Protein kinase cα is involved in impaired perinatal hypothyroid rat brain development. Issue 2 (14th November 2012)

• Record Type: Journal Article
• Authors: Zhang, Hong‐Mei; Lin, Ning; Dong, Yan; Su, Qing; Luo, Min
• Is Part Of: Journal of neuroscience research. Volume 91:Issue 2(2013:Feb.)
• Page Start: 211
• Page End: 219
• Publication Date: 2012-11-14
• Subjects: Neurobiology -- Periodicals; 612
• DOI: 10.1002/jnr.23125
• Languages: English
• ISSNs: 0360-4012

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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. © 2012 Wiley Periodicals, Inc.</p> </abstract>