Induction profile of MANF/ARMET by cerebral ischemia and its implication for neuron protection.
Cerebral ischemia-induced accumulation of unfolded proteins in vulnerable neurons triggers endoplasmic reticulum (ER) stress. Arginine-rich, mutated in early stage tumors (ARMET) is an ER stress-inducible protein and upregulated in the early stage of cerebral ischemia. The purposes of this study were to investigate the characteristics and implications of ARMET expression induced by focal cerebral ischemia. Focal cerebral ischemia in rats was induced by right middle cerebral artery occlusion with a suture; ischemic lesions were assessed by magnetic resonance imaging and histology; neuronal apoptosis was determined by TUNEL staining; the expressions of proteins were measured by immunohistochemistry, immunofluorescent labeling, and Western blotting. ARMET was found to be extensively upregulated in ischemic regions in a time-dependent manner. The expression of ARMET was neuronal in all examined structures in response to the ischemic insult. We also found that ARMET expression is earlier and more sensitive to ischemic stimulation than C/EBP homologous protein (CHOP). ER stress agent tunicamycin induced ARMET and CHOP expressions in the primary cultured neurons. Treatment with recombinant human ARMET promoted neuron proliferation and prevented from neuron apoptosis induced by tunicamycin. These results suggest that cerebral ischemia-induced ARMET expression may be protective to the neurons.
Yu
Yong-Qiang
YQ
Department of Radiology of the First Affiliated Hospital, Anhui Medical University, Hefei, China.
Liu
Lian-Cheng
LC
Wang
Fa-Cai
FC
Liang
Yan
Y
Cha
Da-Qin
DQ
Zhang
Jing-Jing
JJ
Shen
Yu-Jun
YJ
Wang
Hai-Ping
HP
Fang
Shengyun
S
Shen
Yu-Xian
YX
D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004396:Coloring Agents; D004721:Endoplasmic Reticulum / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009414:Nerve Growth Factors; D009474:Neurons / Q000473:pathology*; D011247:Pregnancy; D011506:Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013778:Tetrazolium Salts
D004396:Coloring Agents; C546826:MANF protein, rat; D009414:Nerve Growth Factors; D011506:Proteins; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium