Nitric Oxide but Not Nitrosothiols Inhibit Tertbutyl Hydroperoxide/Hemoglobin-Induced Oxidative Stress and Cytotoxicity

Details

• Personal Author:
  Castranova, Vincent ; Gandley R ; Gorbunov NV ; Kagan VE ; McLaughlin M ; Ojimba J ; Shvedova AA ; Tyurin VA ; Tyurina YY
• Description:
  Nitric oxide (NO) can interact with a number of biomolecular carriers to form products that retain biological activity. It has been suggested that physiological effects of nitric oxide (e.g.. those associated with endothelium-derived relaxing factors) may be related to NO-adducts, such as a nitrosothiols (Creager MA. Roddy MA. Boles K. Stamler JS. N-acetylcysteine does not influence the activity of endothelium-derived relaxing factor in vivo. Hypertension. 29(2):668-72, 1997). Antioxidant effects of NO are believed to play an important role in its multifunctional physiological activity. The two major antioxidant mechanisms of NO are: (i) direct radical scavenging, and (ii) interaction with hemoproteins that prevent formation of potent oxidants, oxoferryl-associated radicals. In this study, we compared effects of an NO-donor, NOC-15. and two nitrosothiols. NO-GS and NO-Cys, on cytotoxicity and oxidative stress induced by tert-butyl hydroperoxide (tBuOOH)/oxy-hemoglobin (oxyHb) in rat mesenteric smooth muscle cells. We found that tBuOOH/oxyHb induced pronounced peroxidation of major membrane phospholipids-phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine in the cells as measured by a metabolically integrated oxidation-sensitive fluorescent probe, cis-parinaric acid (PnA). PnA-labeled phospholipids in cells were significantly protected against oxidation by NOC-15. Neither NO-Cys nor NO-GS were able to inhibit tBuOOH/ oxyHb-induced oxidation. Similarly, the tBuOOH/oxyHb-induced decrease in cell survival was not affected by either NO-GS or NO-Cys. A complete protection was, however. provided by NOC-15. Our ESR and spectrophoto- metric measurements demonstrated formation of heme nitrosylated Hb in the presence of NOC-15 and lack of heme nitrosylation by either NO-GS or NO-Cys. We conclude that nitrosothiols do not act as antioxidants against hemoglobin-catalyzed oxidative stress induced by peroxides. [Description provided by NIOSH]
• Subjects:
  Antioxidants Cytotoxins Occupational Health Peroxides Safety
• Keywords:
  Antioxidation Cytotoxicity Oxidation Oxidative-processes Physiological-factors Physiological-function Physiological-response
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Ohio ; OSHA Region 10 ; OSHA Region 5 ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DBBS - Division of Biomedical and Behavioral Sciences
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  42
• NIOSHTIC Number:
  nn:20025153
• Citation:
  Toxicologist 1998 Mar; 42(1-S):149
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  1998
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 37th Annual Meeting, March 1-5,1998, Seattle, Washington
• Supplement:
  1-S
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:0ea9c49eebe103cda4bf4d57a05816e97a7037a00cbf5149b21398cb79368e118645ac3a001c095130b6c3c2dbbdb5e1c0a831c7676773ca011de0d6dedb9ece
• Download URL:
  https://stacks.cdc.gov/view/cdc/196639/cdc_196639_DS1.pdf
• File Type:
  [PDF - 148.56 KB ]