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The Sirt1/P53 Axis in Diabetic Intervertebral Disc Degeneration Pathogenesis and Therapeutics

Intervertebral disc degeneration (IDD) is one of the major causes of low back pain. Diabetes is a risk factor for IDD and may aggravate IDD in rats; however, the mechanism is poorly understood. Previously, we demonstrated that apoptosis and senescence were increased in diabetic nucleus pulposus (NP)...

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Autores principales: Zhang, Zengjie, Lin, Jialiang, Nisar, Majid, Chen, Tingting, Xu, Tianzhen, Zheng, Gang, Wang, Chenggui, Jin, Haiming, Chen, Jiaoxiang, Gao, Weiyang, Tian, Naifeng, Wang, Xiangyang, Zhang, Xiaolei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754956/
https://www.ncbi.nlm.nih.gov/pubmed/31583043
http://dx.doi.org/10.1155/2019/7959573
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author Zhang, Zengjie
Lin, Jialiang
Nisar, Majid
Chen, Tingting
Xu, Tianzhen
Zheng, Gang
Wang, Chenggui
Jin, Haiming
Chen, Jiaoxiang
Gao, Weiyang
Tian, Naifeng
Wang, Xiangyang
Zhang, Xiaolei
author_facet Zhang, Zengjie
Lin, Jialiang
Nisar, Majid
Chen, Tingting
Xu, Tianzhen
Zheng, Gang
Wang, Chenggui
Jin, Haiming
Chen, Jiaoxiang
Gao, Weiyang
Tian, Naifeng
Wang, Xiangyang
Zhang, Xiaolei
author_sort Zhang, Zengjie
collection PubMed
description Intervertebral disc degeneration (IDD) is one of the major causes of low back pain. Diabetes is a risk factor for IDD and may aggravate IDD in rats; however, the mechanism is poorly understood. Previously, we demonstrated that apoptosis and senescence were increased in diabetic nucleus pulposus (NP) tissues; in the current study, we found that hyperglycaemia may promote the incidence of apoptosis and senescence in NP cells in vitro. Meanwhile, the acetylation of P53, a master transcription factor of apoptosis and senescence, was also found increased in diabetic NP tissues in vivo as well as in hyperglycaemic NP cells in vitro. Sirt1 is an NAD(+)-dependent deacetylase, and we showed that the expression of Sirt1 was decreased in NP tissues, while hyperglycaemia could suppress the expression and activity of Sirt1 in NP cells. Furthermore, we demonstrated that butein may inhibit acetylation of P53 and protect NP cells against hyperglycaemia-induced apoptosis and senescence through Sirt1 activation, as the Sirt1 inhibitor Ex527 may counteract the protective effect of butein in hyperglycaemic NP cells. An in vivo study showed that butein could ameliorate the IDD process in diabetic rats, while Sirt1 was increased and acetyl-p53 was decreased in NP tissues in butein-treated rats. These results indicate that the Sirt1/P53 axis is involved in the pathogenesis of diabetic IDD and may serve as a therapeutic target for diabetic IDD.
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spelling pubmed-67549562019-10-03 The Sirt1/P53 Axis in Diabetic Intervertebral Disc Degeneration Pathogenesis and Therapeutics Zhang, Zengjie Lin, Jialiang Nisar, Majid Chen, Tingting Xu, Tianzhen Zheng, Gang Wang, Chenggui Jin, Haiming Chen, Jiaoxiang Gao, Weiyang Tian, Naifeng Wang, Xiangyang Zhang, Xiaolei Oxid Med Cell Longev Research Article Intervertebral disc degeneration (IDD) is one of the major causes of low back pain. Diabetes is a risk factor for IDD and may aggravate IDD in rats; however, the mechanism is poorly understood. Previously, we demonstrated that apoptosis and senescence were increased in diabetic nucleus pulposus (NP) tissues; in the current study, we found that hyperglycaemia may promote the incidence of apoptosis and senescence in NP cells in vitro. Meanwhile, the acetylation of P53, a master transcription factor of apoptosis and senescence, was also found increased in diabetic NP tissues in vivo as well as in hyperglycaemic NP cells in vitro. Sirt1 is an NAD(+)-dependent deacetylase, and we showed that the expression of Sirt1 was decreased in NP tissues, while hyperglycaemia could suppress the expression and activity of Sirt1 in NP cells. Furthermore, we demonstrated that butein may inhibit acetylation of P53 and protect NP cells against hyperglycaemia-induced apoptosis and senescence through Sirt1 activation, as the Sirt1 inhibitor Ex527 may counteract the protective effect of butein in hyperglycaemic NP cells. An in vivo study showed that butein could ameliorate the IDD process in diabetic rats, while Sirt1 was increased and acetyl-p53 was decreased in NP tissues in butein-treated rats. These results indicate that the Sirt1/P53 axis is involved in the pathogenesis of diabetic IDD and may serve as a therapeutic target for diabetic IDD. Hindawi 2019-09-09 /pmc/articles/PMC6754956/ /pubmed/31583043 http://dx.doi.org/10.1155/2019/7959573 Text en Copyright © 2019 Zengjie Zhang et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhang, Zengjie
Lin, Jialiang
Nisar, Majid
Chen, Tingting
Xu, Tianzhen
Zheng, Gang
Wang, Chenggui
Jin, Haiming
Chen, Jiaoxiang
Gao, Weiyang
Tian, Naifeng
Wang, Xiangyang
Zhang, Xiaolei
The Sirt1/P53 Axis in Diabetic Intervertebral Disc Degeneration Pathogenesis and Therapeutics
title The Sirt1/P53 Axis in Diabetic Intervertebral Disc Degeneration Pathogenesis and Therapeutics
title_full The Sirt1/P53 Axis in Diabetic Intervertebral Disc Degeneration Pathogenesis and Therapeutics
title_fullStr The Sirt1/P53 Axis in Diabetic Intervertebral Disc Degeneration Pathogenesis and Therapeutics
title_full_unstemmed The Sirt1/P53 Axis in Diabetic Intervertebral Disc Degeneration Pathogenesis and Therapeutics
title_short The Sirt1/P53 Axis in Diabetic Intervertebral Disc Degeneration Pathogenesis and Therapeutics
title_sort sirt1/p53 axis in diabetic intervertebral disc degeneration pathogenesis and therapeutics
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754956/
https://www.ncbi.nlm.nih.gov/pubmed/31583043
http://dx.doi.org/10.1155/2019/7959573
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