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tert-butyl hydroperoxide/hemoglobin-induced oxidative stress and damage to vascular smooth muscle cells: different effects of nitric oxide and nitrosothiols.

Authors
Shvedova-AA; Tyurina-YY; Gorbunov-NV; Tyurin-VA; Castranova-V; Kommineni-C; Ojimba-J; Gandley-R; McLaughlin-MK; Kagan-VE
Source
Biochem Pharmacol 1999 May; 57(9):989-1001
NIOSHTIC No.
20025400
Abstract
The goal of the present work was to determine whether nitric oxide (NO) released from different donors (NONOates and nitrosothiols) can act as a protective antioxidant against oxidative stress and cytotoxicity induced by extracellular hemoglobin/tert-butyl hydroperoxide (Hb/tert-BuOOH) in vascular smooth muscle cells (VSMCs). No changes in phospholipid composition were found in VSMCs incubated with oxyhemoglobin (oxyHb)/tert-BuOOH. Using our newly developed HPLC-fluorescence technique for measurement of site-specific oxidative stress in membrane phospholipids, we produced VSMCs in which endogenous phospholipids were metabolically labeled with an oxidation-sensitive fluorescent fatty acid, cis-parinaric acid. In these cells, we were able to reliably quantitate oxidative stress in major phospholipid classes-phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, and phosphatidylinositol-induced by tert-BuOOH in the presence of oxyHb or methemoglobin (metHb). The oxidative stress was accompanied by cytotoxic effects of oxyHb/tert-BuOOH and metHb/tert-BuOOH on VSMCs. We further found that an NO donor, (Z)-1-[N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen 1-ium-1,2-diolate (PAPANONO), but not nitrosothiols, protected VSMCs against oxidative stress and cytotoxicity induced by Hb/tert-BuOOH. The protective effect of PAPANONO was most likely due to its ability to form NO-heme Hb (detectable by low temperature EPR spectroscopy and visible spectrophotometry). These findings are important for further understanding the physiological antioxidant role of NO against oxidative stress induced by hemoproteins as well as for pathological hypertensive events induced by extracellular Hb via NO depletion.
Keywords
Hydroperoxides; Stress; Oxidation; Oxidative-processes; Muscle-stress; Muscle-cells; Antioxidants; Antioxidation; Cytotoxicity
Contact
Dr. Anna A. Shvedova, Health Effects Laboratory Division, Pathology and Physiology Research Branch, Mail Stop 2015, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
CODEN
BCPCA6
CAS No.
10102-43-9
Publication Date
19990501
Document Type
Journal Article
Fiscal Year
1999
NTIS Accession No.
NTIS Price
Issue of Publication
9
ISSN
0006-2952
NIOSH Division
HELD
Source Name
Biochemical Pharmacology
State
WV; PA
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