Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/118735
Title: Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis
Authors: Santana Delgado, María Del Pino 
Peña, Louis A.
Haimovitz-Friedman, Adriana
Martin, Seamus
Green, Douglas
McLoughlin, Maureen
Cordon-Cardo, Carlos
Schuchman, Edward H.
Fuks, Zvi
Kolesnick, Richard
UNESCO Clasification: 32 Ciencias médicas
320713 Oncología
3207 Patología
Keywords: Acid Sphingomyelinase
Apoptosis
Cells
Issue Date: 1996
Journal: Cell 
Abstract: Stress is believed to activate sphingomyelinase to generate ceramide, which serves as a second messenger in initiating the apoptotic response. Conclusive evidence for this paradigm, however, is lacking. In the present study, we used a genetic approach to address this issue directly. We show that lymphoblasts from Niemann-Pick patients, which have an inherited deficiency of acid sphingomyelinase activity, fail to respond to ionizing radiation with ceramide generation and apoptosis. These abnormalities are reversible upon restoration of acid sphingomyelinase activity by retroviral transfer of human acid sphingomyelinase cDNA. Acid sphingomyelinase knockout mice also expressed defects in radiation-induced ceramide generation and apoptosis in vivo. Comparison with p53 knockout mice revealed that acid sphingomyelinase-mediated apoptosis and p53-mediated apoptosis are likely distinct and independent. These genetic models provide definitive evidence for the involvement of acid sphingomyelinase in one form of stress-induced apoptosis.
URI: http://hdl.handle.net/10553/118735
ISSN: 0092-8674
DOI: 10.1016/S0092-8674(00)80091-4
Source: Cell [00925-8674], v. 86 (2), pp. 189-199 (Julio 1996)
Appears in Collections:Artículos
Show full item record

SCOPUSTM   
Citations

748
checked on Dec 15, 2024

WEB OF SCIENCETM
Citations

712
checked on Dec 15, 2024

Page view(s)

55
checked on May 18, 2024

Google ScholarTM

Check

Altmetric


Share



Export metadata



Items in accedaCRIS are protected by copyright, with all rights reserved, unless otherwise indicated.