当前位置： SCI文献检索 > MOLECULAR AND CELLULAR BIOCHEMISTRY期刊下所有文献 > Crosstalk between Noxa, Bcl-2, and ceramide in mediating p53-dependent apoptosis in Molt-4 human T-cell leukemia.

Crosstalk between Noxa, Bcl-2, and ceramide in mediating p53-dependent apoptosis in Molt-4 human T-cell leukemia.

Abstract：

:Ionizing radiation induces apoptosis in human Molt-4 leukemia cells in a p53-dependent manner. The tumor suppressor p53 stimulates various downstream targets that presumably trigger, individually or in concert, de novo ceramide synthesis and intrinsic apoptosis via mitochondrial outer membrane permeabilization (MOMP). Among these targets, BH3-only protein Noxa was found to be promptly activated by p53 prior to ceramide accumulation and apoptosis in response to irradiation. To evaluate the relation between Noxa and ceramide in irradiation-induced apoptosis, Noxa was silenced in Molt-4 cells and apoptosis, p53 expression, and ceramide accumulation were assessed in response to irradiation. In the absence of Noxa, irradiation of Molt-4 cells still induced apoptosis in a p53-dependent manner however ceramide levels decreased significantly although they remained higher than untreated control. Upon irradiation, Noxa was found to translocate to the mitochondria where endogenous ceramide accumulation was observed. In contrast, overexpression of Bcl-2, another mitochondrial protein, in Molt-4 cells abolished the endogenous ceramide accumulation and apoptosis. In irradiation-induced, p53-dependent pathways of apoptosis, the pro-apoptotic Noxa represents one of several, yet to be identified, pathways simultaneously triggered by p53 to produce mitochondrial ceramide accumulation and apoptosis. In contrast, Bcl-2 functions as a broader inhibitor of both ceramide accumulation and apoptosis. Altogether, these results indicate that members of the Bcl-2 family differentially regulate ceramide accumulation and reveal the existence of crosstalk between Bcl-2 family members and ceramide in mediating p53-dependent apoptosis in Molt-4 human T-cell leukemia.

journal_name

Mol Cell Biochem

journal_title

Molecular and cellular biochemistry

authors

Kobeissy H,Hage-Sleiman R,Dakdouk Z,Kozhaya L,Dbaibo G

doi

10.1007/s11010-020-03874-9

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

215-226

issue

1-2

eissn

0300-8177

issn

1573-4919

pii

10.1007/s11010-020-03874-9

journal_volume

475

pub_type

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