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

Lei Chen, Bela Kis, Hirofumi Hashimoto, David W. Busija, Yoshio Takei, Hiroshi Yamashita, Yoichi Ueta

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)42-49
Number of pages8
JournalBrain Research
Volume1086
Issue number1
DOIs
StatePublished - May 1 2006

Bibliographical note

Funding Information:
The authors gratefully thank Nancy Busija for critical reading of the manuscript and to Vicky A. Tobin for her valuable comments. This work was supported by grants from Ajinomoto Co., Ltd. (Japan) for Y.U., Grant-in-Aid for JSPS Fellows (S-05146) for B.K., Grant-in-Aid for the promotion of Occupational Health for the Post Graduate Student of the University of Occupational and Environmental Health for L.C. and by grants from NIH (HL-30260, HL-66074, HL-65380, DK-62372) for D.W.B.

Keywords

  • Adrenomedullin 2
  • Blood-brain barrier
  • Cerebral endothelial cell
  • Hydrogen peroxide
  • Intermedin
  • Permeability

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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