신경계 손상에서의 Star D6의 반응

Abstract

Neurosteroids are known to have neuroprotective properties and the steroidogenic acute regulatory protein (StAR)-mediated delivery of cholesterol is rate limiting in steroidogenesis. StAR belongs to a family of 15 StAR-related lipid transfer (START) domain containing proteins termed StAR/StarD1 ~ StarD15. StarD6, particularly, is known to be confined in male germ cells and thus exhibits a role in spermatogenesis. The presence of StarD6 in the rat brain was recently demonstrated by immunohistochemistry, although StAR distributed ubiquitously. Here I present a new additional evidence of StarD6 as a regulatory protein in neurosteroid synthesis following neurodegenerative stimuli. The temporal lobe epilepsy was induced by pilocarpine (350 mg/kg, intraperitoneally), and convulsive reactions were observed. On scheduled time the hippocampus was removed and examined by immunohistochemistry and Western blot analysis. In control group, StAR appeared in the cytoplasm of the strata oriens and radiatum and in the granular layer, while StarD6 was seen in the cytoplasm as well as in the nuclei of the stratum pyramidale and in the granular layer. StAR and StarD6 immunolocalization was increased following the epilepsy. StAR immunolocalization was seen not only in the strata oriens and radiatum but also in the stratum pyramidale from 3 h until 24h after epilepsy. StarD6 immunolocalization was seen in the stratum lacunosum-moleculare as well as in the stratum pyramidale from 3 h until 12 h after epilepsy. Moreover, the level of StarD6 protein was acutely and transiently elevated at 3 h following pilocarpine-treated rat hippocampus comparing with normal rats. These results on StAR is generally consistent with the previous report, but the target area after epilepsy was the stratum pyramidale of hippocampus in this study. Nuclear localization and transiently elevated level of StarD6 raises the possibility as a regulatory protein in neurosteroidogenesis and suggests that subsequent formations of neuroprotective steroids may be part of the mechanism used by the brain to cope with neurodegenerative diseases.