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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Bcl-X(L) is the primary mediator of p21 protection against hyperoxia-induced cell death.

Authors: Wu, Yu-Chieh M; O'Reilly, Michael A

Published In Exp Lung Res, (2011 Mar)

Abstract: A tight balance between anti- and proapoptotic members of the Bcl-2 family controls cell survival and death. Exposure to hyperoxia shifts this balance towards a prodeath state that ultimately activates Bak- and Bax-dependent cell death. Mechanisms underlying this shift are undefined; however, the cell cycle inhibitor p21 delays the loss of antiapoptotic Mcl-1 and Bcl-X(L), and protects against hyperoxia. Here, H1299 human lung adenocarcinoma cells are used to investigate how these and other members of the Bcl-2 family cooperate with p21 to protect against hyperoxia. Expression of antiapoptotic Mcl-1 and Bcl-X(L), but not Bcl-2 or A1, declined during hyperoxia, whereas proapoptotic Bak, but not Bax, increased. Conditional overexpression of p21 selectively delayed the loss of Mcl-1 and Bcl-X(L), without affecting expression of the other members. siRNA knockdown of Mcl-1 and Bcl-X(L) sensitized cells to hyperoxia, but only the loss of Bcl-X(L) ablated the protective effects of p21. Conversely, overexpression of Mcl-1 and Bcl-X(L) protected against hyperoxia, but only Bcl-X(L) bound Bak and Bax. Altogether, these data suggest that Bcl-X(L) is the primary mediator by which p21 protects against hyperoxia-induced Bak/Bax-dependent cell death.

PubMed ID: 21128858 Exiting the NIEHS site

MeSH Terms: Adenocarcinoma of Lung; Adenocarcinoma/metabolism; Adenocarcinoma/pathology; Apoptosis/drug effects; Apoptosis/physiology*; Cell Death/drug effects; Cell Death/physiology; Cell Line, Tumor; Cell Survival/drug effects; Cell Survival/physiology; Cyclin-Dependent Kinase Inhibitor p21/genetics; Cyclin-Dependent Kinase Inhibitor p21/metabolism; Cyclin-Dependent Kinase Inhibitor p21/physiology*; Humans; Lung Neoplasms/metabolism; Lung Neoplasms/pathology; Myeloid Cell Leukemia Sequence 1 Protein; Oxygen/administration & dosage*; Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/metabolism; RNA, Small Interfering/genetics; bcl-2 Homologous Antagonist-Killer Protein/metabolism; bcl-2-Associated X Protein/metabolism; bcl-X Protein/genetics; bcl-X Protein/metabolism; bcl-X Protein/physiology*

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