Integrin β3 prevents apoptosis of HL-1 cardiomyocytes under conditions of oxidative stress.
Integrin receptors are essential in the regulation of vital cardiac functions, and impaired integrin activity has been associated with cardiac remodeling. Oxidative stress is known to be involved in apoptosis and cardiac remodeling and thus may profoundly influence cardiac function via integrin modulation. The aim of this study was to determine the expression pattern and functional role of integrins in HL-1 cardiomyocytes under conditions of oxidative stress. Gene expression was studied by end-point and real-time PCR; surface protein expression was studied by flow cytometry; integrin knockdown was accomplished by siRNA gene silencing; and apoptosis was studied by annexin V staining and active caspase-3/7 using flow cytometry. Among the various subunits under study (alphav, alpha5, alpha6, and beta1, beta3, beta4, and beta5), the expression of beta3 integrin was significantly increased at both the mRNA and protein levels in cardiomyocytes exposed to 100 micromol/L hydrogen peroxide for 3 h. Gene silencing of beta3 integrin by using siRNA resulted in a 2-fold increase in cardiomyocyte apoptosis upon treatment with hydrogen peroxide. This increase in apoptosis, as measured by annexin V staining, correlated with an increase in active caspase-3/7. Integrin beta3 plays a vital role in preventing cardiomyocyte apoptosis under conditions of oxidative stress.
Shewchuk
Lee J
LJ
Medical Sciences Division, Northern Ontario School of Medicine, Lakehead University, 955 Oliver Road, Thunder Bay, ON P7B 5E1, Canada.
Bryan
Sean
S
Ulanova
Marina
M
Khaper
Neelam
N
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D002460:Cell Line; D006861:Hydrogen Peroxide / Q000494:pharmacology; D039661:Integrin beta3 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D039661:Integrin beta3; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide