Tert-Butyl Hydroperoxide/Hemoglobin-Induced Oxidative Stress and Damage to Vascular Smooth Muscle Cells: Different Effects of Nitric Oxide and Nitrosothiols

Details

• Personal Author:
  Castranova, Vincent ; Gandley R ; Gorbunov NV ; Kagan VE ; Kommineni C ; McLaughlin MK ; Ojimba J ; Shvedova AA ; Tyurin VA ; Tyurina YY
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Antioxidants Cytotoxins Musculoskeletal Diseases Musculoskeletal System Occupational Health Safety
• Keywords:
  Antioxidation Cytotoxicity Hydroperoxides Muscle-cells Muscle-stress Oxidation Oxidative-processes Stress
• ISSN:
  0006-2952
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  57
• Issue:
  9
• NIOSHTIC Number:
  nn:20025400
• Citation:
  Biochem Pharmacol 1999 May; 57(9):989-1001
• Contact Point Address:
  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
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  1999
• Peer Reviewed:
  True
• Source Full Name:
  Biochemical Pharmacology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:856510770483ddec9d60985853085cbb950758b53a30a05777546474cc372624f300214b3dbb02001d7ed6956f888ea8fd0288c6050a0220b7e30d75cc40bcf1
• Download URL:
  https://stacks.cdc.gov/view/cdc/196794/cdc_196794_DS1.pdf
• File Type:
  [PDF - 589.30 KB ]