Background: Hypoxia-induced autophagy and muscle wasting occur in several environmental and pathological conditions. However, the molecular mechanisms underlying the effects of the hypoxia-mimetic agent CoCl on autophagy and muscle atrophy are still unclear.
Methods: C2C12 myotubes were exposed to increasing concentrations of CoCl for 24 hours. Quantitative RT-PCR, Western blotting, and transmission electron microscopy were performed to confirm autophagy occurs. Autophagy proteins were measured to understand the molecule mechanisms. We also inhibited hypoxic autophagy and examined the changes in myogenin expression, myotubes formation, and apoptosis.
Results: Our results showed that CoCl-mimicked hypoxia upregulated the expression of the autophagy-related proteins LC3, HIF-1, BNIP3, p-AMPK, and beclin-1, whereas p62 and p-mTOR were downregulated. In addition, the autophagosome could be observed after CoCl induction. The expression of the autophagy-related E3 ligase parkin and the muscle-specific ubiquitin ligase atrogin-1 was increased by CoCl. Inhibition of autophagy by 3MA increased myogenin expression and promoted myotubes formation and the percentage of cell death was decreased.
Conclusions: Our results confirmed that CoCl-mimicked hypoxia induced autophagy via the HIF-1/BNIP3/beclin-1 and AMPK/mTOR pathways. Our results also revealed an important link between autophagy and muscle atrophy under hypoxia, which may help to develop new therapeutic strategies for muscle diseases.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5494548 | PMC |
| http://dx.doi.org/10.1155/2017/7097580 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
HERC1 E3 Ubiquitin Ligase Is Necessary for Autophagy Processes and for the Maintenance and Homeostasis of Vesicles in Motor Nerve Terminals, but Not for Proteasomal Activity.
Int J Mol Sci
January 2025
Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, 41013 Seville, Spain.
The ubiquitin proteasome system (UPS) is implicated in protein homeostasis. One of the proteins involved in this system is HERC1 E3 ubiquitin ligase, which was associated with several processes including the normal development and neurotransmission at the neuromuscular junction (NMJ), autophagy in projection neurons, myelination of the peripheral nervous system, among others. The tambaleante (tbl) mouse model carries the spontaneous mutation Gly483Glu substitution in the HERC1 E3 protein.
View Article and Find Full Text PDFChanges to the Autophagy-Related Muscle Proteome Following Short-Term Treatment with Ectoine in the Duchenne Muscular Dystrophy Mouse Model mdx.
Int J Mol Sci
January 2025
Neuromuscular Reference Center and Department of Neurology, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium.
The most severe form of muscular dystrophy (MD), known as Duchenne MD (DMD), remains an incurable disease, hence the ongoing efforts to develop supportive therapies. The dysregulation of autophagy, a degradative yet protective mechanism activated when tissues are under severe and prolonged stress, is critically involved in DMD. Treatments that harness autophagic capacities therefore represent a promising therapeutic approach.
View Article and Find Full Text PDFTetrahydrobiopterin in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Friend or Foe?
Biomolecules
January 2025
Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, 2000 E Kenwood Blvd, Milwaukee, WI 53211, USA.
Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS) is a chronic multisystem disease characterized by severe muscle fatigue, pain, dizziness, and brain fog. The two most common symptoms are post-exertional malaise (PEM) and orthostatic intolerance (OI). ME/CFS patients with OI (ME+OI) suffer from dizziness or faintness due to a sudden drop in blood pressure while maintaining an upright posture.
View Article and Find Full Text PDFAbietic Acid Alleviates the Hypoxic Injury of Cardiomyocytes by Adjusting Autophagy and Apoptosis Mediated by miR-30a-5p/GRP78 Axis.
Ann Clin Lab Sci
November 2024
Department of Internal Medicine-Cardiovascular, Hangzhou Xixi Hospital, Hangzhou Sixth People's Hospital, Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
Objective: To explore the influence of abietic acid on the autophagy and apoptosis of cardiomyocytes in rats with acute myocardial infarction (AMI).
Methods: A rat model of AMI was built by ligation of the anterior descending branch of left coronary artery, and a model of hypoxic cardiomyocyte injury was constructed by treating cardiomyocytes with hypoxia. Western blot assay was used to detect the abundance of proteins related to autophagy and apoptosis, MTT assay was used to measure the viability of cardiomyocytes, and the expression level of miR-30a-5p was detected by qRT-PCR.
Transcriptomics reveals the regulatory mechanisms of circRNA in the muscle tissue of cows with ketosis postpartum.
Genomics
January 2025
Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, China. Electronic address:
The transition period from late pregnancy to early lactation in dairy cows involves significant metabolic changes to cope with the challenges related to energy metabolism. Muscle tissue, as the largest energy-metabolizing tissue in dairy cows, plays a crucial role in energy metabolism. Furthermore, circular RNAs (circRNAs) have been shown to play key roles in various biological events.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!