SIRT1 regulates oxidant- and cigarette smoke-induced eNOS acetylation in endothelial cells: Role of resveratrol
Arunachalam G, Yao H, Sundar IK, Caito S, Rahman I.
Biochem Biophys Res Commun 2010 Feb 26;393(1):66-72.
Reviewers: David S. Palilla, MD, and Theodore A. Alston, MD, PhD
Massachusetts General Hospital, Harvard Medical School, Boston, MA
Anesthesiologists will encounter cardiovascular patients conversant in this biochemical topic as it has garnered a great deal of attention in the lay press recently. This has included Dr. Oz advising people to boost their sirtuins in a recent article in a magazine published by the American Association of Retired Persons (AARP). This paper provides some background regarding the science behind the recommendations.
Researchers at the University of Rochester have studied cigarette smoke and H2O2 as oxidative stress for endothelial cells cultured from human umbilical vein. The oxidants roughly halved the activity of the protein SIRT1. This so-called sirtuin “plays a critical role in aging, cell cycle regulation, apoptosis and inflammation.” Touted as a youth factor, it is highly expressed in endothelium. One consequence of sirtuin decrease in the endothelial cells was a decrease in the activity of nitric oxide synthesis. Resveratrol, an anti-oxidant component of red wine, boosts sirtuin levels and blocks the sirtuin and NO synthetase decreases caused by the oxidants in vitro.
Chemically, resveratrol is a polyphenol extracted from the peel of red grapes. Of note, it bears obvious structural resemblance to diethylstilbesterol (DES), a nonsteroidal estrogen. Its promotion of youth is endorsed in Hollywood, and, (inevitably) it is known as Reversatrol. Research on the benefits of resveratrol are conflicting, with the literature replete with results in non-human groups that are disproved in subsequent studies. While some cite beneficial effects on lifespan (1) and metabolism (2), others find no significant benefits.
As we are inundated with news of the latest “benefits” of anti-oxidants over the internet and in the press, we should be cautious in recommending their widespread use. A fascinating twist has recently occurred in the story of dietary anti-oxidants and cardiovascular health. A particularly polyphenol-rich fruit juice may have contributed to a tragic outcome as reported in the literature (3). In the report the anti-oxidants appeared to have a definite pharmacological action as the drink was tragically associated with premature closure of the ductus arteriosus in pregnancy (3). While this is one case report, it should be emphasized that as patients may ask us about this (and other) new “therapies” that we be cautious in their widespread recommendations.
1. Valenzano DR, et al. Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol 2006;16: 296.
2. Lagouge M, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 2006;127:1109.
3. Kapadia V, et al. Prenatal closure of the ductus arteriosus and maternal ingestion of anthocyanins. J Perinatol 2010;30:291-294.