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AMPK Activates ULK1 in Skeletal Musc...
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Hagen, Margaret T.
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AMPK Activates ULK1 in Skeletal Muscle Without Increasing Markers of Autophagy.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
AMPK Activates ULK1 in Skeletal Muscle Without Increasing Markers of Autophagy./
作者:
Hagen, Margaret T.
出版者:
Ann Arbor : ProQuest Dissertations & Theses, : 2021,
面頁冊數:
60 p.
附註:
Source: Masters Abstracts International, Volume: 83-02.
Contained By:
Masters Abstracts International83-02.
標題:
Molecular biology. -
電子資源:
https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28495674
ISBN:
9798534667776
AMPK Activates ULK1 in Skeletal Muscle Without Increasing Markers of Autophagy.
Hagen, Margaret T.
AMPK Activates ULK1 in Skeletal Muscle Without Increasing Markers of Autophagy.
- Ann Arbor : ProQuest Dissertations & Theses, 2021 - 60 p.
Source: Masters Abstracts International, Volume: 83-02.
Thesis (M.S.)--Saint Louis University, 2021.
Metabolic disorders and aging diseases impact a large portion of the population. Exercise, and the metabolic stress that it causes in cells, has been shown to have many positive effects in preventing and reducing the impacts of these conditions, in part through the engagement of autophagy, a regulated pathway for degradation of intracellular contents, and modulation of glucose metabolism. We tested the effects of an exercise mimetic, 5-aminoimidazole-4-carboxamide riboside (AICAR), to see what effects it would have on some of the pathways proposed to be responsible for these benefits. We hypothesized that AICAR would cause an increase in levels of autophagy and glucose metabolism through the phosphorylation of Unc51 like kinase (ULK1) and its interaction with downstream proteins. We looked at autophagy related protein 14 (ATG14) for general autophagy, hexokinase (HK) and phosphofructokinase (PFK) activity for the pentose phosphate pathway (PPP) and glycolysis respectively, and both the GTPase ras-related protein-receptor interacting protein 1-dynamin-related protein 1 (RAB9-RIP1-DRP1) pathway and the PTEN-induced kinase 1-Parkin1 (PINK1-Parkin) pathways for mitophagy. We utilized C2C12 myoblasts, a mouse cell line, and satellite cells harvested directly from mouse hindlimbs, and observed the impacts of AICAR and transfected versions of ULK1 with various levels of inhibited function. Western blot analysis of protein phosphorylation levels showed an increase in 5' AMP activated protein kinase (AMPK), and ULK1 levels following AICAR exposure, but no rise in the activation of proteins in the autophagy or mitophagy pathways we looked at downstream of ULK1. Surprisingly, the only significant changes we found were a decrease in ATG14 phosphorylation and PINK1 expression in the cells with AICAR exposure; the other pathways showed no change. These results suggest that activation of AMPK and ULK1 by AICAR is insufficient to induce autophagy or mitophagy, indicating that if exercise does induce autophagy in skeletal muscle, some other aspect in addition to AMPK/ULK1 activation is required for its initiation.
ISBN: 9798534667776Subjects--Topical Terms:
517296
Molecular biology.
Subjects--Index Terms:
5-Aminoimidazole-4-carboxamide ribonucleotide
AMPK Activates ULK1 in Skeletal Muscle Without Increasing Markers of Autophagy.
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Metabolic disorders and aging diseases impact a large portion of the population. Exercise, and the metabolic stress that it causes in cells, has been shown to have many positive effects in preventing and reducing the impacts of these conditions, in part through the engagement of autophagy, a regulated pathway for degradation of intracellular contents, and modulation of glucose metabolism. We tested the effects of an exercise mimetic, 5-aminoimidazole-4-carboxamide riboside (AICAR), to see what effects it would have on some of the pathways proposed to be responsible for these benefits. We hypothesized that AICAR would cause an increase in levels of autophagy and glucose metabolism through the phosphorylation of Unc51 like kinase (ULK1) and its interaction with downstream proteins. We looked at autophagy related protein 14 (ATG14) for general autophagy, hexokinase (HK) and phosphofructokinase (PFK) activity for the pentose phosphate pathway (PPP) and glycolysis respectively, and both the GTPase ras-related protein-receptor interacting protein 1-dynamin-related protein 1 (RAB9-RIP1-DRP1) pathway and the PTEN-induced kinase 1-Parkin1 (PINK1-Parkin) pathways for mitophagy. We utilized C2C12 myoblasts, a mouse cell line, and satellite cells harvested directly from mouse hindlimbs, and observed the impacts of AICAR and transfected versions of ULK1 with various levels of inhibited function. Western blot analysis of protein phosphorylation levels showed an increase in 5' AMP activated protein kinase (AMPK), and ULK1 levels following AICAR exposure, but no rise in the activation of proteins in the autophagy or mitophagy pathways we looked at downstream of ULK1. Surprisingly, the only significant changes we found were a decrease in ATG14 phosphorylation and PINK1 expression in the cells with AICAR exposure; the other pathways showed no change. These results suggest that activation of AMPK and ULK1 by AICAR is insufficient to induce autophagy or mitophagy, indicating that if exercise does induce autophagy in skeletal muscle, some other aspect in addition to AMPK/ULK1 activation is required for its initiation.
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