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Muscle-specific inositide phosphatase (MIP/MTMR14) is reduced with age and its loss accelerates skeletal muscle aging process by altering calcium homeostasis

We have recently reported that a novel muscle-specific inositide phosphatase (MIP/MTMR14) plays a critical role in [Ca(2+)](i) homeostasis through dephosphorylation of sn-1-stearoyl-2-arachidonoyl phosphatidylinositol (3,5) bisphosphate (PI(3,5)P2). Loss of function mutations in MIP have been identi...

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Autores principales: Romero-Suarez, Sandra, Shen, Jinhua, Brotto, Leticia, Hall, Todd, Mo, ChengLin, Valdivia, Héctor H., Andresen, Jon, Wacker, Michael, Nosek, Thomas M., Qu, Cheng-Kui, Brotto, Marco
Formato: Texto
Lenguaje:English
Publicado: Impact Journals LLC 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954041/
https://www.ncbi.nlm.nih.gov/pubmed/20817957
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author Romero-Suarez, Sandra
Shen, Jinhua
Brotto, Leticia
Hall, Todd
Mo, ChengLin
Valdivia, Héctor H.
Andresen, Jon
Wacker, Michael
Nosek, Thomas M.
Qu, Cheng-Kui
Brotto, Marco
author_facet Romero-Suarez, Sandra
Shen, Jinhua
Brotto, Leticia
Hall, Todd
Mo, ChengLin
Valdivia, Héctor H.
Andresen, Jon
Wacker, Michael
Nosek, Thomas M.
Qu, Cheng-Kui
Brotto, Marco
author_sort Romero-Suarez, Sandra
collection PubMed
description We have recently reported that a novel muscle-specific inositide phosphatase (MIP/MTMR14) plays a critical role in [Ca(2+)](i) homeostasis through dephosphorylation of sn-1-stearoyl-2-arachidonoyl phosphatidylinositol (3,5) bisphosphate (PI(3,5)P2). Loss of function mutations in MIP have been identified in human centronuclear myopathy. We developed a MIP knockout (MIPKO) animal model and found that MIPKO mice were more susceptible to exercise-induced muscle damage, a trademark of muscle functional changes in older subjects. We used wild-type (Wt) mice and MIPKO mice to elucidate the roles of MIP in muscle function during aging. We found MIP mRNA expression, MIP protein levels, and MIP phosphatase activity significantly decreased in old Wt mice. The mature MIPKO mice displayed phenotypes that closely resembled those seen in old Wt mice: i) decreased walking speed, ii) decreased treadmill activity, iii) decreased contractile force, and iv) decreased power generation, classical features of sarcopenia in rodents and humans. Defective Ca(2+) homeostasis is also present in mature MIPKO and old Wt mice, suggesting a putative role of MIP in the decline of muscle function during aging. Our studies offer a new avenue for the investigation of MIP roles in skeletal muscle function and as a potential therapeutic target to treat aging sarcopenia.
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spelling pubmed-29540412010-10-14 Muscle-specific inositide phosphatase (MIP/MTMR14) is reduced with age and its loss accelerates skeletal muscle aging process by altering calcium homeostasis Romero-Suarez, Sandra Shen, Jinhua Brotto, Leticia Hall, Todd Mo, ChengLin Valdivia, Héctor H. Andresen, Jon Wacker, Michael Nosek, Thomas M. Qu, Cheng-Kui Brotto, Marco Aging (Albany NY) Research Article We have recently reported that a novel muscle-specific inositide phosphatase (MIP/MTMR14) plays a critical role in [Ca(2+)](i) homeostasis through dephosphorylation of sn-1-stearoyl-2-arachidonoyl phosphatidylinositol (3,5) bisphosphate (PI(3,5)P2). Loss of function mutations in MIP have been identified in human centronuclear myopathy. We developed a MIP knockout (MIPKO) animal model and found that MIPKO mice were more susceptible to exercise-induced muscle damage, a trademark of muscle functional changes in older subjects. We used wild-type (Wt) mice and MIPKO mice to elucidate the roles of MIP in muscle function during aging. We found MIP mRNA expression, MIP protein levels, and MIP phosphatase activity significantly decreased in old Wt mice. The mature MIPKO mice displayed phenotypes that closely resembled those seen in old Wt mice: i) decreased walking speed, ii) decreased treadmill activity, iii) decreased contractile force, and iv) decreased power generation, classical features of sarcopenia in rodents and humans. Defective Ca(2+) homeostasis is also present in mature MIPKO and old Wt mice, suggesting a putative role of MIP in the decline of muscle function during aging. Our studies offer a new avenue for the investigation of MIP roles in skeletal muscle function and as a potential therapeutic target to treat aging sarcopenia. Impact Journals LLC 2010-08-25 /pmc/articles/PMC2954041/ /pubmed/20817957 Text en Copyright: ©2010 Romero-Suarez et al. http://creativecommons.org/licenses/by/2.5/ 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 work is properly cited.
spellingShingle Research Article
Romero-Suarez, Sandra
Shen, Jinhua
Brotto, Leticia
Hall, Todd
Mo, ChengLin
Valdivia, Héctor H.
Andresen, Jon
Wacker, Michael
Nosek, Thomas M.
Qu, Cheng-Kui
Brotto, Marco
Muscle-specific inositide phosphatase (MIP/MTMR14) is reduced with age and its loss accelerates skeletal muscle aging process by altering calcium homeostasis
title Muscle-specific inositide phosphatase (MIP/MTMR14) is reduced with age and its loss accelerates skeletal muscle aging process by altering calcium homeostasis
title_full Muscle-specific inositide phosphatase (MIP/MTMR14) is reduced with age and its loss accelerates skeletal muscle aging process by altering calcium homeostasis
title_fullStr Muscle-specific inositide phosphatase (MIP/MTMR14) is reduced with age and its loss accelerates skeletal muscle aging process by altering calcium homeostasis
title_full_unstemmed Muscle-specific inositide phosphatase (MIP/MTMR14) is reduced with age and its loss accelerates skeletal muscle aging process by altering calcium homeostasis
title_short Muscle-specific inositide phosphatase (MIP/MTMR14) is reduced with age and its loss accelerates skeletal muscle aging process by altering calcium homeostasis
title_sort muscle-specific inositide phosphatase (mip/mtmr14) is reduced with age and its loss accelerates skeletal muscle aging process by altering calcium homeostasis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954041/
https://www.ncbi.nlm.nih.gov/pubmed/20817957
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