Intersectin-1s regulates the mitochondrial apoptotic pathway in endothelial cells.

Intersectin-1s regulates the mitochondrial apoptotic pathway in endothelial cells. Research Abstract Details 

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Intersectin-1s regulates the mitochondrial apoptotic pathway in endothelial cells. Abstract Text:

Sanda A Predescu,Dan N Predescu,Ivana Knezevic,Irene K Klein,Asrar B Malik,

Intersectins (ITSNs) are multidomain adaptor proteins implicated in endocytosis, regulation of actin polymerization, and Ras/MAPK signaling. We have previously shown that ITSN-1s is required for caveolae fission and internalization in endothelial cells (ECs). In the present study, using small interfering RNA to knock down ITSN-1s protein expression, we demonstrate a novel role of ITSN-1s as a key antiapoptotic protein. Knockdown of ITSN-1s in ECs activated the mitochondrial pathway of apoptosis as determined by genomic DNA fragmentation, extensive mitochondrial fission, activation of the proapoptotic proteins BAK and BAX, and cytochrome c efflux from mitochondria. ITSN-1 knockdown acts as a proapoptotic signal that causes mitochondrial outer membrane permeabilization, dissipation of the mitochondrial membrane potential, and generation of reactive oxygen species. These effects were secondary to decreased activation of Erk1/2 and its direct activator MEK. Bcl-X(L) overexpression prevented BAX activation and the apoptotic ECs death induced by suppression of ITSN-1s. Our findings demonstrate a novel role of ITSN-1s as a negative regulator of the mitochondrial pathway-dependent apoptosis secondary to activation of the Erk1/2 survival signaling pathway.

Intersectin-1s regulates the mitochondrial apoptotic pathway in endothelial cells. Publishing Authors By Initials

SA Predescu,DN Predescu,I Knezevic,IK Klein,AB Malik,

For similar biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research abstracts see: biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research

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Intersectin-1s regulates the mitochondrial apoptotic pathway in endothelial cells. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 17166-78

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 3

MONTH: 04

YEAR: 2007

Intersectin-1s regulates the mitochondrial apoptotic pathway in endothelial cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Intersectin-1s regulates the mitochondrial apoptotic pathway in endothelial cells. Keywords Mesh Terms:

KEYWORDS: Signal Transduction

MESH TERMS: physiology

Chemical & Substance for Abstract: Intersectin-1s regulates the mitochondrial apoptotic pathway in endothelial cells. Information

Substance Name: Cytochromes c

Registry Number: 9007-43-6

Grant and Affiliation Information for Intersectin-1s regulates the mitochondrial apoptotic pathway in endothelial cells.

AFFILIATION: Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois 60612, USA. sandap@uic.edu

Country: United States

AGENCY: United States NHLBI

GRANT: P01 HL60678

ACRONYM: HL

MEDLINETA: J Biol Chem

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