Adrenomedullin 2 protects rat cerebral endothelial cells from oxidative damage in vitro.
Adrenomedullin 2 (AM2, intermedin) is a recently identified new member of the calcitonin gene-related peptide family. We examined whether AM2 can attenuate the increased blood-brain barrier permeability and cerebral endothelial cell (CEC) death induced by oxidative stress in vitro. Hydrogen peroxide (H(2)O(2), 0.5 mM) induced a continuous decrease of the transendothelial electrical resistance (TEER) and resulted in intercellular gap formations in rat CECs co-cultured with astrocytes. AM2 induced cAMP and nitric oxide production, increased TEER, enhanced peripheral localization of F-actin bands, and attenuated the increased permeability induced by H(2)O(2). AM2 treatment preserved mitochondrial membrane potential and improved CEC viability in H(2)O(2) treated cultures. These effects of AM2 were similar to those what were reported for adrenomedullin. These results suggest that AM2 protects CECs against oxidative injury in vitro.
Chen
Lei
L
Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Iseigaoka 1-1, Kitakyushu 807-8555, Japan.
Kis
Bela
B
Hashimoto
Hirofumi
H
Busija
David W
DW
Takei
Yoshio
Y
Yamashita
Hiroshi
H
Ueta
Yoichi
Y
D053607:Adrenomedullin; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D042783:Endothelial Cells / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007211:Indoles; D008928:Mitochondria / Q000187:drug effects; D009479:Neuropeptides / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity*; D051381:Rats; D013997:Time Factors
C499411:Adm2 protein, rat; D007211:Indoles; D009479:Neuropeptides; D018696:Neuroprotective Agents; D016877:Oxidants; D053607:Adrenomedullin; D009569:Nitric Oxide; C007293:DAPI; D006861:Hydrogen Peroxide; D000242:Cyclic AMP