Gene expression in primary cultured astrocytes affected by aluminum: alteration of chaperons involved in protein folding
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : David A. Aremu Ojeiru F. Ezomo Shunsuke Meshitsuka
- چاپ و سال / کشور: 2010
Description
Objectives Aluminum is notorious as a neurotoxic metal. The aim of our study was to determine whether endoplasmic reticulum (ER) stress is involved in aluminuminduced apoptosis in astrocytes. Methods Mitochondrial RNA (mRNA) was analyzed by reverse transcription (RT)-PCR following pulse exposure of aluminum glycinate to primary cultured astrocytes. Tunicamycin was used as a positive control. Results Gene expression analysis revealed that Ire1b was up-regulated in astrocytes exposed to aluminum while Ire1a was up-regulated by tunicamycin. Exposure to aluminum glycinate, in contrast to tunicamycin, seemed to down-regulate mRNA expression of many genes, including the ER resident molecular chaperone BiP/Grp78 and Ca2?- binding chaperones (calnexin and calreticulin), as well as stanniocalcin 2 and OASIS. The down-regulation or nonactivation of the molecular chaperons, whose expressions are known to be protective by increasing protein folding, may spell doom for the adaptive response. Exposure to aluminum did not have any significant effects on the expression of Bax and Bcl2 in astrocytes. Conclusions The results of this study demonstrate that aluminum may induce apoptosis in astrocytes via ER stress by impairing the protein-folding machinery
Environ Health Prev Med (2011) 16:16–24 DOI 10.1007/s12199-010-0161-2 Received: 9 February 2010 / Accepted: 31 May 2010 / Published online: 22 June 2010
