Cardiac transcription factor Nkx2.5 is downregulated under excessive O-GlcNAcylation condition.
Post-translational modification of proteins with O-linked N-acetylglucosamine (O-GlcNAc) is linked the development of diabetic cardiomyopathy. We investigated whether Nkx2.5 protein, a cardiac transcription factor, is regulated by O-GlcNAc. Recombinant Nkx2.5 (myc-Nkx2.5) proteins were reduced by tr...
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2012-01-01
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doaj-da5f93d2b6074d438caa331b9e6405292020-11-25T00:47:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e3805310.1371/journal.pone.0038053Cardiac transcription factor Nkx2.5 is downregulated under excessive O-GlcNAcylation condition.Hoe Suk KimJi Soo WooHyun Jung JooWoo Kyung MoonPost-translational modification of proteins with O-linked N-acetylglucosamine (O-GlcNAc) is linked the development of diabetic cardiomyopathy. We investigated whether Nkx2.5 protein, a cardiac transcription factor, is regulated by O-GlcNAc. Recombinant Nkx2.5 (myc-Nkx2.5) proteins were reduced by treatment with the O-GlcNAcase inhibitors STZ and O-(2-acetamido-2-deoxy-D-glucopyroanosylidene)-amino-N-phenylcarbamate; PUGNAC) as well as the overexpression of recombinant O-GlcNAc transferase (OGT-flag). Co-immunoprecipitation analysis revealed that myc-Nkx2.5 and OGT-flag proteins interacted and myc-Nkx2.5 proteins were modified by O-GlcNAc. In addition, Nkx2.5 proteins were reduced in the heart tissue of streptozotocin (STZ)-induced diabetic mice and O-GlcNAc modification of Nkx2.5 protein increased in diabetic heart tissue compared with non-diabetic heart. Thus, excessive O-GlcNAcylation causes downregulation of Nkx2.5, which may be an underlying contributing factor for the development of diabetic cardiomyopathy.http://europepmc.org/articles/PMC3376112?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hoe Suk Kim Ji Soo Woo Hyun Jung Joo Woo Kyung Moon |
spellingShingle |
Hoe Suk Kim Ji Soo Woo Hyun Jung Joo Woo Kyung Moon Cardiac transcription factor Nkx2.5 is downregulated under excessive O-GlcNAcylation condition. PLoS ONE |
author_facet |
Hoe Suk Kim Ji Soo Woo Hyun Jung Joo Woo Kyung Moon |
author_sort |
Hoe Suk Kim |
title |
Cardiac transcription factor Nkx2.5 is downregulated under excessive O-GlcNAcylation condition. |
title_short |
Cardiac transcription factor Nkx2.5 is downregulated under excessive O-GlcNAcylation condition. |
title_full |
Cardiac transcription factor Nkx2.5 is downregulated under excessive O-GlcNAcylation condition. |
title_fullStr |
Cardiac transcription factor Nkx2.5 is downregulated under excessive O-GlcNAcylation condition. |
title_full_unstemmed |
Cardiac transcription factor Nkx2.5 is downregulated under excessive O-GlcNAcylation condition. |
title_sort |
cardiac transcription factor nkx2.5 is downregulated under excessive o-glcnacylation condition. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
Post-translational modification of proteins with O-linked N-acetylglucosamine (O-GlcNAc) is linked the development of diabetic cardiomyopathy. We investigated whether Nkx2.5 protein, a cardiac transcription factor, is regulated by O-GlcNAc. Recombinant Nkx2.5 (myc-Nkx2.5) proteins were reduced by treatment with the O-GlcNAcase inhibitors STZ and O-(2-acetamido-2-deoxy-D-glucopyroanosylidene)-amino-N-phenylcarbamate; PUGNAC) as well as the overexpression of recombinant O-GlcNAc transferase (OGT-flag). Co-immunoprecipitation analysis revealed that myc-Nkx2.5 and OGT-flag proteins interacted and myc-Nkx2.5 proteins were modified by O-GlcNAc. In addition, Nkx2.5 proteins were reduced in the heart tissue of streptozotocin (STZ)-induced diabetic mice and O-GlcNAc modification of Nkx2.5 protein increased in diabetic heart tissue compared with non-diabetic heart. Thus, excessive O-GlcNAcylation causes downregulation of Nkx2.5, which may be an underlying contributing factor for the development of diabetic cardiomyopathy. |
url |
http://europepmc.org/articles/PMC3376112?pdf=render |
work_keys_str_mv |
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