Title: Abstract 1: Noxa and ceramide: Crosstalk between Bcl-2 family members and ceramide in mediating intrinsic apoptosis in Molt-4 human T-cell leukemia
Abstract: Abstract The sphingolipid breakdown product, ceramide, has been proposed as a coordinator of many cellular processes, one of which is apoptosis. We have previously shown that γ-irradiation induces p53-dependent apoptosis through ceramide accumulation in Molt-4 human T-cell leukemia cell line. Noxa, a BH3-only pro-apoptotic protein and a member in the Bcl-2 family, is activated by p53 and regulates downstream proteins that initiate mitochondrial outer membrane permeabilization (MOMP) and subsequently apoptosis. Here we identify a novel link between Noxa and ceramide in the apoptotic pathway that were previously thought to work independently. Specifically, we knocked down either p53 or Noxa protein expression in γ-irradiated Molt-4 cells and measured ceramide level in response to γ-irradiation. Our results demonstrate that ceramide accumulation requires the expression of both p53 and Noxa whereas inhibition of either p53 or Noxa totally inhibits ceramide accumulation. Furthermore, lipid and protein analysis of mitochondria isolated from Molt-4 cells showed a simultaneous ceramide accumulation and cytochrome c release, suggesting that ceramide's role is intricately related to the execution phase of apoptosis. These findings establish a role for Noxa in regulating ceramide at the mitochondrial level and provide a better understanding of the mechanisms of apoptosis initiated by p53. Citation Format: Hadile Kobeissy, Rouba Hage-Sleiman, Ghassan Dbaibo. Noxa and ceramide: Crosstalk between Bcl-2 family members and ceramide in mediating intrinsic apoptosis in Molt-4 human T-cell leukemia. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1. doi:10.1158/1538-7445.AM2015-1
Publication Year: 2015
Publication Date: 2015-08-01
Language: en
Type: article
Indexed In: ['crossref']
Access and Citation
Cited By Count: 6
AI Researcher Chatbot
Get quick answers to your questions about the article from our AI researcher chatbot