The non-protein thiol of rat liver mitochondria

Kamminga, A.

doi:10.1016/0304-4165(74)90099-3

Cited by 75 publications

(26 citation statements)

References 20 publications

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“…GSH/GSSG ratios are not in equilibrium with each other in mitochondria, nucleus, the secretory pathway and the extracellular space[36]. Mitochondrial GSH is responsible for 15% to 30% of total GSH[37]. In the ER, the GSH/GSSG ratio ranges between 3/1 and 1/1.…”

Section: Endogenous Antioxidant Defense System In the Gutmentioning

confidence: 99%

Oxidative stress, antioxidants and intestinal calcium absorption

Barboza¹,

Guizzardi²,

Moine³

et al. 2017

WJG

107

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The disequilibrium between the production of reactive oxygen (ROS) and nitrogen (RNS) species and their elimination by protective mechanisms leads to oxidative stress. Mitochondria are the main source of ROS as by-products of electron transport chain. Most of the time the intestine responds adequately against the oxidative stress, but with aging or under conditions that exacerbate the ROS and/or RNS production, the defenses are not enough and contribute to developing intestinal pathologies. The endogenous antioxidant defense system in gut includes glutathione (GSH) and GSH-dependent enzymes as major components. When the ROS and/or RNS production is exacerbated, oxidative stress occurs and the intestinal Ca2+ absorption is inhibited. GSH depleting drugs such as DL-buthionine-S,R-sulfoximine, menadione and sodium deoxycholate inhibit the Ca2+ transport from lumen to blood by alteration in the protein expression and/or activity of molecules involved in the Ca2+ transcellular and paracellular pathways through mechanisms of oxidative stress, apoptosis and/or autophagy. Quercetin, melatonin, lithocholic and ursodeoxycholic acids block the effect of those drugs in experimental animals by their antioxidant, anti-apoptotic and/or anti-autophagic properties. Therefore, they may become drugs of choice for treatment of deteriorated intestinal Ca2+ absorption under oxidant conditions such as aging, diabetes, gut inflammation and other intestinal disorders.

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Section: Endogenous Antioxidant Defense System In the Gutmentioning

confidence: 99%

Oxidative stress, antioxidants and intestinal calcium absorption

Barboza¹,

Guizzardi²,

Moine³

et al. 2017

WJG

107

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“…20 and 23-27), and there is evidence for at least two pools of intracellular GSH (20,24,(27)(28)(29)(30). Previous studies were interpreted to indicate that there is a separate pool of GSH in mitochondria, that mitochondrial GSH does not equilibrate with cytoplasmic GSH, that the mitochondrial membrane is impermeable to GSH, and that mitochondrial GSH is synthesized in situ (22,(27)(28)(29)(30). In studies in which isolated hepatocytes were treated with diethyl maleate, no depletion of mitochondrial GSH was observed, whereas substantial depletion of cytoplasmic GSH was found, and it was concluded that the mitochondrial pool in the isolated hepatocyte is metabolically separate from that in the cytoplasm (27).…”

Section: Discussionmentioning

confidence: 99%

Origin and turnover of mitochondrial glutathione.

Griffith¹,

Meister²

1985

Proc. Natl. Acad. Sci. U.S.A.

442

255

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Mitochondrial glutathione in liver does not arise by intramitochondrial synthesis, but rather from the cytoplasm, by a process characterized by slow net transport and more rapid exchange transport.Glutathione (GSH) biosynthesis is specifically inhibited by buthionine sulfoximine, a mechanism-based inhibitor ofglutamylcysteine synthetase (1, 2). After administration of this compound, GSH is rapidly depleted from many cells and tissues because it continues to be used by various transport and metabolic processes. Previous experiments showed that the levels ofGSH in the liver and kidney ofmice given a single dose of buthionine sulfoximine decrease within 30-60 min to values that are 15-20% of those of untreated controls. Further decrease of the GSH levels occurs much more slowly even if additional buthionine sulfoximine is administered. In contrast, similar studies with higher homologs of buthionine sulfoximine (hexathionine sulfoximine and heptathionine sulfoximine) showed rapid and virtually complete disappearance of GSH from both liver and kidney (2).The present work elucidates the biphasic disappearance of GSH after administration of buthionine sulfoximine. Previous findings suggested that a separate pool of GSH is sequestered in certain cell types or within cell organelles. The observation that mitochondrial GSH decreases much more slowly than total tissue GSH after buthionine sulfoximine administration (3) suggested that there is a separate mitochondrial pool of GSH. However, since injected buthionine sulfoximine does not readily penetrate into mitochondria (3), it is possible that mitochondrial GSH synthesis occurs but is protected from inhibition by this transport barrier. The present studies exclude this interpretation. We have also examined the rates of incorporation of radiolabel from [35S]cyst(e)ine into cytoplasmic and mitochondrial GSH and have found that these rates are similar. EXPERIMENTAL PROCEDURESMaterials. Reagents used for the isolation of mitochondria and for the assay of enzymes and GSH were obtained from Sigma. Monobromobimane Methods. Isolation of cytoplasmic and mitochondrial fractions for enzyme studies. Mitochondria were isolated from the livers of fed rats by the procedure of Greenawalt (6). The isolation medium (200 mM D-mannitol/70 mM sucrose/2 mM K+ Hepes, pH 7.4) did not contain bovine serum albumin but was supplemented with 5 mM 5-oxo-L-proline for studies of 5-oxoprolinase. The livers of 2 rats (24-27 g of tissue) yielded -2 ml of mitochondrial pellet, which contained 50-60% of the citrate synthase activity (7) of the whole liver homogenate. The mitochondrial wash solutions contained no citrate synthase, indicating that matrix enzymes remained sequestered in the isolated mitochondria. Examination of the mitochondrial pellet by electron microscopy showed intact and generally wellpreserved mitochondria (>90%) as well as some small vesicles and lysosomes. For enzyme studies, isolated mitochondria were suspended in 1 ml of isolation medium and sonicated (Branson model W185D,...

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“…Animal mitochondria (60)(61)(62)(63)(64)(65)(66) and plant chloroplasts (67)(68)(69)(70) have been shown to contain pools of glutathione that are distinct from the cytoplasmic pools. Since these organelles are the key sites of oxygen utilization and oxygen production in eukaryotes, it is important to understand the origin of the glutathione in these pools.…”

Section: F Gsh Synthesis In Mitochondria and Chloroplastsmentioning

confidence: 99%