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The role of heat shock protein 90 in...

Angelo, Giana.

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The role of heat shock protein 90 in the molecular mechanism of vitamin D action.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The role of heat shock protein 90 in the molecular mechanism of vitamin D action./
作者:	Angelo, Giana.
面頁冊數:	150 p.
附註:	Source: Dissertation Abstracts International, Volume: 66-03, Section: B, page: 1293.
Contained By:	Dissertation Abstracts International66-03B.
標題:	Biology, Molecular. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3166795
ISBN:	0542024020

The role of heat shock protein 90 in the molecular mechanism of vitamin D action.
Angelo, Giana.

The role of heat shock protein 90 in the molecular mechanism of vitamin D action. - 150 p.

Source: Dissertation Abstracts International, Volume: 66-03, Section: B, page: 1293.

Thesis (Ph.D.)--Tufts University, 2005.

The active metabolite of vitamin D, 1alpha,25-dihydroxyvitamin D 3 (1,25(OH)2D3), exerts its biological effects through interaction with the vitamin D receptor (VDR), a member of the superfamily of nuclear receptors. Intestinal resistance to the actions of vitamin D contributes to impaired calcium absorption that occurs with aging. It is therefore of interest to identify molecular determinants in the vitamin D signal transduction pathway to help answer why 1,25(OH)2D3 responsiveness decreases with age. Nuclear receptors are among the many client proteins chaperoned by Heat shock protein 90 (Hsp90), and Hsp90 has a clear impact on the function of many nuclear receptors. However, the role of Hsp90 in vitamin D action has not been clearly demonstrated. We hypothesized that Hsp90 level is an important determinant of cellular vitamin D responsiveness and that alterations in endogenous levels of Hsp90 can have a significant impact on the genomic response to 1,25(OH)2D3. We utilized the human adenocarcinoma intestinal cell line, Caco-2, to study the impact of reduced Hsp90 function on vitamin D action. We first inhibited Hsp90 function with the Hsp90-binding drug, geldanamycin (GA). Because GA is associated with several off-target side effects and because Hsp90 consists of two forms, Hsp90alpha and Hsp90beta, we next employed RNA interference (RNAi) to specifically reduce Hsp90beta mRNA and protein expression in Caco-2 cells. Hsp90beta was targeted because it is the constitutive form and has been specifically implicated in nuclear receptor signaling. Both inhibition of Hsp90 function and reduction in Hsp90beta expression resulted in impaired genomic response to 1,25(OH)2D 3. Closer inspection of the mechanism by which Hsp90 impacts the vitamin D response showed that VDR protein levels are not reduced, but that VDR is functionally impaired. We conclude that Hsp90beta is a critical determinant of vitamin D responsiveness in Caco-2 cells.

ISBN: 0542024020Subjects--Topical Terms:

1017719
Biology, Molecular.

The role of heat shock protein 90 in the molecular mechanism of vitamin D action.
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