Hypoxia cellular mechanisms

Prabhakar NR. Physiological and genomic consequences of intermittent hypoxia— Invited review Oxygen sensing during intermittent hypoxia cellular and molecular mechanisms. J Appl Physiol 2001 90 1986-1994. 

IV. Cellular Mechanisms Underlying the Neuronal Responses to Hypoxia... 

As the AO with a direct nonspecific mechanism of action we have chosen Hypoxene - sodium poly(2,5-dihydroxiphenyl)-4-thiosulfonate. Besides a direct AO effect as a scavenger of free radicals it exerts an anti-hypoxic effect shunting I and II complexes of mitochondrial respiratory chain, which are inhibited as a consequence of hypoxia (Eropkin et al., 2007). Hypoxene was introduced into cell incubation media before illumination and left during cells further incubation. Hypoxene in the concentration of 40pg/ml, comparable to doses applied in vivo, completely blocked C60-induced phototoxicity (Table 7.3). Cellular viability has completely recovered to control level, which is a convincing evidence of free radical nature of cellular damage in photodynamic effect of fullerene. 

Acute exposure of Chinese hamster ovary (CHO) cells or human bladder cancer MGH-U1 cells to hypoxia plus low pH (6.5-6.0), was cytotoxic in a time- and pH-dependent manner. Inhibition of glycolysis by incubation of CHO cells under hypoxic conditions in the absence of glucose at pH 7.0 led to a larger fall in cellular ATP and energy charge. A decrease in energy charge of the cells may contribute to loss of viability, but additional mechanisms appear to be involved (Rotin et al., 1986). 

The Na /K ATPase is the main active transport mechanism responsible for maintaining ionic homeostasis, and this process involves continuous expenditure of ATP. Normal cell volume depends on the constant extrusion of intracellular Na by the Na /K ATPase. Ischemia/hypoxia results in abrogation of mitochondrial oxidative phosphorylation, and a rapid loss of ATP compromising the cellular ionic homeostasis. Sodium ion influx drives Cl influx via chloride channels, resulting in an increased osmolarity inside the cell that drives inflow of water mainly via AQP channels (Badaut et al., 2002 Amiry-Moghaddam and Ottersen, 2003 Liang et al.,... 

Adiponitrile s mechanism of toxicity is similar to cyanide because it can potentially liberate cyanide in the body spontaneously. It forms a stable complex with ferric iron in the cytochrome oxidase enzymes, thereby inhibiting cellular respiration. Cyanide affects primarily the central nervous system (CNS), producing early stimulation followed by depression. It initially stimulates the peripheral chemoreceptors (causing increased respiration) and the carotid bodies (thereby slowing the heart). Early CNS, respiratory, and myocardial depression result in decreased oxygenation of the blood and decreased cardiac output. These effects produce both stagnation and hypoxemic hypoxia in addition to cytotoxic hypoxia from inhibition of mitochondrial cytochrome oxidase. 

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