Isotope-reinforced polyunsaturated fatty acids protect yeast cells from oxidative stress

详细信息    查看全文

• 作者：Shauna Hill^a ; Kathleen Hirano^a ; Vadim V. Shmanai^b ; Beth N. Marbois^a ; Dragoslav Vidovic^c ; Andrei V. Bekish^d ; Bradley Kay^a ; Vincent Tse^a ; Jonathan Fine^a ; Catherine F. Clarke^a ; ^{cathy@chem.ucla.edu} ; Mikhail S. Shchepinov^e ; ^{misha@retrotope.com}
• 关键词：Isotope effect ; Lipid autoxidation ; Oxidative stress ; Coenzyme Q ; Ubiquinone ; Free radicals
• 刊名：Free Radical Biology and Medicine
• 出版年：2011
• 出版时间：1 January 2011
• 年：2011
• 卷：50
• 期：1
• 页码：130-138
• 全文大小：1200 K

文摘

The facile abstraction of bis-allylic hydrogens from polyunsaturated fatty acids (PUFAs) is the hallmark chemistry responsible for initiation and propagation of autoxidation reactions. The products of these autoxidation reactions can form cross-links to other membrane components and damage proteins and nucleic acids. We report that PUFAs deuterated at bis-allylic sites are much more resistant to autoxidation reactions, because of the isotope effect. This is shown using coenzyme Q-deficient Saccharomyces cerevisiae coq mutants with defects in the biosynthesis of coenzyme Q (Q). Q functions in respiratory energy metabolism and also functions as a lipid-soluble antioxidant. Yeast coq mutants incubated in the presence of the PUFA α-linolenic or linoleic acid exhibit 99 % loss of colony formation after 4 h, demonstrating a profound loss of viability. In contrast, coq mutants treated with monounsaturated oleic acid or with one of the deuterated PUFAs, 11,11-D₂-linoleic or 11,11,14,14-D₄-α-linolenic acid, retain viability similar to wild-type yeast. Deuterated PUFAs also confer protection to wild-type yeast subjected to heat stress. These results indicate that isotope-reinforced PUFAs are stabilized compared to standard PUFAs, and they protect coq mutants and wild-type yeast cells against the toxic effects of lipid autoxidation products. These findings suggest new approaches to controlling ROS-inflicted cellular damage and oxidative stress.