Cell cycle and apoptosis regulatory protein-1: a novel regulator of apoptosis in the colonic mucosa during aging.

Cell cycle and apoptosis regulatory protein-1: a novel regulator of apoptosis in the colonic mucosa during aging. Research Abstract Details 

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Cell cycle and apoptosis regulatory protein-1: a novel regulator of apoptosis in the colonic mucosa during aging. Abstract Text:

Adhip P N Majumdar,Jianhua Du,Yingjie Yu,Hu Xu,Edi Levi,Bhaumik B Patel,Arun K Rishi,Adhip P N Majumdar,Jianhua Du,Yingjie Yu,Hu Xu,Edi Levi,Bhaumik B Patel,Arun K Rishi,Adhip P N Majumdar,Jianhua Du,Yingjie Yu,Hu Xu,Edi Levi,Bhaumik B Patel,Arun K Rishi,

Although the regulatory mechanisms for the age-related rise in proliferation and reduction in apoptosis in the colonic mucosa are yet to be fully delineated, we have demonstrated that these events are associated with increased expression and activation of epithelial growth factor receptor (EGFR)/ErbB-1 and some of its receptor family members (EGFRs), indicating their involvement in these processes. However, the downstream signaling events of EGFR and/or its family members regulating age-related changes in mucosal proliferation and apoptosis remain to be delineated. Cell cycle and apoptosis regulatory protein-1 (CARP-1), a novel growth signaling regulator that we isolated, participates in EGFR-dependent signaling. In the current investigation, we examined the involvement of CARP-1 in colonic mucosal growth-related processes during aging. We report that the age-related reduction in apoptosis in the colonic mucosa is associated with increased expression and tyrosine phosphorylation of not only EGFR but also ErbB-2 and ErbB-3. In contrast, protein and mRNA levels of CARP-1 as well as tyrosine phosphorylation of CARP-1 are decreased. Additionally, we have observed that administration of wortmannin, an inhibitor of phosphatidylinositol 3-kinase activity that accelerates apoptosis in the colonic mucosa of aged rats, causes a marked increase in expression and tyrosine phosphorylation of CARP-1. The age-related decline in CARP-1 expression could partly be attributed to increased methylation of the CARP-1 promoter. Taken together, our data suggest that not only EGFR but also its other members are involved in regulating colonic mucosal growth during aging and that CARP-1 may play a crucial role in transducing EGFRs signals.

Cell cycle and apoptosis regulatory protein-1: a novel regulator of apoptosis in the colonic mucosa during aging. Publishing Authors By Initials

AP Majumdar,J Du,Y Yu,H Xu,E Levi,BB Patel,AK Rishi,AP Majumdar,J Du,Y Yu,H Xu,E Levi,BB Patel,AK Rishi,AP Majumdar,J Du,Y Yu,H Xu,E Levi,BB Patel,AK Rishi,

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Cell cycle and apoptosis regulatory protein-1: a novel regulator of apoptosis in the colonic mucosa during aging. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: American journal of physiology. Gastrointestinal a

VOLUME: 293

Page Numbers: G1215-22

Journal Abbreviation: Am. J. Physiol. Gastrointest.

ISSN: 0193-1857

DAY: 11

MONTH: 10

YEAR: 2007

Cell cycle and apoptosis regulatory protein-1: a novel regulator of apoptosis in the colonic mucosa during aging. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Cell cycle and apoptosis regulatory protein-1: a novel regulator of apoptosis in the colonic mucosa during aging.

AFFILIATION: John D. Dingell VA Medical Center, 4646 John R; Rm: B-4238, Detroit, MI 48201. a.majumdar@wayne.edu).

Country: United States

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MEDLINETA: Am J Physiol Gastrointest Live

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