title: Protein kinase Cα is involved in impaired perinatal hypothyroid rat brain development.
abstract: Protein kinase Cα (PKCα) has been implicated in the regulation of a variety of cellular functions, such as proliferation, differentiation, and apoptosis, in response to a diverse range of stimuli. Activated PKCα mediates oxidative stress, apoptosis, and inflammatory reaction. Thyroid hormone (TH) is essential for the proper development of the mammalian central nervous system. TH deficiency during critical periods of brain development results in permanent cognitive and neurological impairments. In the present study, we attempted to explore whether PKCα is involved in impaired brain function in developing hypothyroid rat brain. Severe perinatal hypothyroidism was obtained by administration of 30 mg/day propylthiouracil to dams. Brain PKC activity in hypothyroid pups was increased significantly in cytosol and membrane fractions. The change of membrane PKC activity was more marked than that of cytosol, and hypothyroidism led to a higher ratio of membrane PKC activity to that in cytosol, which means abnormal activation of PKC in developing hypothyroid rat brain. Thyroxine replacement partially corrected these changes. After being treated with bisindolmaleimide XI, a mainly selective inhibitor for PKCα, the hypothyroid pups showed improved place navigation test results, and further Western blot analysis showed that PKCα expression in cytosol fractions was increased in hypothyroid rat brain with or without bisindolmaleimide XI treatment, but, after treatment with bisindolmaleimide XI, PKCα content in membrane fractions decreased almost to normal. Therefore, we conclude that PKCα appears to be involved in the impaired brain development observed in perinatal hypothyroid rat brain.
authors.affiliation: Department of Endocrinology, Xin Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Zhang
authors.forename: Ning
authors.initials: N
authors.lastname: Lin
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
authors.forename: Qing
authors.initials: Q
authors.lastname: Su
authors.forename: Min
authors.initials: M
authors.lastname: Luo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D013956:Antithyroid Agents / Q000633:toxicity; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000201:enzymology* / Q000254:growth & development* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007037:Hypothyroidism / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D018782:Maze Learning / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000503:physiopathology*; D011441:Propylthiouracil / Q000633:toxicity; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013974:Thyroxine / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D013956:Antithyroid Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D011441:Propylthiouracil; D051571:Protein Kinase C-alpha; C088060:bisindolylmaleimide; D013974:Thyroxine