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Titolo:
Role of ceramide synthase in oxidant injury to renal tubular epithelial cells
Autore:
Ueda, N; Camargo, SMR; Hong, XM; Basnakian, AG; Walker, PD; Shah, SV;
Indirizzi:
Univ Arkansas Med Sci, Div Nephrol, Little Rock, AR 72205 USA Univ Arkansas Med Sci Little Rock AR USA 72205 Little Rock, AR 72205 USA Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA Cent Arkansas Vet Healthcare Syst Little Rock AR USA Little Rock, AR USA
Titolo Testata:
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
fascicolo: 11, volume: 12, anno: 2001,
pagine: 2384 - 2391
SICI:
1046-6673(200111)12:11<2384:ROCSIO>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
DAUNORUBICIN-INDUCED APOPTOSIS; STRESS-INDUCED APOPTOSIS; ACID SPHINGOMYELINASE; DNA-DAMAGE; HUMAN URINE; DEATH; ACCUMULATION; BIOSYNTHESIS; SPHINGOSINE; GENERATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Shah, SV Univ Arkansas Med Sci, Div Nephrol, 4301 W Markham St,Slot 501, Little Rock, AR 72205 USA Univ Arkansas Med Sci 4301 W Markham St,Slot 501 Little Rock AR USA 72205
Citazione:
N. Ueda et al., "Role of ceramide synthase in oxidant injury to renal tubular epithelial cells", J AM S NEPH, 12(11), 2001, pp. 2384-2391

Abstract

Ceramide has been implicated to play an important role in the cell signaling pathway involved in apoptosis. Most studies that have used the apoptoticmodel of cellular injury have suggested that enhanced ceramide generation is the result of the breakdown of sphingomyelin by sphingomyelinases. However, the role of ceramide synthase in enhanced ceramide generation in response to oxidant stress has not been previously examined in any tissue. Hydrogen peroxide (H2O2) (1 MM) resulted in a rapid increase in ceramide generation (as measured by in vitro diacylglycerol kinase assay) in LLC-PK1 cells. The intracellular ceramide level was significantly increased at 5 min afterexposure of cells to H2O2 and thereafter continuously increased up to 60 min. H2O2 also resulted in a rapid increase (within 5 min) in ceramide synthase activity (as measured by incorporation of [C-14] from the labeled palmytoyl-CoA into dihydroceramide) in microsomes. In contrast, the exposure of cells to H2O2 did not result in any significant change in sphingomyelin content or acid or neutral sphingomyelinase activity. An increase in ceramide production induced by H2O2 preceded any evidence of DNA damage and cell death. The specific inhibitor of ceramide synthase, fumonisin B1 (50 muM), wasable to suppress H2O2-induced ceramide generation and provided a marked protection against H2O2-induced DNA strand breaks, DNA fragmentation, and cell death. Taken together, these data provide the first evidence that H2O2 isa regulator of ceramide synthase rather than sphingomyelinases and that ceramide synthase-dependent ceramide generation plays a key role in DNA damage and cell death in oxidant stress to renal tubular epithelial cells.

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Documento generato il 18/01/20 alle ore 07:41:41