Potent Induction of Total Cellular and Mitochondrial Antioxidants and Phase 2 Enzymes by Cruciferous Sulforaphane in Rat Aortic Smooth Muscle Cells: Cytoprotection Against Oxidative and Electrophilic Stress

• Published in: Cardiovascular toxicology Vol. 8; no. 3; pp. 115 - 125
• Main Authors: Zhu, Hong, Jia, Zhenquan, Strobl, Jeannine S., Ehrich, Marion, Misra, Hara P., Li, Yunbo
• Format: Journal Article
• Language: English
• Published: New York Humana Press Inc 01-09-2008; Springer Nature B.V
• Subjects: Animals; Antioxidants - metabolism; Antioxidants - pharmacology; Aorta - drug effects; Aorta - enzymology; Biomedical and Life Sciences; Biomedicine; Cardiology; Cell Line; Cell Survival - drug effects; Cytoprotection; Dose-Response Relationship, Drug; Enzyme Induction; Isothiocyanates; Metabolic Detoxication, Phase II - genetics; Mitochondria - drug effects; Mitochondria - enzymology; Muscle, Smooth - drug effects; Muscle, Smooth - metabolism; Muscle, Smooth - pathology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - enzymology; Muscle, Smooth, Vascular - pathology; Muscular system; Oxidants - toxicity; Oxidative Stress - drug effects; Pharmacology/Toxicology; Proteins; Rats; Reactive Oxygen Species - metabolism; RNA, Messenger - biosynthesis; Rodents; Thiocyanates - pharmacology; Time Factors; Antioxidants; Oxidative stress; Electrophilic stress; Aortic smooth muscle cells; Phase 2 enzymes; Sulforaphane
• ISSN: 1530-7905; 1559-0259
• DOI: 10.1007/s12012-008-9020-4

Sulforaphane, a cruciferous isothiocyanate compound, upregulates cytoprotective genes in liver, but its effects on antioxidants and phase 2 defenses in vascular cells are unknown. Here we report that incubation of rat aortic smooth muscle A10 cells with sulforaphane (0.25–5 μM) resulted in concentration-dependent induction of a spectrum of important cellular antioxidants and phase 2 enzymes, including superoxide dismutase (SOD), catalase, the reduced form of glutathione (GSH), glutathione peroxidase, glutathione reductase (GR), glutathione S-transferase (GST), and NAD(P)H:quinone oxidoreductase 1 (NQO1). Sulforaphane also increased levels/activities of SOD, catalase, GSH and GST in isolated mitochondria of aortic smooth muscle cells. Time-dependent sulforaphane-induced increases in the mRNA levels for MnSOD, catalase, the catalytic subunit of γ-glutamylcysteine ligase, GR, GST-A1, GST-P1, and NQO1 were observed. Pretreatment with sulforaphane (0.5, 1, and 5 μM) protected aortic smooth muscle cells from oxidative and electrophilic cytotoxicity induced by xanthine oxidase (XO)/xanthine, H
2
O
2
, SIN-1-derived peroxynitrite, 4-hydroxy-2-nonenal, and acrolein. Furthermore, sulforaphane pretreatment prevented intracellular accumulation of reactive oxygen species (ROS) after exposure of the cells to XO/xanthine, H
2
O
2
, or SIN-1. Taken together, this study demonstrates that in the aortic smooth muscle cells sulforaphane at physiologically relevant concentrations potently induces a series of total cellular as well as mitochondrial antioxidants and phase 2 enzymes, which is accompanied by dramatically increased resistance of these vascular cells to oxidative and electrophilic stress.