Effect of thyroid deficiency on Go alpha-subunit isoforms in developing rat cerebral cortex.
Postnatal development of G alpha o isoforms in rat cerebral cortex was studied by SDS-PAGE and immunoblotting. When rat cerebral cortical membranes were resolved on separating gels containing 9% acrylamide and 8 M urea, three electrophoretically distinct G alpha o-immunoreactive proteins were evident. Comparison of their electrophoretic mobilities and partial tryptic digest pattern with recombinant G alpha o1 or G alpha o1-specific antibody revealed that the slowest and intermediate-migrating bands represent unmodified and fatty acylated forms of G alpha o1 protein, respectively. The fastest-migrating band corresponds to G alpha o2. While the fatty acylated form of G alpha o1 is the predominant species, its appearance paralleled that observed for G alpha o2 in developing rat cortex. Perinatal hypothyroidism induced by methimazole treatment did not significantly alter the appearance of cerebral cortical G alpha o1 and G alpha o2 between days 1 and 22 postpartum. Our findings support the earlier idea that heterogeneity of G alpha o proteins in mammalian brain is likely the result of different co- or post-translational processings of each splice variant of G alpha o. While the appearance of G alpha o isoforms is developmentally regulated, they likely do not play an obligatory role in neonatal brain development. Alternatively, the expression of G alpha o isoforms in developing rat cortex may be controlled by an intrinsic signal(s) that is independent of the thyroid status.
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Section of Biochemical Psychiatry, Clarke Institute of Psychiatry, University of Toronto, Ontario, Canada.
Andreopoulos
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Wong
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Vecil
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Warsh
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D000595:Amino Acid Sequence; D000818:Animals; D002540:Cerebral Cortex / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005314:Embryonic and Fetal Development / Q000502:physiology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007037:Hypothyroidism / Q000378:metabolism*; D008969:Molecular Sequence Data; D051381:Rats; D017208:Rats, Wistar; D013963:Thyroid Hormones / Q000502:physiology
D013963:Thyroid Hormones; D019204:GTP-Binding Proteins