4-PBA prevents diabetic muscle atrophy in rats by modulating ER stress response and ubiquitin-proteasome system
Copyright © 2019 Elsevier B.V. All rights reserved..
PURPOSE: Skeletal muscle is severely affected in diabetes leading to muscle atrophy. Previously we reported the role of ER stress in muscle atrophy due to hyperglycemia. Hence, in the present study, we investigated the effect of a classical ER stress inhibitor, 4-phenylbutyric acid (PBA), on muscle atrophy in diabetic rats.
METHODS: Diabetes was induced in male rats by streptozotocin, and PBA was administered (40 mg/kg/day; intraperitoneal) after two months of diabetes for two more months. Gastrocnemius muscle is collected after four months of experimental period. The cross-sectional area of myocytes was measured on Hematoxylin and Eosin stained muscle sections. Protein levels of ER stress markers, ubiquitin-proteasome system (UPS) components, and apoptosis were analysed by immunoblot. Proteasomal activity and apoptotic cells were measured.
RESULTS: ER stress markers (GRP78, ATF6, ATF4 and CHOP) that are elevated in diabetes are decreased with PBA treatment. PBA also averted diabetes-induced alterations in UPS (higher levels of E1, atrogin-1, UCHL1 and UCHL5, accumulation of ubiquitinated proteins and increased proteasomal activity). Apoptosis mediators-p53, BAX, and cleaved caspase-3 protein levels, and TUNEL positive cells were decreased in PBA treated diabetic rats. PBA notably improved the muscle-cross sectional area.
CONCLUSIONS: Results highlighted the therapeutic potential of PBA in diabetes muscle wastage.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:306 |
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| Enthalten in: |
Chemico-biological interactions - 306(2019) vom: 01. Juni, Seite 70-77 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Reddy, S Sreenivasa [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.06.2019 Date Revised 05.06.2019 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.cbi.2019.04.009 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM296017256 |
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| 100 | 1 | |a Reddy, S Sreenivasa |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a 4-PBA prevents diabetic muscle atrophy in rats by modulating ER stress response and ubiquitin-proteasome system |
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| 500 | |a Date Revised 05.06.2019 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2019 Elsevier B.V. All rights reserved. | ||
| 520 | |a PURPOSE: Skeletal muscle is severely affected in diabetes leading to muscle atrophy. Previously we reported the role of ER stress in muscle atrophy due to hyperglycemia. Hence, in the present study, we investigated the effect of a classical ER stress inhibitor, 4-phenylbutyric acid (PBA), on muscle atrophy in diabetic rats | ||
| 520 | |a METHODS: Diabetes was induced in male rats by streptozotocin, and PBA was administered (40 mg/kg/day; intraperitoneal) after two months of diabetes for two more months. Gastrocnemius muscle is collected after four months of experimental period. The cross-sectional area of myocytes was measured on Hematoxylin and Eosin stained muscle sections. Protein levels of ER stress markers, ubiquitin-proteasome system (UPS) components, and apoptosis were analysed by immunoblot. Proteasomal activity and apoptotic cells were measured | ||
| 520 | |a RESULTS: ER stress markers (GRP78, ATF6, ATF4 and CHOP) that are elevated in diabetes are decreased with PBA treatment. PBA also averted diabetes-induced alterations in UPS (higher levels of E1, atrogin-1, UCHL1 and UCHL5, accumulation of ubiquitinated proteins and increased proteasomal activity). Apoptosis mediators-p53, BAX, and cleaved caspase-3 protein levels, and TUNEL positive cells were decreased in PBA treated diabetic rats. PBA notably improved the muscle-cross sectional area | ||
| 520 | |a CONCLUSIONS: Results highlighted the therapeutic potential of PBA in diabetes muscle wastage | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Diabetes | |
| 650 | 4 | |a ER stress | |
| 650 | 4 | |a Myopathy | |
| 650 | 4 | |a Skeletal muscle | |
| 650 | 4 | |a Ubiquitin-proteasome system | |
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| 650 | 7 | |a Phenylbutyrates |2 NLM | |
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| 700 | 1 | |a Shruthi, Karnam |e verfasserin |4 aut | |
| 700 | 1 | |a Joy, Dorit |e verfasserin |4 aut | |
| 700 | 1 | |a Reddy, G Bhanuprakash |e verfasserin |4 aut | |
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