Oxidative Stress in Keratinocytes: Role in Apoptotic Signaling

Details

• Personal Author:
  Castranova, Vincent ; Fabisiak JP ; Kagan VE ; Kawai K ; Kommineni C ; Shvedova AA ; Tyurin VA ; Tyurina YY
• Description:
  We studied the mechanism(s) through which oxidative stress participates in apoptotic signaling in keratinocytes. We exposed normal human keratinocytes (NHEKs)to cumene hydroperoxide (Cu-OOH, 50-200 microM) for 1 h and found significant and dose-dependent depletion of antioxidant reserves, oxidation of GSH and protein sulfhydryls. We metabolically labeled membrane phospholipids.in NHEKs with oxidation-sensitive cis-parinaric acid (PnA) to detect selective oxidation of specific phospholipid classes. We found that incubation of NHEKs with Cu-OOH resulted in dose-dependent oxidation of PnA-phospholipids: phosphatidylinositol(PI), phosphatidylserine (PS), ,phosphatidylethanolamine (PE) and phosphatidylcholine (PC). Most importantly, PS was significantly more sensitive to Cu-OOH oxidation than other phospholipids. This selective oxidation of PS did not occur in liposomes prepared from PnA-labeled keratinocytes phospholipids. Exposure to Cu-OOH induced extemalization of PS in NHEKs, as evidenced by its chemical labeling with fluorescamine. These oxidative modifications of NHEK phospholipids were not accompanied by gross changes of the phospholipid composition as evidenced by our HPTLC determinations. Together with other assays of apoptosis (caspase-3 activation and DNA laddering), our results suggest that Cu-OOH-induced selective PS oxidation may represent a signaling pathway linked to PS extemalization inkeratinocytes undergoingapoptosis. [Description provided by NIOSH]
• Subjects:
  Antioxidants Environmental Exposure Lipids Occupational Health Safety
• Keywords:
  Antioxidation Exposure Assessment Exposure Levels Phospholipids
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• 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:
  54
• Issue:
  1
• NIOSHTIC Number:
  nn:20020974
• Citation:
  Toxicologist 2000 Mar; 54(1):113
• CAS Registry Number:
  Hydrogen peroxide (CAS RN 7722-84-1)
• Federal Fiscal Year:
  2000
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 39th Annual Meeting, March 19-23, 2000, Philadelphia, Pennsylvania
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c4aa32810e3bf2014b557090b23e163a657303bb0e2190ba5b19b1bcafd68f99e8affc5493e5ad481c3bdaf962072e0daa4baa082db5c4cde92b3dc178e409b4
• Download URL:
  https://stacks.cdc.gov/view/cdc/198580/cdc_198580_DS1.pdf
• File Type:
  [PDF - 173.35 KB ]