Neonatal hypothyroidism alters the kinetic properties of Na+, K+-ATPase in synaptic plasma membranes from rat brain.

Neonatal hypothyroidism was induced in rat pups by injecting 131I within two days of birth and the effects on kinetic properties of Na+, K+-ATPase from synaptic plasma membranes were examined. Neonatal hypothyroidism resulted in a generalized decrease in V(max) with ATP, Na+, K+ and Mg2+ together with an increase in the K(m) for ATP, appearance of a low affinity component for Na+ and allosteric characteristic for the Mg2+-dependent activity at high Mg2+ concentrations. Binding pattern for Na+ and Mg2+ changed. Our results suggest that impairment of Na+, K+-ATPase activity together with altered kinetic properties could be one of the underlying biochemical mechanism leading to central nervous system (CNS) dysfunctions as a consequence of thyroid hormone deprivation during critical stages of brain development.

Insulin status differentially affects energy transduction in cardiac mitochondria from male and female rats.

AIM: The incidence of coronary heart diseases (CHD), congestive heart failure (CHF) and myocardial infarction is higher in diabetic patients than in non-diabetic groups, with these incidences being more in women than in the men. Hence, we examined involvement of mitochondrial energy transduction functions. METHODS: Mitochondrial energy metabolism in cardiomyopathy was studied using streptozotocin (STZ)-diabetic male and female rats as the model system. Effects of insulin treatment were also evaluated. RESULTS: The body and heart weights decreased in both male and female diabetic rats. Insulin treatments resulted in significant increase in the body and heart weights in the female rats. Mitochondrial respiration rates with all the substrates tested decreased in diabetic condition in both males and females. Treatment with two dose-regimens of insulin had differential restorative effect on mitochondrial substrate oxidation in the males but caused hyper-stimulation in the females. Diabetic state brought about 19% decrease in the cytochrome aa(3) content in the female rats. Treatment with 0.6 units of insulin significantly increased the cytochrome contents in general in both the sexes whereas higher dose (1.0 unit) caused decrease in the cytochromes content in the females. Diabetic state resulted in decreased dehydrogenases activities; insulin treatments had differential effect on the dehydrogenase activity in the males and the females. The results suggest that insulin treatment-induced hyper-stimulation of respiration in female rats may lead to increased production of reactive oxygen species. Besides, increased formation of advanced glycosylated end products may further lead to increased risk of CHF and CHD. CONCLUSIONS: The results suggest that differential effects of STZ-diabetes and insulin treatments in the female rats than in males may be the underlying cause for increased incidence of diabetic cardiomyopathies in the females.

Effect of neonatal hypothyroidism on Ca(2+)-ATPase activity in the rat brain.

Effect of neonatal hypothyroidism on kinetic properties of Ca(2+)-ATPase from rat brain synaptic plasma membranes and microsomes were examined. Neonatal hypothyroidism resulted in significant decrease in the enzyme activity in both the membrane systems. The synaptic membranes in control group displayed presence of one kinetic component whereas a low affinity component became evident in the hypothyroid group. In the microsomes, both control as well as hypothyroid groups showed presence of two kinetic components with the latter group showing two-fold increase in the K(m). The Ca(2+) binding characteristics were generally unaltered in the enzyme from both the membrane systems. Our results suggest that impairment in the Ca(2+)-ATPase activity together with altered kinetic properties could be one of the underlying biochemical mechanisms leading to CNS dysfunction as a consequence of thyroid hormone deprivation during critical stages of brain development.