scholarly journals Oxidative Stress Increased Respiration and Generation of Reactive Oxygen Species, Resulting in ATP Depletion, Opening of Mitochondrial Permeability Transition, and Programmed Cell Death

2002 ◽  
Vol 128 (4) ◽  
pp. 1271-1281 ◽  
Author(s):  
Budhi Sagar Tiwari ◽  
Beatrice Belenghi ◽  
Alex Levine
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Mitochondrial Permeability Transition ◽  
Reactive Oxygen ◽  
Permeability Transition ◽  
Atp Depletion ◽  
Oxygen Species ◽  
Mitochondrial Permeability

Mitochondrial permeability transition in hepatocytes induced by t-BuOOH: NAD(P)H and reactive oxygen species

1997 ◽  
Vol 272 (4) ◽  
pp. C1286-C1294 ◽  
Author(s):  
A. L. Nieminen ◽  
A. M. Byrne ◽  
B. Herman ◽  
J. J. Lemasters
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Mitochondrial Permeability Transition ◽  
Reactive Oxygen ◽  
Permeability Transition ◽  
Cell Killing ◽  
Second Phase ◽  
Oxygen Species ◽  
Mitochondrial Permeability ◽  
Ros Formation

Tert-butyl hydroperoxide (t-BuOOH) induces the mitochondrial permeability transition (MPT) in hepatocytes, leading to cell death. Using confocal microscopy, we visualized pyridine nucleotide oxidation and reactive oxygen species (ROS) formation induced by t-BuOOH. Reduced mitochondrial pyridine nucleotides (NADH and NADPH) were imaged by autofluorescence. Mitochondrial membrane potential, ROS, onset of MPT, and cell death were monitored with tetramethylrhodamine methyl ester (TMRM), dichlorofluorescin, calcein, and propidium iodide, respectively. t-BuOOH rapidly oxidized mitochondrial NAD(P)H. Oxidation was biphasic, and the second slower phase occurred during mitochondrial ROS generation. Subsequently, MPT took place, mitochondria depolarized, and cells died. beta-Hydroxybutyrate, which reduces mitochondrial NAD+, delayed cell killing, but lactate, which reduces cytosolic NAD+, did not. Trifluoperazine, which inhibits MPT, did not block the initial oxidation of NAD(P)H but prevented the second phase of oxidation, partially blocked ROS formation, and preserved cell viability. The antioxidants, deferoxamine and diphenylphenylenediamine, also prevented the second phase of NAD(P)H oxidation. They also blocked ROS formation nearly completely and stopped cell killing. Both antioxidants also prevented the mitochondrial permeability transition and subsequent mitochondrial depolarization. In conclusion, NAD(P)H oxidation and ROS formation are critical events promoting MPT in oxidative injury and death of hepatocytes.

Apoptosis in Heart and Skeletal Muscle

2002 ◽  
Vol 27 (4) ◽  
pp. 349-395 ◽  
Author(s):  
Andy J. Primeau ◽  
Peter J. Adhihetty ◽  
David A. Hood
Keyword(s):  
Reactive Oxygen Species ◽  
Skeletal Muscle ◽  
Cell Death ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Permeability Transition ◽  
Current Evidence ◽  
Oxygen Species ◽  
Cellular Mechanisms

Apoptosis, or programmed cell death, is now recognized to be an important cellular event during normal development and in the progression of specific diseases. Apoptosis can be triggered by stimuli initiating outside of the cell, or within the mitochondria, leading to the activation of caspases and subsequent cell death. Although apoptosis has been widely studied in a variety of tissues over the last 5 years, skeletal muscle and heart have been relatively ignored in this regard. Research on apoptosis in cardiac muscle has recently taken on a higher profile as the recognition emerges that it may be an important contributor to specific cardiac pathologies, particularly in response to ischemia-reperfusion in which reactive oxygen species are formed. In skeletal muscle, very few studies have been done under specific physiological (e.g., exercise) and pathophysiological (e.g., dystrophies, denervation, myopathies) conditions. Skeletal muscle is unique in that it is mutli-nucleated, and evidence suggests that it can undergo individual myonuclear apoptosis as well as complete cell death. This review discusses the basic cellular mechanisms of apoptosis, as well as the current evidence of this process in cardiac and skeletal muscle. The need for more work in this area is highlighted, particularly in exercise and training. Key words: transcription factors, reactive oxygen species, mitochondria, caspase, mitochondrial permeability transition

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