Biglycan protects cardiomyocytes against hypoxia/reoxygenation injury: role of nitric oxide.
Biglycan, a proteoglycan component of extracellular matrix, has been suspected to contribute to the development of atherosclerosis, but overexpression of biglycan in transgenic mice has been shown to induce cardioprotective genes including nitric oxide (NO) synthases in the heart. Therefore, here we hypothesized if exogenous administration of biglycan exerts cytoprotection. Primary cardiomyocytes from neonatal rats were subjected to 150 min hypoxia and 2 h reoxygenation. Mortality of cardiomyocytes was dose-dependently attenuated by pretreatment with 1-100 nM biglycan. Biglycan enhanced eNOS mRNA and protein, and significantly increased NO content of cardiomyocytes. The NO synthase inhibitor l-nitro-arginine-methyl-ester significantly attenuated the cytoprotective effect of biglycan. This is the first demonstration that biglycan leads to cytoprotection against hypoxia/reoxygenation injury, and that this phenomenon is partially mediated by an NO-dependent mechanism.
Csont
Tamás
T
Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged, Hungary. tamas.csont@pharmahungary.com
Görbe
Anikó
A
Bereczki
Erika
E
Szunyog
Andrea
A
Aypar
Eda
E
Tóth
Melinda E
ME
Varga
Zoltán V
ZV
Csonka
Csaba
C
Fülöp
Ferenc
F
Sántha
Miklós
M
Ferdinandy
Péter
P
D000818:Animals; D058578:Biglycan; D002470:Cell Survival; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000494:pharmacology*; D000860:Hypoxia; D051379:Mice; D008822:Mice, Transgenic; D032342:Muscle Cells / Q000166:cytology; D032383:Myocytes, Cardiac / Q000166:cytology*; D009569:Nitric Oxide / Q000737:chemistry*; D011509:Proteoglycans / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D015427:Reperfusion Injury / Q000473:pathology; D013997:Time Factors
C546885:Bgn protein, mouse; D058578:Biglycan; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D009569:Nitric Oxide