Homocysteine induces X-box-binding protein 1 splicing in the mice brain.
Increasing evidence has been suggested that hyperhomocysteinemia is a risk factor of neurodegenerative diseases, although, the underlying mechanisms have not been elucidated. Here, we found peripheral application of homocysteine increases X-box-binding protein 1 (XBP1) splicing in the several areas of the mice brain, such as hippocampus, hypothalamus and cortex. Time-course experiments indicated that XBP1 splicing was observed from 2h, which was decreased thereafter. On the other hand, we did not observe GRP78 or CHOP induction in homocysteine-treated mice brain. As XBP1 is spliced in response to endoplasmic reticulum (ER) stress and ER stress has been implicated in the pathogenesis of CNS diseases such as Alzheimer's disease and Parkinson's disease, homocysteine-induced XBP1 splicing would be a key mechanism for such diseases.
Hosoi
Toru
T
Department of Pharmacotherapy, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan.
Ogawa
Kazuhiko
K
Ozawa
Koichiro
K
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000235:genetics; D006710:Homocysteine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012326:RNA Splicing / Q000187:drug effects*; D000071701:Regulatory Factor X Transcription Factors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051742:Transcription Factor CHOP / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D000071717:X-Box Binding Protein 1
D017931:DNA Primers; D004268:DNA-Binding Proteins; C497250:Ddit3 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; D006710:Homocysteine; D051742:Transcription Factor CHOP