Comparative Proteomic Analysis of the Mitochondria-associated ER Membrane (MAM) in a Long-term Type 2 Diabetic Rodent Model

Abstract The mitochondria-associated ER membrane (MAM) plays a critical role in cellular energetics and calcium homeostasis; however, how MAM is affected under diabetic condition remains elusive. This study presented a comprehensive proteome profiling of isolated brain MAM from long-term type 2 diab...

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Autores principales:	Jacey Hongjie Ma, Shichen Shen, Joshua J. Wang, Zhanwen He, Amanda Poon, Jun Li, Jun Qu, Sarah X. Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ce9c478c4c0b4f5fa2c4d156f1fa001e
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spelling	oai:doaj.org-article:ce9c478c4c0b4f5fa2c4d156f1fa001e2021-12-02T12:32:00ZComparative Proteomic Analysis of the Mitochondria-associated ER Membrane (MAM) in a Long-term Type 2 Diabetic Rodent Model10.1038/s41598-017-02213-12045-2322https://doaj.org/article/ce9c478c4c0b4f5fa2c4d156f1fa001e2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02213-1https://doaj.org/toc/2045-2322Abstract The mitochondria-associated ER membrane (MAM) plays a critical role in cellular energetics and calcium homeostasis; however, how MAM is affected under diabetic condition remains elusive. This study presented a comprehensive proteome profiling of isolated brain MAM from long-term type 2 diabetic mice vs. non-diabetic controls. MAM protein was extracted efficiently by a surfactant-aided precipitation/on-pellet digestion (SOD) method, and MAM proteome was quantified by an ion-current-based MS1 method combined with nanoLC-MS/MS. A total of 1,313 non-redundant proteins of MAM were identified, among which 144 proteins were found significantly altered by diabetes. In-depth IPA analysis identified multiple disease-relevant signaling pathways associated with the MAM proteome changes in diabetes, most significantly the unfolded protein response (UPR), p53, hypoxia-related transcription factors, and methyl CpG binding protein 2. Using immunofluorescence labeling we confirmed the activation of three UPR branches and increased ERp29 and calreticulin in diabetic retinas. Moreover, we found GRP75, a key MAM tethering protein, was drastically reduced by long-term diabetes. In vitro, acute high glucose treatment reduces ER-mitochondrial contact in retinal endothelial cells. This study provides first insight into the significant alterations in MAM proteome associated with activation of the UPR in diabetes, which may serve as novel benchmarks for the future studies of diabetic complications.Jacey Hongjie MaShichen ShenJoshua J. WangZhanwen HeAmanda PoonJun LiJun QuSarah X. ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-17 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jacey Hongjie Ma Shichen Shen Joshua J. Wang Zhanwen He Amanda Poon Jun Li Jun Qu Sarah X. Zhang Comparative Proteomic Analysis of the Mitochondria-associated ER Membrane (MAM) in a Long-term Type 2 Diabetic Rodent Model
description	Abstract The mitochondria-associated ER membrane (MAM) plays a critical role in cellular energetics and calcium homeostasis; however, how MAM is affected under diabetic condition remains elusive. This study presented a comprehensive proteome profiling of isolated brain MAM from long-term type 2 diabetic mice vs. non-diabetic controls. MAM protein was extracted efficiently by a surfactant-aided precipitation/on-pellet digestion (SOD) method, and MAM proteome was quantified by an ion-current-based MS1 method combined with nanoLC-MS/MS. A total of 1,313 non-redundant proteins of MAM were identified, among which 144 proteins were found significantly altered by diabetes. In-depth IPA analysis identified multiple disease-relevant signaling pathways associated with the MAM proteome changes in diabetes, most significantly the unfolded protein response (UPR), p53, hypoxia-related transcription factors, and methyl CpG binding protein 2. Using immunofluorescence labeling we confirmed the activation of three UPR branches and increased ERp29 and calreticulin in diabetic retinas. Moreover, we found GRP75, a key MAM tethering protein, was drastically reduced by long-term diabetes. In vitro, acute high glucose treatment reduces ER-mitochondrial contact in retinal endothelial cells. This study provides first insight into the significant alterations in MAM proteome associated with activation of the UPR in diabetes, which may serve as novel benchmarks for the future studies of diabetic complications.
format	article
author	Jacey Hongjie Ma Shichen Shen Joshua J. Wang Zhanwen He Amanda Poon Jun Li Jun Qu Sarah X. Zhang
author_facet	Jacey Hongjie Ma Shichen Shen Joshua J. Wang Zhanwen He Amanda Poon Jun Li Jun Qu Sarah X. Zhang
author_sort	Jacey Hongjie Ma
title	Comparative Proteomic Analysis of the Mitochondria-associated ER Membrane (MAM) in a Long-term Type 2 Diabetic Rodent Model
title_short	Comparative Proteomic Analysis of the Mitochondria-associated ER Membrane (MAM) in a Long-term Type 2 Diabetic Rodent Model
title_full	Comparative Proteomic Analysis of the Mitochondria-associated ER Membrane (MAM) in a Long-term Type 2 Diabetic Rodent Model
title_fullStr	Comparative Proteomic Analysis of the Mitochondria-associated ER Membrane (MAM) in a Long-term Type 2 Diabetic Rodent Model
title_full_unstemmed	Comparative Proteomic Analysis of the Mitochondria-associated ER Membrane (MAM) in a Long-term Type 2 Diabetic Rodent Model
title_sort	comparative proteomic analysis of the mitochondria-associated er membrane (mam) in a long-term type 2 diabetic rodent model
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ce9c478c4c0b4f5fa2c4d156f1fa001e
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Comparative Proteomic Analysis of the Mitochondria-associated ER Membrane (MAM) in a Long-term Type 2 Diabetic Rodent Model

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