title: Gene expression in primary cultured astrocytes affected by aluminum: alteration of chaperons involved in protein folding.
abstract: OBJECTIVE
  Aluminum is notorious as a neurotoxic metal. The aim of our study was to determine whether endoplasmic reticulum (ER) stress is involved in aluminum-induced 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 Ire1β was up-regulated in astrocytes exposed to aluminum while Ire1α 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 Ca(2+)-binding chaperones (calnexin and calreticulin), as well as stanniocalcin 2 and OASIS. The down-regulation or non-activation 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.
authors: Division of Integrative Bioscience, Institute for Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago, Tottori, 683-8503, Japan.
authors: David A
authors: DA
authors: Aremu
authors: Ojeiru F
authors: OF
authors: Ezomo
authors: Shunsuke
authors: S
authors: Meshitsuka
mesh_terms: D000536:Aluminum Hydroxide / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D004722:Endoribonucleases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D005998:Glycine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism; D017510:Protein Folding / Q000187:drug effects*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012313:RNA / Q000187:drug effects; D000077278:RNA, Mitochondrial; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014415:Tunicamycin / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717248:Hspa5 protein, mouse; D018832:Molecular Chaperones; D011518:Proto-Oncogene Proteins; D000077278:RNA, Mitochondrial; D014415:Tunicamycin; D000536:Aluminum Hydroxide; D012313:RNA; C007420:dihydroxyaluminum aminoacetate; D004722:Endoribonucleases; D005998:Glycine