Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Oxidative stress in keratinocytes: role in apoptotic signaling.

Authors
Kagan-VE; Tyurina-YY; Tyurin-VA; Kawai-K; Fabisiak-JP; Kommineni-C; Castranova-V; Shvedova-AA
Source
Toxicologist 2000 Mar; 54(1):113
NIOSHTIC No.
20020974
Abstract
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.
Keywords
Antioxidants; Antioxidation; Phospholipids; Exposure-levels; Exposure-assessment
CAS No.
7722-84-1
Publication Date
20000301
Document Type
Abstract
Fiscal Year
2000
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
1096-6080
NIOSH Division
HELD
Source Name
The Toxicologist. Society of Toxicology 39th Annual Meeting, March 19-23, 2000, Philadelphia, Pennsylvania
State
WV; PA
TOP