Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive 

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-51060

Chuang, PY; Dai, Y; Liu, R; He, H; Kretzler, M; Jim, B; Cohen, C D; He, J C (2011). Alteration of forkhead box O (foxo4) acetylation mediates apoptosis of podocytes in diabetes mellitus. PLoS ONE, 6(8):23566.

[img]
Preview
Published Version
PDF
530kB

Abstract

The number of kidney podocytes is reduced in diabetic nephropathy. Advanced glycation end products (AGEs) accumulate
in patients with diabetes and promote the apoptosis of podocyte by activating the forkhead box O4 (Foxo4) transcription
factor to increase the expression of a pro-apoptosis gene, Bcl2l11. Using chromatin immunoprecipitation we demonstrate
that AGE-modified bovine serum albumin (AGE-BSA) enhances Foxo4 binding to a forkhead binding element in the
promoter of Bcl2lll. AGE-BSA also increases the acetylation of Foxo4. Lysine acetylation of Foxo4 is required for Foxo4
binding and transcription of Bcl2l11 in podocytes treated with AGE-BSA. The expression of a protein deacetylase that targets
Foxo4 for deacetylation, sirtuin (Sirt1), is down regulated in cultured podocytes by AGE-BSA treatment and in glomeruli of
diabetic patients. SIRT1 over expression in cultured murine podocytes prevents AGE-induced apoptosis. Glomeruli isolated
from diabetic db/db mice have increased acetylation of Foxo4, suppressed expression of Sirt1, and increased expression of
Bcl2l11 compared to non-diabetic littermates. Together, our data provide evidence that alteration of Foxo4 acetylation and
down regulation of Sirt1 expression in diabetes promote podocyte apoptosis. Strategies to preserve Sirt1 expression or
reduce Foxo4 acetylation could be used to prevent podocyte loss in diabetes.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nephrology
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2011
Deposited On:17 Nov 2011 10:03
Last Modified:03 Jan 2014 15:03
Publisher:Public Library of Science
ISSN:1932-6203
Publisher DOI:10.1371/journal.pone.0023566
PubMed ID:21858169
Citations:Web of Science®. Times Cited: 16
Google Scholar™
Scopus®. Citation Count: 21

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page