positive nuclei, caspase-3 activation, caspase-dependent cleavage of α-fodrin and diminished phosphorylation of protein kinase B/Akt (Thr 308). These age-dependent increases in cardiomyocyte apoptosis were associated with alterations in the composition of the cardiac dystrophin …
Possible Molecular Mechanisms Underlying Age-Related Cardiomyocyte Apoptosis In The F344xbn Rat Heart, Sunil Kakarla, Kevin Rice, Anjaiah Katta, Satyanarayana Paturi, Miaozong Wu, Madhukar Kolli, Saba Keshavarzian, Kamran Manzoor, Paulette Wehner, Eric Blough
Possible Molecular Mechanisms Underlying Age-Related Cardiomyocyte Apoptosis In The F344xbn Rat Heart, Sunil Kakarla, Kevin Rice, Anjaiah Katta, Satyanarayana Paturi, Miaozong Wu, Madhukar Kolli, Saba Keshavarzian, Kamran Manzoor, Paulette Wehner, Eric Blough
Kevin M Rice
Despite advances in treatment, age-related cardiac dysfunction still remains a leading cause of cardiovascular death. Recent data have suggested that increases in cardiomyocyte apoptosis may be involved in the pathological remodeling of heart. Here, we examine the effects of aging on cardiomyocyte apoptosis in 6-, 30-, and 36-month-old Fischer344xBrown Norway F1 hybrid rats (F344XBN). Compared with 6-month hearts, aged hearts exhibited increased TdT-mediated dUTP nick end labeling–positive nuclei, caspase-3 activation, caspase-dependent cleavage of α-fodrin and diminished phosphorylation of protein kinase B/Akt (Thr 308). These age-dependent increases in cardiomyocyte apoptosis were associated with alterations in the composition of the cardiac dystrophin …
Initial Evidence Of Endothelial Cell Apoptosis As A Mechanism Of Systemic Capillary Leak Syndrome, Ragheb Assaly, Dan Olson, Jeffrey Hammersley, Pan-Sheng Fan, Jiang Liu, Joseph Shapiro, M. Kahaleh
Initial Evidence Of Endothelial Cell Apoptosis As A Mechanism Of Systemic Capillary Leak Syndrome, Ragheb Assaly, Dan Olson, Jeffrey Hammersley, Pan-Sheng Fan, Jiang Liu, Joseph Shapiro, M. Kahaleh
Jiang Liu
Background: Systemic capillary leak syndrome (SCLS) is a rare disorder of unknown etiology that is characterized by acute recurrent attacks of hypovolemic shock commonly following an inflammatory stimulus such as a viral illness. Prophylactic therapy is generally ineffective, and the outcome is frequently fatal. Methods: In order to investigate the cellular mechanisms leading to SCLS, we examined the effects of sera from two patients with active SCLS on microvascular endothelial cell apoptosis in vitro. Apoptosis was determined by morphologic criteria, DNA fragmentation, annexin V stain, and by a quantitative photometric assay. The apoptotic pathway was investigated by Western blot of …
Possible Molecular Mechanisms Underlying Age-Related Cardiomyocyte Apoptosis In The F344xbn Rat Heart, Sunil Kakarla, Kevin Rice, Anjaiah Katta, Satyanarayana Paturi, Miaozong Wu, Madhukar Kolli, Saba Keshavarzian, Kamran Manzoor, Paulette Wehner, Eric Blough
Possible Molecular Mechanisms Underlying Age-Related Cardiomyocyte Apoptosis In The F344xbn Rat Heart, Sunil Kakarla, Kevin Rice, Anjaiah Katta, Satyanarayana Paturi, Miaozong Wu, Madhukar Kolli, Saba Keshavarzian, Kamran Manzoor, Paulette Wehner, Eric Blough
Eric Blough
Despite advances in treatment, age-related cardiac dysfunction still remains a leading cause of cardiovascular death. Recent data have suggested that increases in cardiomyocyte apoptosis may be involved in the pathological remodeling of heart. Here, we examine the effects of aging on cardiomyocyte apoptosis in 6-, 30-, and 36-month-old Fischer344xBrown Norway F1 hybrid rats (F344XBN). Compared with 6-month hearts, aged hearts exhibited increased TdT-mediated dUTP nick end labeling–positive nuclei, caspase-3 activation, caspase-dependent cleavage of α-fodrin and diminished phosphorylation of protein kinase B/Akt (Thr 308). These age-dependent increases in cardiomyocyte apoptosis were associated with alterations in the composition of the cardiac dystrophin …
Dsarm/Sarm1 Is Required For Activation Of An Injury-Induced Axon Death Pathway, Jeannette Osterloh, Jing Yang, Timothy Rooney, A. Fox, Robert Adalbert, Eric Powell, Amy Sheehan, Michelle Avery, Rachel Hackett, Mary Logan, Jennifer Macdonald, Jennifer Ziegenfuss, Stefan Milde, Ying-Ju Hou, Carl Nathan, Aihao Ding, Robert Brown, Laura Comforti, Michael Coleman, Marc Tessier-Lavigne, Stephan Zuchner, Marc Freeman
Dsarm/Sarm1 Is Required For Activation Of An Injury-Induced Axon Death Pathway, Jeannette Osterloh, Jing Yang, Timothy Rooney, A. Fox, Robert Adalbert, Eric Powell, Amy Sheehan, Michelle Avery, Rachel Hackett, Mary Logan, Jennifer Macdonald, Jennifer Ziegenfuss, Stefan Milde, Ying-Ju Hou, Carl Nathan, Aihao Ding, Robert Brown, Laura Comforti, Michael Coleman, Marc Tessier-Lavigne, Stephan Zuchner, Marc Freeman
Dr Robert Brown
Axonal and synaptic degeneration is a hallmark of peripheral neuropathy, brain injury, and neurodegenerative disease. Axonal degeneration has been proposed to be mediated by an active autodestruction program, akin to apoptotic cell death; however, loss-of-function mutations capable of potently blocking axon self-destruction have not been described. Here, we show that loss of the Drosophila Toll receptor adaptor dSarm (sterile alpha/Armadillo/Toll-Interleukin receptor homology domain protein) cell-autonomously suppresses Wallerian degeneration for weeks after axotomy. Severed mouse Sarm1 null axons exhibit remarkable long-term survival both in vivo and in vitro, indicating that Sarm1 prodegenerative signaling is conserved in mammals. Our results provide direct …
Mitochondrial Antiviral Signaling Protein Defect Links Impaired Antiviral Response And Liver Injury In Steatohepatitis In Mice, Timea Csak, Angela Dolganiuc, Karen Kodys, Bharath Nath, Jan Petrasek, Shashi Bala, Dora Lippai, Gyongyi Szabo
Mitochondrial Antiviral Signaling Protein Defect Links Impaired Antiviral Response And Liver Injury In Steatohepatitis In Mice, Timea Csak, Angela Dolganiuc, Karen Kodys, Bharath Nath, Jan Petrasek, Shashi Bala, Dora Lippai, Gyongyi Szabo
Gyongyi Szabo
Mitochondrial dysfunction is a pathogenic feature of nonalcoholic steatohepatitis (NASH). NASH complicates hepatotropic viral disease. The mitochondrial antiviral signaling protein (MAVS) is the adapter of helicase receptors involved in sensing double-stranded RNA (dsRNA). We hypothesized that impaired MAVS function may contribute to insufficient antiviral response and liver damage in steatohepatitis. We identified reduced MAVS protein levels and increased MAVS association with the proteasome subunit alpha type 7 (PSMA7) in livers from mice given a methionine-choline-deficient (MCD) diet. Decreased association of MAVS with mitochondria and increased cytosolic cytochrome c indicated mitochondrial damage in steatohepatitis. In vivo administration of the synthetic dsRNA …
Fatty Acid And Endotoxin Activate Inflammasomes In Mouse Hepatocytes That Release Danger Signals To Stimulate Immune Cells, Timea Csak, Michal Ganz, Justin Pespisa, Karen Kodys, Angela Dolganiuc, Gyongyi Szabo
Fatty Acid And Endotoxin Activate Inflammasomes In Mouse Hepatocytes That Release Danger Signals To Stimulate Immune Cells, Timea Csak, Michal Ganz, Justin Pespisa, Karen Kodys, Angela Dolganiuc, Gyongyi Szabo
Gyongyi Szabo
The pathogenesis of nonalcoholic steatohepatitis (NASH) and inflammasome activation involves sequential hits. The inflammasome, which cleaves pro-interleukin-1beta (pro-IL-1beta) into secreted IL-1beta, is induced by endogenous and exogenous danger signals. Lipopolysaccharide (LPS), a toll-like receptor 4 ligand, plays a role in NASH and also activates the inflammasome. In this study, we hypothesized that the inflammasome is activated in NASH by multiple hits involving endogenous and exogenous danger signals. Using mouse models of methionine choline-deficient (MCD) diet-induced NASH and high-fat diet-induced NASH, we found up-regulation of the inflammasome [including NACHT, LRR, and PYD domains-containing protein 3 (NALP3; cryopyrin), apoptosis-associated speck-like CARD-domain containing …
Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana Akinsete, Gabriela Ion, Theodore Witte, W. Hardman
Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana Akinsete, Gabriela Ion, Theodore Witte, W. Hardman
Gabriela Ion
Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to …
Rsa 2004: Combined Basic Research Satellite Symposium - Session Three: Alcohol And Mitochondrial Metabolism: At The Crossroads Of Life And Death, Gyongyi Szabo, Jan Hoek, Victor Darley-Usmar, Gyorgy Hajnoczky, Thomas Knudsen, Daria Mochly-Rosen, Samir Zakhari
Rsa 2004: Combined Basic Research Satellite Symposium - Session Three: Alcohol And Mitochondrial Metabolism: At The Crossroads Of Life And Death, Gyongyi Szabo, Jan Hoek, Victor Darley-Usmar, Gyorgy Hajnoczky, Thomas Knudsen, Daria Mochly-Rosen, Samir Zakhari
Gyongyi Szabo
This article summarizes the proceedings of the RSA 2004 Combined Basic Research Satellite Meeting convened at the Westin Bayshore Resort and Marina, Vancouver, CA. One of the sessions "Alcohol and mitochondrial metabolism: At the crossroads of life and death" featured five speakers and was chaired by Drs. Jan Hoek and Sam Zakhari. The presentations were 1) Introduction: Alcohol and cellular energy metabolism by Jan Hoek, 2) Ethanol-dependent dysfunction of mitochondrial energy metabolism: the role of NO by Victor Darley-Usmar, 3) Ethanol and apoptosis in the heart by Gyorgy Hajnoczky, 4) Alcohol and mitochondrial biogenesis in development by Thomas Knudsen, and …
Liver In Sepsis And Systemic Inflammatory Response Syndrome, Gyongyi Szabo, Laszlo Romics, Gyorgy Frendl
Liver In Sepsis And Systemic Inflammatory Response Syndrome, Gyongyi Szabo, Laszlo Romics, Gyorgy Frendl
Gyongyi Szabo
In patients with sepsis and SIRS, the liver has two opposing roles: a source of inflammatory mediators and a target organ for the effects of the inflammatory mediators. The liver is pivotal in modulating the systemic response to severe infection, because it contains the largest mass of macrophages (Kupffer cells) in the body; these macrophages can clear the endotoxin and bacteria that initiate the systemic inflammatory response. This article summarizes the functional changes that take place in the liver during sepsis and systemic inflammatory response syndrome and discusses the cellular and molecular mechanisms that underlie clinical outcomes.
Hepatitis C Virus Ns5a Protein--A Master Regulator, Gyongyi Szabo
Hepatitis C Virus Ns5a Protein--A Master Regulator, Gyongyi Szabo
Gyongyi Szabo
No abstract provided.
Hepatitis C Virus Core And Nonstructural Protein 3 Proteins Induce Pro- And Anti-Inflammatory Cytokines And Inhibit Dendritic Cell Differentiation, Angela Dolganiuc, Karen Kodys, Andrea Kopasz, Christopher Marshall, Twan Do, Laszlo Romics, Pranoti Mandrekar, Maria Zapp, Gyongyi Szabo
Hepatitis C Virus Core And Nonstructural Protein 3 Proteins Induce Pro- And Anti-Inflammatory Cytokines And Inhibit Dendritic Cell Differentiation, Angela Dolganiuc, Karen Kodys, Andrea Kopasz, Christopher Marshall, Twan Do, Laszlo Romics, Pranoti Mandrekar, Maria Zapp, Gyongyi Szabo
Gyongyi Szabo
Antiviral immunity requires recognition of viral pathogens and activation of cytotoxic and Th cells by innate immune cells. In this study, we demonstrate that hepatitis C virus (HCV) core and nonstructural protein 3 (NS3), but not envelope 2 proteins (E2), activate monocytes and myeloid dendritic cells (DCs) and partially reproduce abnormalities found in chronic HCV infection. HCV core or NS3 (not E2) triggered inflammatory cytokine mRNA and TNF-alpha production in monocytes. Degradation of I-kappa B alpha suggested involvement of NF-kappa B activation. HCV core and NS3 induced production of the anti-inflammatory cytokine, IL-10. Both monocyte TNF-alpha and IL-10 levels were …