Identification of apoptotic genes mediating TGF-beta/Smad3-induced cell death in intestinal epithelial cells using a genomic approach.

Identification of apoptotic genes mediating TGF-beta/Smad3-induced cell death in intestinal epithelial cells using a genomic approach. Research Abstract Details 

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Identification of apoptotic genes mediating TGF-beta/Smad3-induced cell death in intestinal epithelial cells using a genomic approach. Abstract Text:

Yanna Cao,Lu Chen,Weili Zhang,Yan Liu,Harry T Papaconstantinou,Craig R Bush,Courtney M Townsend,E Aubrey Thompson,Tien C Ko,

Transforming growth factor (TGF)-beta-dependent apoptosis is important in the elimination of damaged or abnormal cells from normal tissues in vivo. Previously, we have shown that TGF-beta inhibits the growth of rat intestinal epithelial (RIE)-1 cells. However, RIE-1 cells are relatively resistant to TGF-beta-induced apoptosis due to a low endogenous Smad3-to-Akt ratio. Overexpression of Smad3 sensitizes RIE-1 cells (RIE-1/Smad3) to TGF-beta-induced apoptosis by altering the Smad3-to-Akt ratio in favor of apoptosis. In this study, we utilized a genomic approach to identify potential downstream target genes that are regulated by TGF-beta/Smad3. Total RNA samples were analyzed using Affymetrix oligonucleotide microarrays. We found that TGF-beta regulated 518 probe sets corresponding to its target genes. Interestingly, among the known apoptotic genes included in the microarray analyses, only caspase-3 was induced, which was confirmed by real-time RT-PCR. Furthermore, TGF-beta activated caspase-3 through protein cleavage. Upstream of caspase-3, TGF-beta induced mitochondrial depolarization, cytochrome c release, and cleavage of caspase-9, which suggests that the intrinsic apoptotic pathway mediates TGF-beta-induced apoptosis in RIE-1/Smad3 cells.

Identification of apoptotic genes mediating TGF-beta/Smad3-induced cell death in intestinal epithelial cells using a genomic approach. Publishing Authors By Initials

Y Cao,L Chen,W Zhang,Y Liu,HT Papaconstantinou,CR Bush,CM Townsend,EA Thompson,TC Ko,

For similar peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta research

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Identification of apoptotic genes mediating TGF-beta/Smad3-induced cell death in intestinal epithelial cells using a genomic approach. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: American journal of physiology. Gastrointestinal a

VOLUME: 292

Page Numbers: G28-38

Journal Abbreviation: Am. J. Physiol. Gastrointest.

ISSN: 0193-1857

DAY: 10

MONTH: 08

YEAR: 2006

Identification of apoptotic genes mediating TGF-beta/Smad3-induced cell death in intestinal epithelial cells using a genomic approach. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100901227

Identification of apoptotic genes mediating TGF-beta/Smad3-induced cell death in intestinal epithelial cells using a genomic approach. Keywords Mesh Terms:

KEYWORDS: Transforming Growth Factor beta

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Identification of apoptotic genes mediating TGF-beta/Smad3-induced cell death in intestinal epithelial cells using a genomic approach. Information

Substance Name: Caspase 3

Registry Number: EC 3.4.22.-

Grant and Affiliation Information for Identification of apoptotic genes mediating TGF-beta/Smad3-induced cell death in intestinal epithelial cells using a genomic approach.

AFFILIATION: Department of Surgery, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0737, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: R01-DK-060105

ACRONYM: DK

MEDLINETA: Am J Physiol Gastrointest Live

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