|IL-6 protects against hyperoxia-induced mitochondrial damage via Bcl-2-induced Bak interactions with mitofusins.|
|PMID: 19168699 Owner: NLM Status: MEDLINE|
|Overexpression of IL-6 markedly diminishes hyperoxic lung injury, hyperoxia-induced cell death, and DNA fragmentation, and enhances Bcl-2 expression. We hypothesized that changes in the interactions between Bcl-2 family members play an important role in the IL-6-mediated protective response to oxidative stress. Consistent with this hypothesis, we found that IL-6 induced Bcl-2 expression, both in vivo and in vitro, disrupted interactions between proapoptotic and antiapoptotic factors, and suppressed H(2)O(2)-induced loss of mitochondrial membrane potential in vitro. In addition, IL-6 overexpression in mice protects against hyperoxia-induced lung mitochondrial damage. The overexpression of Bcl-2 in vivo prolonged the survival of mice exposed to hyperoxia and inhibited alveolar capillary protein leakage. In addition, apoptosis-associated DNA fragmentation was substantially reduced in these animals. This IL-6-mediated protection was lost when Bcl-2 was silenced, demonstrating that Bcl-2 is an essential mediator of IL-6 cytoprotection. Finally, Bcl-2 blocked the dissociation of Bak from mitofusin protein (Mfn) 2, and inhibited the interaction between Bak and Mfn1. Taken together, our results suggest that IL-6 induces Bcl-2 expression to perform cytoprotective functions in response to oxygen toxicity, and that this effect is mediated by alterations in the interactions between Bak and Mfns.|
|Aaron B Waxman; Narasaiah Kolliputi|
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|Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-01-23|
|Title: American journal of respiratory cell and molecular biology Volume: 41 ISSN: 1535-4989 ISO Abbreviation: Am. J. Respir. Cell Mol. Biol. Publication Date: 2009 Oct|
|Created Date: 2009-09-16 Completed Date: 2009-10-20 Revised Date: 2013-06-02|
Medline Journal Info:
|Nlm Unique ID: 8917225 Medline TA: Am J Respir Cell Mol Biol Country: United States|
|Languages: eng Pagination: 385-96 Citation Subset: IM|
|Pulmonary Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Bulfinch 148, Boston, MA 02114, USA. firstname.lastname@example.org.|
|APA/MLA Format Download EndNote Download BibTex|
Acute Lung Injury
prevention & control
Apoptosis Regulatory Proteins / metabolism
Cells, Cultured / drug effects, metabolism
Endothelial Cells / drug effects, metabolism
GTP Phosphohydrolases / metabolism*
Hyperoxia / drug therapy*, physiopathology
Interleukin-6 / genetics, pharmacology, physiology*
Lipid Peroxidation / drug effects
Lung / drug effects*, metabolism, pathology
Membrane Proteins / metabolism*
Membrane Transport Proteins / metabolism*
Mice, Inbred C57BL
Mitochondria / drug effects*, metabolism
Mitochondrial Membrane Transport Proteins
Mitochondrial Proteins / metabolism*
Oxidative Stress / drug effects*, physiology
Oxygen / toxicity*
Protein Interaction Mapping
Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors, biosynthesis, genetics, physiology*
RNA, Small Interfering / pharmacology
Recombinant Fusion Proteins / physiology
bcl-2 Homologous Antagonist-Killer Protein / metabolism*
|R01HL074859/HL/NHLBI NIH HHS|
|0/Apoptosis Regulatory Proteins; 0/BAK1 protein, human; 0/Bak1 protein, mouse; 0/IL6 protein, human; 0/Interleukin-6; 0/Membrane Proteins; 0/Membrane Transport Proteins; 0/Mitochondrial Membrane Transport Proteins; 0/Mitochondrial Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/RNA, Small Interfering; 0/Recombinant Fusion Proteins; 0/bcl-2 Homologous Antagonist-Killer Protein; 7782-44-7/Oxygen; EC 3.6.1.-/GTP Phosphohydrolases; EC 3.6.1.-/MFN2 protein, human; EC 3.6.1.-/Mfn1 protein, mouse; EC 3.6.1.-/Mfn2 protein, mouse; EC 3.6.5.-/Mfn1 protein, human|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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