Membrane Enzyme Development in Nerve Ending Mitochondria during Neonatal Hypothyroidism

Abstract

The effect of propylthiouracil-induced neonatal hypothyroidism on the development of synaptosome fraction mitochondrial membrane enzymes has been determined. Total and specific activities of two mitochondrial inner membrane (cytochrome c oxidase and succinate cytochrome c reductase) and two outer membrane enzymes (monoamine oxidase and rotenone-insensitive NADH cytochrome c reductase) were determined. The inner mitochondrial membrane enzymes developed in synchrony in euthyroid animals, but a decrease in fractional and specific activities of both inner membrane enzymes occurred in hypothyroidism. The outer membrane enzymes developed asynchronously; monoamine oxidase revealed a 9-fold increase while NADH cytochrome c reductase increased 4-fold. Hypothyroidism caused no change in total fractional activity or K_m and an increased specific activity of outer membrane enzymes.

Presence of Kynurenine Hydroxylase in Developing Rat Brain

“…rats, cytochrome c oxidase and succinate cytochrome c reductase exhibit the same maturational increase as the two outer mitochondrial enzymes. However they have decreased activities in hypothyroid fractions on day 14 (Battie and Verity, 1979). These data may indicate that the normal maturational increase of kynurenine hydroxylase and M A 0 is due to increased size or number of mitochondria while the hypothyroid-induced increase may be due to a change in the amount of individual enzyme per mitochondrion.…”

“…The change in activity of kynurenine hydroxylase attributable to maturation and hypothyroidism was investigated in synaptosomal fractions because mitochondria in these fractions may be from a homogenous population of mitochondria (Battie and Verity, 1979) compared to those from the mitochondrial fraction. The activity of kynurenine hydroxylase in synaptosomal fractions isolated from cerebral cortices of rats of two different ages is shown in Table 2, where this enzyme's activity is compared to that of MAO, another enzyme of the outer membrane of the mitochondria.…”

“…Rat pups were rendered hypothyroid by the administration of 6-propyl-3-thiouraci1 to their mothers from the day of birth (Battie and Verity, 1979). Crude mitochondrial pellets were obtained from the cerebral cortices of rats aged 8 and 14 days and were subjected to centrifugation on Ficoll-sucrose discontinuous gradients from which were obtained myelin (A), synaptosomal (B), and mitochondrial (C) fractions (Verity, 1972).…”

Content of Mitochondrial DNA and of Three Mitochondrial RNAs in Developing and Adult Rat Cerebellum

“…The loss of mtDNA in free (nonsynaptic) mitochondria of the adult rat cerebellum could be explained by the migration of mitochondria from the perikaryon toward the synaptic endings after the second week of life due to synaptogenesis which becomes very active at this time in rat cerebellum (Gombos et al, 1980). Indeed, a threefold increase in the total activity of cytochrome c oxidase and succinate cytochrome c reductase in the synaptosomal fraction of developing cerebellum of rats of 7 and 14 days of age was reported by Battie and Verity (1979). As far as the steady-state level of the three mtRNAs studied in free (nonsynaptic) mitochondria, an accumulation of each species takes place in developing rat cerebellum as can be calculated from the data reported in Tables 1 and 2.…”

Differential effect of thyroid hormone deficiency on the growth of calretinin-expressing neurons in rat spinal cord and dorsal root ganglia

“…The final PTU dosage used in the present study was selected from different doses (0.0001-0.5%) tested in our laboratory according to previous studies (Legrand, 1967(Legrand, , 1986Battie and Verity, 1979;Narayanan et al, 1986;Lomax and Robertson, 1992). These pregnant dams were kept in individual cages and fed with standard cube diet.…”