Adrenomedullin 2 protects rat cerebral endothelial cells from oxidative damage in vitro

被引:32
作者
Chen, Lei
Kis, Bela
Hashimoto, Hirofumi
Busija, David W.
Takei, Yoshio
Yamashita, Hiroshi
Ueta, Yoichi
机构
[1] Univ Occupat & Environm Hlth, Sch Med, Dept Physiol, Yahatanishi Ku, Kitakyushu, Fukuoka 8078555, Japan
[2] Wake Forest Univ, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA
[3] Univ Tokyo, Ocean Res Inst, Physiol Lab, Tokyo 1648639, Japan
[4] Kyushu Nutr Welfare Univ, Kitakyushu, Fukuoka 8038511, Japan
关键词
adrenomedullin; 2; blood-brain barrier; cerebral endothelial cell; hydrogen peroxide; intermedin; permeability;
D O I
10.1016/j.brainres.2006.02.128
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
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 (H2O2, 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 H2O2. AM2 treatment preserved mitochondrial membrane potential and improved CEC viability in H2O2 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. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:42 / 49
页数:8
相关论文
共 41 条
[1]
Opposite effect of cAMP signaling in endothelial barriers of different origin [J].
Bindewald, K ;
Gündüz, D ;
Härtel, F ;
Peters, SC ;
Rodewald, C ;
Nau, S ;
Schäfer, M ;
Neumann, J ;
Piper, HM ;
Noll, T .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2004, 287 (05) :C1246-C1255
[2]
Extreme hydrops fetalis and cardiovascular abnormalities in mice lacking a functional Adrenomedullin gene [J].
Caron, KM ;
Smithies, O .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (02) :615-619
[3]
Adrenomedullin protects rat cerebral endothelial cells from oxidant damage in vitro [J].
Chen, L ;
Kis, B ;
Busija, DW ;
Yamashita, H ;
Ueta, Y .
REGULATORY PEPTIDES, 2005, 130 (1-2) :27-34
[4]
PENETRATION OF SMALL MOLECULAR-WEIGHT SUBSTANCES THROUGH CULTURED BOVINE BRAIN CAPILLARY ENDOTHELIAL-CELL MONOLAYERS - THE EARLY EFFECTS OF CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE [J].
DELI, MA ;
DEHOUCK, MP ;
ABRAHAM, CS ;
CECCHELLI, R ;
JOO, F .
EXPERIMENTAL PHYSIOLOGY, 1995, 80 (04) :675-678
[5]
Tissue plasminogen activator inhibits P-glycoprotein activity in brain endothelial cells [J].
Deli, MA ;
Abrahám, CS ;
Takahata, H ;
Niwa, M .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2001, 411 (1-2) :R3-R5
[6]
Ehringer WD, 1999, MICROCIRCULATION, V6, P291
[7]
The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton [J].
Fanning, AS ;
Jameson, BJ ;
Jesaitis, LA ;
Anderson, JM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (45) :29745-29753
[8]
Antioxidant therapy in acute central nervous system injury: Current state [J].
Gilgun-Sherki, Y ;
Rosenbaum, Z ;
Melamed, E ;
Offen, D .
PHARMACOLOGICAL REVIEWS, 2002, 54 (02) :271-284
[9]
Cell adhesion: The molecular basis of tissue architecture and morphogenesis [J].
Gumbiner, BM .
CELL, 1996, 84 (03) :345-357
[10]
Phosphorylation and inactivation of BAD by mitochondria-anchored protein kinase A [J].
Harada, H ;
Becknell, B ;
Wilm, M ;
Mann, M ;
Huang, LJS ;
Taylor, SS ;
Scott, JD ;
Korsmeyer, SJ .
MOLECULAR CELL, 1999, 3 (04) :413-422