http://www.healthcare.uiowa.edu/corefacilities/esr/publications/buettnerpubs/pdf/FRBM-2001-30-1191-FQS-Redox.pdf

Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple.

Infectious diseases of humans: Dynamics and control

The mitochondrial permeability transition.

The first suggestion that physical exercise results in free radical-mediated damage to tissues appeared in 1978, and the past three decades have resulted in a large growth of knowledge regarding exercise and oxidative stress. Although the sources of oxidant production during exercise continue to be debated, it is now well established that both resting and contracting skeletal muscles produce reactive oxygen species and reactive nitrogen species. Importantly, intense and prolonged exercise can result in oxidative damage to both proteins and lipids in the contracting myocytes. Furthermore, oxidants can modulate a number of cell signaling pathways and regulate the expression of multiple genes in eukaryotic cells. This oxidant-mediated change in gene expression involves changes at transcriptional, mRNA stability, and signal transduction levels. Furthermore, numerous products associated with oxidant-modulated genes have been identified and include antioxidant enzymes, stress proteins, DNA repair proteins, and mitochondrial electron transport proteins. Interestingly, low and physiological levels of reactive oxygen species are required for normal force production in skeletal muscle, but high levels of reactive oxygen species promote contractile dysfunction resulting in muscle weakness and fatigue. Ongoing research continues to probe the mechanisms by which oxidants influence skeletal muscle contractile properties and to explore interventions capable of protecting muscle from oxidant-mediated dysfunction.

/pdf/exercise-induced-oxidative-stress-cellular-mechanisms-and-4a18810890.pdf

Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production

Glutathione and its role in cellular functions.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840050529

Altered thiol and calcium homeostasis in oxidative hepatocellular injury

The intracellular distribution of glutathione (GSH) in cultured hepatocytes has been investigated by using the compound monochlorobimane (BmCl), which interacts specifically with GSH to form a highly fluorescent adduct. Image analysis of BmCl-labeled hepatocytes predominantly localized the fluorescence in the nucleus; the nuclear/cytoplasmic concentration gradient was approximately three. This concentration gradient was collapsed by treatment of the cells with ATP-depleting agents. The uneven distribution of BmCl fluorescence was not attributable to (i) nonspecific interaction of BmCl with protein sulfhydryl groups, (ii) any selective nuclear localization of the GSH transferase(s) catalyzing formation of the GSH-BmCl conjugate, or (iii) any apparent alterations in cell morphology from culture conditions, suggesting that this distribution did, indeed, reflect a nuclear compartmentalization of GSH. That the nuclear pool of GSH was found more resistant to depletion by several agents than the cytoplasmic pool supports the assumption that GSH is essential in protecting DNA and other nuclear structures from chemical injury.

https://www.pnas.org/content/pnas/89/10/4412.full.pdf

Demonstration of nuclear compartmentalization of glutathione in hepatocytes.

As tert-butyl hydroperoxide is metabolized by the glutatione peroxidase--glutathione reductase enzyme system present in liver mitochondria, rapid and extensive oxidation of NADH and slow NADPH oxidation are observed. This NAD(P)H oxidation can be prevented, or reversed, more effectively by 2-hydroxybutyrate than by isocitrate, indicating an important role of mitochondrial NAD(P)+ transhydrogenase activity in maintaining a high NADPH/NADP+ ratio for glutathione reductase. In Ca2+-loaded mitochondria tert-butyl hydroperoxide-induced NAD(P)H oxidation is followed by Ca2+ release from the mitochondria. If either 2-hydroxybutyrate or isocitrate is present, no Ca2+ release can be induced by the hydroperoxide. Following Ca2+ efflux the NAD(P)H oxidation process becomes irreversible and membrane damage occurs. These late effects do not take place if ruthenium red is added to prevent re-uptake of released Ca2+ by the mitochondria. Thus, we conclude that the metabolism of tert-butyl hydroperoxide leads to a release of mitochondrial Ca2+ via oxidation of pyridine nucleotides, and that subsequent membrane damage is not directly associated with this Ca2+ efflux but results from continued cycling of released Ca2+.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1984.tb08058.x

Pyridine-nucleotide oxidation, Ca2+ cycling and membrane damage during tert-butyl hydroperoxide metabolism by rat-liver mitochondria

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2890%2980040-P

Calcium-dependent DNA fragmentation in human synovial cells exposed to cold shock

The present study was undertaken to determine whether specific interactions between cAMP and glucocorticoids regulate apoptosis in thymocytes. Incubation of murine thymocytes with agents that eleva...

Sten Orrenius

Papers

Altered thiol and calcium homeostasis in oxidative hepatocellular injury

Demonstration of nuclear compartmentalization of glutathione in hepatocytes.

Pyridine-nucleotide oxidation, Ca2+ cycling and membrane damage during tert-butyl hydroperoxide metabolism by rat-liver mitochondria

Calcium-dependent DNA fragmentation in human synovial cells exposed to cold shock

Cyclic AMP potentiates glucocorticoid-induced endogenous endonuclease activation in thymocytes.