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Never in Mitosis Gene A Related Kinase-6 Attenuates Pressure Overload-Induced Activation of the Protein Kinase B Pathway and Cardiac Hypertrophy

Cardiac hypertrophy appears to be a specialized form of cellular growth that involves the proliferation control and cell cycle regulation. NIMA (never in mitosis, gene A)-related kinase-6 (Nek6) is a cell cycle regulatory gene that could induce centriole duplication, and control cell proliferation a...

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Autores principales: Bian, Zhouyan, Liao, Haihan, Zhang, Yan, Wu, Qingqing, Zhou, Heng, Yang, Zheng, Fu, Jinrong, Wang, Teng, Yan, Ling, Shen, Difei, Li, Hongliang, Tang, Qizhu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999101/
https://www.ncbi.nlm.nih.gov/pubmed/24763737
http://dx.doi.org/10.1371/journal.pone.0096095
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author Bian, Zhouyan
Liao, Haihan
Zhang, Yan
Wu, Qingqing
Zhou, Heng
Yang, Zheng
Fu, Jinrong
Wang, Teng
Yan, Ling
Shen, Difei
Li, Hongliang
Tang, Qizhu
author_facet Bian, Zhouyan
Liao, Haihan
Zhang, Yan
Wu, Qingqing
Zhou, Heng
Yang, Zheng
Fu, Jinrong
Wang, Teng
Yan, Ling
Shen, Difei
Li, Hongliang
Tang, Qizhu
author_sort Bian, Zhouyan
collection PubMed
description Cardiac hypertrophy appears to be a specialized form of cellular growth that involves the proliferation control and cell cycle regulation. NIMA (never in mitosis, gene A)-related kinase-6 (Nek6) is a cell cycle regulatory gene that could induce centriole duplication, and control cell proliferation and survival. However, the exact effect of Nek6 on cardiac hypertrophy has not yet been reported. In the present study, the loss- and gain-of-function experiments were performed in Nek6 gene-deficient (Nek6(−/−)) mice and Nek6 overexpressing H9c2 cells to clarify whether Nek6 which promotes the cell cycle also mediates cardiac hypertrophy. Cardiac hypertrophy was induced by transthoracic aorta constriction (TAC) and then evaluated by echocardiography, pathological and molecular analyses in vivo. We got novel findings that the absence of Nek6 promoted cardiac hypertrophy, fibrosis and cardiac dysfunction, which were accompanied by a significant activation of the protein kinase B (Akt) signaling in an experimental model of TAC. Consistent with this, the overexpression of Nek6 prevented hypertrophy in H9c2 cells induced by angiotonin II and inhibited Akt signaling in vitro. In conclusion, our results demonstrate that the cell cycle regulatory gene Nek6 is also a critical signaling molecule that helps prevent cardiac hypertrophy and inhibits the Akt signaling pathway.
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spelling pubmed-39991012014-04-29 Never in Mitosis Gene A Related Kinase-6 Attenuates Pressure Overload-Induced Activation of the Protein Kinase B Pathway and Cardiac Hypertrophy Bian, Zhouyan Liao, Haihan Zhang, Yan Wu, Qingqing Zhou, Heng Yang, Zheng Fu, Jinrong Wang, Teng Yan, Ling Shen, Difei Li, Hongliang Tang, Qizhu PLoS One Research Article Cardiac hypertrophy appears to be a specialized form of cellular growth that involves the proliferation control and cell cycle regulation. NIMA (never in mitosis, gene A)-related kinase-6 (Nek6) is a cell cycle regulatory gene that could induce centriole duplication, and control cell proliferation and survival. However, the exact effect of Nek6 on cardiac hypertrophy has not yet been reported. In the present study, the loss- and gain-of-function experiments were performed in Nek6 gene-deficient (Nek6(−/−)) mice and Nek6 overexpressing H9c2 cells to clarify whether Nek6 which promotes the cell cycle also mediates cardiac hypertrophy. Cardiac hypertrophy was induced by transthoracic aorta constriction (TAC) and then evaluated by echocardiography, pathological and molecular analyses in vivo. We got novel findings that the absence of Nek6 promoted cardiac hypertrophy, fibrosis and cardiac dysfunction, which were accompanied by a significant activation of the protein kinase B (Akt) signaling in an experimental model of TAC. Consistent with this, the overexpression of Nek6 prevented hypertrophy in H9c2 cells induced by angiotonin II and inhibited Akt signaling in vitro. In conclusion, our results demonstrate that the cell cycle regulatory gene Nek6 is also a critical signaling molecule that helps prevent cardiac hypertrophy and inhibits the Akt signaling pathway. Public Library of Science 2014-04-24 /pmc/articles/PMC3999101/ /pubmed/24763737 http://dx.doi.org/10.1371/journal.pone.0096095 Text en © 2014 Bian et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bian, Zhouyan
Liao, Haihan
Zhang, Yan
Wu, Qingqing
Zhou, Heng
Yang, Zheng
Fu, Jinrong
Wang, Teng
Yan, Ling
Shen, Difei
Li, Hongliang
Tang, Qizhu
Never in Mitosis Gene A Related Kinase-6 Attenuates Pressure Overload-Induced Activation of the Protein Kinase B Pathway and Cardiac Hypertrophy
title Never in Mitosis Gene A Related Kinase-6 Attenuates Pressure Overload-Induced Activation of the Protein Kinase B Pathway and Cardiac Hypertrophy
title_full Never in Mitosis Gene A Related Kinase-6 Attenuates Pressure Overload-Induced Activation of the Protein Kinase B Pathway and Cardiac Hypertrophy
title_fullStr Never in Mitosis Gene A Related Kinase-6 Attenuates Pressure Overload-Induced Activation of the Protein Kinase B Pathway and Cardiac Hypertrophy
title_full_unstemmed Never in Mitosis Gene A Related Kinase-6 Attenuates Pressure Overload-Induced Activation of the Protein Kinase B Pathway and Cardiac Hypertrophy
title_short Never in Mitosis Gene A Related Kinase-6 Attenuates Pressure Overload-Induced Activation of the Protein Kinase B Pathway and Cardiac Hypertrophy
title_sort never in mitosis gene a related kinase-6 attenuates pressure overload-induced activation of the protein kinase b pathway and cardiac hypertrophy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999101/
https://www.ncbi.nlm.nih.gov/pubmed/24763737
http://dx.doi.org/10.1371/journal.pone.0096095
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