Modulation of succinate dehydrogenase in response to environmental stress conditions of hypobaria and hypoxia

Abstract

1. 1. An increase in the oxidation of succinate by hepatic mitochondria in rats exposed to hypoxia (O 2-N 2; 1:9, v/v) or hypobaria (0.5 atm) was observed which appears to be due to modification of the activity of the rate-limiting succinate dehydrogenase [succinate: (acceptor) oxidoreductase, EC 1.3.99.1]. 2. 2. The qualitative nature of this increase was indicated by obtaining the same maximal activity in both control and the exposed groups on activation by preincubation of such mitochondria with succinate and also by the failure to prevent the changes on treatment of the animals during the exposure to stress with the protein-synthesis inhibitor cycloheximide. 3. 3. The increase in enzyme activity was progressive with the time of exposure and reached a maximum by 4 h and was maintained at this high level under hypoxia for 36 h but reverted to the basal level under hypobaria by 12 h. On withdrawal of the stress at 4 h the activity reverted to the basal level in 6 h after hypobaric stress and in 12 h in hypoxic stress. 4. 4. The increased activity was stable to repeated washing in vitro of such mitochondria with the sucrose homogenizing medium. A similar washing procedure after preincubation with succinate, which may displace a firmly bound effector, however, reversed the hypoxic activation but not the hypobaric activation. 5. 5. Although succinate neotetrazolium reductase measures the same flavo-protein, activity assayed by this method showed no changes except for the significant increase at long exposure of 36 h only under hypoxia. 6. 6. The results suggest that the modulation of the succinate debydrogenase activity in hypobaria and hypoxia appears to be a compensatory mechanism invoked to overcome the effect of lowered O 2 tension prevalent in both the stress conditions.