Involvement of CHOP, an ER-stress apoptotic mediator, in both human sporadic ALS and ALS model mice.
Endoplasmic reticulum (ER) stress-induced neuronal death may play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS). However, whether CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP), an ER-stress apoptotic mediator, is involved in the pathogenesis of ALS is controversial. Here we demonstrate the expression levels and localization of CHOP in spinal cords of both sporadic ALS patients and ALS transgenic mice by immunohistochemistry. In the spinal cords of sporadic ALS patients, CHOP was markedly up-regulated but typically expressed at low levels in those of the control. Likewise, CHOP expression increased at 14 (symptomatic stage) and 18 to 20 weeks (end stage) in ALS transgenic mice spinal cords. Furthermore, localizations of CHOP were merged in motor neurons and glial cells, such as oligodendrocytes, astrocytes, and microglia. These results indicate that the up-regulation of CHOP in motor neurons and glial cells may play pivotal roles in the pathogenesis of ALS.
Ito
Yasushi
Y
Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan.
Yamada
Mitsunori
M
Tanaka
Hirotaka
H
Aida
Kazunari
K
Tsuruma
Kazuhiro
K
Shimazawa
Masamitsu
M
Hozumi
Isao
I
Inuzuka
Takashi
T
Takahashi
Hitoshi
H
Hara
Hideaki
H
D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism; D008875:Middle Aged; D009046:Motor Neurons / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D051742:Transcription Factor CHOP / Q000378:metabolism*
C497249:DDIT3 protein, human; C497250:Ddit3 protein, mouse; C000606290:SOD1 protein, human; D051742:Transcription Factor CHOP; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1