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One or more keywords matched the following properties of Lemasters, John
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overview I have a long-standing interest in hepatic ischemia-reperfusion (IR) injury, especially as it relates to organ preservation for transplantation. I and my colleagues were the first to show a prominent role for nonparenchymal cells in IR injury to cold-stored livers. Specifically, we showed that reperfusion after cold ischemic storage leads to killing of sinusoidal endothelial cells and activation of Kupffer cells. We were also pioneers in showing that onset of the mitochondrial permeability transition (MPT) then developed in hepatic parenchymal cells, leading to hepatic apoptosis, necrosis and graft failure, and we developed a variety of stratagems to ameliorate these injuries that are beginning to find clinical application. Overall, my laboratory has published over 350 papers in peer-reviewed journals plus more than 100 book chapters. Productive, long-term collaborations with both junior and senior colleagues contributed importantly to this success. My research interests continue to relate to mitochondrial and cellular bioenergetics, including studies of oxidative phosphorylation in isolated mitochondria, mitochondrial dysfunction in toxic, and hypoxic and reperfusion injury to liver and heart cells, and graft failure from preservation injury to livers stored for transplantation surgery. Our in vitro and in vivo studies of living cells and tissues have shown that mitochondrial calcium uptake, iron translocation from lysosomes to mitochondria, and oxidative stress promote the MPT. The MPT initially induces lysosomal degradation of mitochondria by autophagy, a selective process called mitophagy. However, excess MPT induction induces both necrotic cell death from ATP depletion and apoptosis due to cytochrome c release after mitochondrial swelling. For these projects, my laboratory extensively applies new techniques of quantitative laser scanning confocal and intravital multiphoton microscopy for physiological analysis of single cells and living organs. The lab also extensively employs Seahorse technology to measure respiration and glycolytic flux in cultured cells. Current projects are examining how iron mobilization from lysosomes to cytosol and then to mitochondria during cold ischemic liver storage sensitizes hepatocytes and nonparenchymal cells to adverse events after reperfusion, leading ultimately to injury and failure of liver grafts. Despite a detailed understanding of their metabolism, mitochondria often behave anomalously. In particular, global suppression of mitochondrial metabolism and metabolite exchange occurs in apoptosis, ischemia/hypoxia, alcoholic liver disease and aerobic glycolysis in cancer cells (Warburg effect). My lab is also examining and supporting the novel hypothesis that closure of voltage-dependent anion channels (VDAC) in the mitochondrial outer membrane accounts for global mitochondrial suppression consistent with a role for VDAC as a dynamic regulator, or governator, of global mitochondrial function both in health and disease. In cancer cells, we showed that free tubulin causes closure of VDAC.
One or more keywords matched the following items that are connected to Lemasters, John
Item TypeName
Academic Article Mitochondrial permeability transition in pH-dependent reperfusion injury to rat hepatocytes.
Academic Article Role of the mitochondrial permeability transition in salicylate toxicity to cultured rat hepatocytes: implications for the pathogenesis of Reye's syndrome.
Academic Article The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy.
Academic Article Lipopolysaccharide-stimulated TNF-alpha release from cultured rat Kupffer cells: sequence of intracellular signaling pathways.
Academic Article Effects of chronic ethanol exposure on oxidation and NMDA-stimulated neuronal death in primary cortical neuronal cultures.
Academic Article Mitochondrial dysfunction and cytoskeletal disruption during chemical hypoxia to cultured rat hepatic sinusoidal endothelial cells: the pH paradox and cytoprotection by glucose, acidotic pH, and glycine.
Academic Article LPS receptor CD14 participates in release of TNF-alpha in RAW 264.7 and peritoneal cells but not in kupffer cells.
Academic Article The mitochondrial permeability transition is required for tumor necrosis factor alpha-mediated apoptosis and cytochrome c release.
Academic Article The mitochondrial permeability transition augments Fas-induced apoptosis in mouse hepatocytes.
Academic Article Molecular cloning and characterization of a human mitochondrial ceramidase.
Academic Article Mitochondrial calcium transients in adult rabbit cardiac myocytes: inhibition by ruthenium red and artifacts caused by lysosomal loading of Ca(2+)-indicating fluorophores.
Academic Article Effects of NMDA and ferrous sulfate on oxidation and cell death in primary neuronal cultures.
Academic Article NF-kappaB stimulates inducible nitric oxide synthase to protect mouse hepatocytes from TNF-alpha- and Fas-mediated apoptosis.
Academic Article Activated Kupffer cells cause a hypermetabolic state after gentle in situ manipulation of liver in rats.
Academic Article A superfusion system to study border zones in confluent cultures of neonatal rat heart cells.
Academic Article The mitochondrial permeability transition mediates both necrotic and apoptotic death of hepatocytes exposed to Br-A23187.
Academic Article Biliary excretion in primary rat hepatocytes cultured in a collagen-sandwich configuration.
Academic Article Mitochondrial permeability transition in the switch from necrotic to apoptotic cell death in ischemic rat hepatocytes.
Academic Article Confocal imaging of Ca2+, pH, electrical potential, and membrane permeability in single living cells.
Academic Article Bid activates multiple mitochondrial apoptotic mechanisms in primary hepatocytes after death receptor engagement.
Academic Article Protection by acidotic pH against anoxia/reoxygenation injury to rat neonatal cardiac myocytes.
Academic Article Discrimination of depolarized from polarized mitochondria by confocal fluorescence resonance energy transfer.
Academic Article A pH-dependent phospholipase A2 contributes to loss of plasma membrane integrity during chemical hypoxia in rat hepatocytes.
Academic Article Suppression of Ca2+ oscillations in cultured rat hepatocytes by chemical hypoxia.
Academic Article Mitochondrial permeability transition in acetaminophen-induced necrosis and apoptosis of cultured mouse hepatocytes.
Academic Article A novel cytotoxicity screening assay using a multiwell fluorescence scanner.
Academic Article Recovery of cultured rat neonatal myocytes from hypercontracture after chemical hypoxia.
Academic Article Tracker dyes to probe mitochondrial autophagy (mitophagy) in rat hepatocytes.
Academic Article Basal reactive oxygen species determine the susceptibility to apoptosis in cirrhotic hepatocytes.
Academic Article Proinflammatory kupffer cell alterations after femur fracture trauma and sepsis in rats.
Academic Article Role of apoptosis in acetaminophen hepatotoxicity.
Academic Article Multiparameter digitized video microscopy of toxic and hypoxic injury in single cells.
Academic Article Ethanol exposure decreases mitochondrial outer membrane permeability in cultured rat hepatocytes.
Academic Article Mechanisms of hepatotoxicity.
Academic Article Protection by acidotic pH and fructose against lethal injury to rat hepatocytes from mitochondrial inhibitors, ionophores and oxidant chemicals.
Academic Article Roles of mitophagy and the mitochondrial permeability transition in remodeling of cultured rat hepatocytes.
Academic Article Cytosolic free magnesium, ATP and blebbing during chemical hypoxia in cultured rat hepatocytes.
Academic Article [The role of the voltage-dependent anion channels in the outer membrane of mitochondria in the regulation of cellular metabolism].
Academic Article Mitochondrial degradation by autophagy (mitophagy) in GFP-LC3 transgenic hepatocytes during nutrient deprivation.
Academic Article Mitophagy selectively degrades individual damaged mitochondria after photoirradiation.
Academic Article Intracellular pH during "chemical hypoxia" in cultured rat hepatocytes. Protection by intracellular acidosis against the onset of cell death.
Academic Article Swelling, reductive stress, and cell death during chemical hypoxia in hepatocytes.
Academic Article Extracellular acidosis delays onset of cell death in ATP-depleted hepatocytes.
Academic Article NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis.
Academic Article A cytotoxicity assay for tumor necrosis factor employing a multiwell fluorescence scanner.
Academic Article The pH paradox in the pathophysiology of reperfusion injury to rat neonatal cardiac myocytes.
Academic Article Distribution of electrical potential, pH, free Ca2+, and volume inside cultured adult rabbit cardiac myocytes during chemical hypoxia: a multiparameter digitized confocal microscopic study.
Academic Article Suppression of lipopolysaccharide-stimulated release of tumor necrosis factor by adenosine: evidence for A2 receptors on rat Kupffer cells.
Academic Article Intracellular pH and Ca2+ homeostasis in the pH paradox of reperfusion injury to neonatal rat cardiac myocytes.
Academic Article Measurement of electrical potential, pH, and free calcium ion concentration in mitochondria of living cells by laser scanning confocal microscopy.
Academic Article Cyclosporin A delays mitochondrial depolarization induced by N-methyl-D-aspartate in cortical neurons: evidence of the mitochondrial permeability transition.
Academic Article Endocytosis and Ca2+ are required for endotoxin-stimulated TNF-alpha release by rat Kupffer cells.
Academic Article Protection by Carolina rinse solution, acidotic pH, and glycine against lethal reperfusion injury to sinusoidal endothelial cells of rat livers stored for transplantation.
Academic Article Role of ICE-like proteases in endothelial cell hypoxic and reperfusion injury.
Academic Article Use of a multiwell fluorescence scanner with propidium iodide to assess NMDA mediated excitotoxicity in rat cortical neuronal cultures.
Academic Article Mitochondrial permeability transition in hepatocytes induced by t-BuOOH: NAD(P)H and reactive oxygen species.
Academic Article Hepatitis C virus core and nonstructural proteins induce fibrogenic effects in hepatic stellate cells.
Academic Article Rusty notions of cell injury.
Academic Article Adaptive Kupffer cell alterations after femur fracture trauma in rats.
Academic Article Acetaminophen-induced oxidant stress and cell injury in cultured mouse hepatocytes: protection by N-acetyl cysteine.
Academic Article Nitric oxide protects rat hepatocytes against reperfusion injury mediated by the mitochondrial permeability transition.
Academic Article Cytosolic free Ca2+ and proteolysis in lethal oxidative injury in endothelial cells.
Academic Article Carolina rinse solution protects adenosine triphosphate-depleted hepatocytes against lethal cell injury.
Academic Article Reactive oxygen species, but not Ca2+ overloading, trigger pH- and mitochondrial permeability transition-dependent death of adult rat myocytes after ischemia-reperfusion.
Academic Article Nuclear translocation of endonuclease G and apoptosis-inducing factor during acetaminophen-induced liver cell injury.
Academic Article Toxic injury from mercuric chloride in rat hepatocytes.
Academic Article Opioid receptor-independent protection of ischemic rat hepatocytes by morphine.
Academic Article Is there release of mitochondrial calcium in toxic injury?
Academic Article The oxygen tension modulates acetaminophen-induced mitochondrial oxidant stress and cell injury in cultured hepatocytes.
Academic Article Inhibition of the mitochondrial permeability transition by protein kinase A in rat liver mitochondria and hepatocytes.
Academic Article Effect of short-term ethanol treatment on voltage-dependent calcium channels in Kupffer cells.
Academic Article Changes in shape and viability of cultured adult rabbit cardiac myocytes during ischemia/reperfusion injury.
Academic Article Progression of subcellular changes during chemical hypoxia to cultured rat hepatocytes: a laser scanning confocal microscopic study.
Academic Article ATP depletion rather than mitochondrial depolarization mediates hepatocyte killing after metabolic inhibition.
Academic Article Comparison of peptidoglycan-polysaccharide and lipopolysaccharide stimulation of Kupffer cells to produce tumor necrosis factor and interleukin-1.
Academic Article Mitochondria as a source of reactive oxygen species during reductive stress in rat hepatocytes.
Academic Article Inhibition of tumor necrosis factor release from cultured rat Kupffer cells by agents that reduce graft failure from storage injury.
Academic Article Mitochondrial and glycolytic dysfunction in lethal injury to hepatocytes by t-butylhydroperoxide: protection by fructose, cyclosporin A and trifluoperazine.
Academic Article Down-regulation of HCW9 mRNA in rat hepatocytes during chemical hypoxia involves both transcriptional and posttranscriptional mechanisms.
Academic Article Mitochondrial free calcium transients during excitation-contraction coupling in rabbit cardiac myocytes.
Academic Article Contribution of pH-dependent group II phospholipase A2 to chemical hypoxic injury in rat hepatocytes.
Concept Tumor Cells, Cultured
Concept Cells, Cultured
Academic Article ADAM17 promotes proliferation of collecting duct kidney epithelial cells through ERK activation and increased glycolysis in polycystic kidney disease.
Academic Article Translocation of iron from lysosomes to mitochondria during acetaminophen-induced hepatocellular injury: Protection by starch-desferal and minocycline.
Academic Article Effect of surface-potential modulators on the opening of lipid pores in liposomal and mitochondrial inner membranes induced by palmitate and calcium ions.
Academic Article Compartmentation of Mitochondrial and Oxidative Metabolism in Growing Hair Follicles: A Ring of Fire.
Academic Article Acid sphingomyelinase promotes mitochondrial dysfunction due to glutamate-induced regulated necrosis.
Academic Article Suppression of iron mobilization from lysosomes to mitochondria attenuates liver injury after acetaminophen overdose in vivo in mice: Protection by minocycline.
Academic Article A new fluorescent sensor mitoferrofluor indicates the presence of chelatable iron in polarized and depolarized mitochondria.
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