Cited by 12Muscle Physiology and DisordersGrowth Hormone and Insulin-like Growth FactorsCell death mechanisms and regulation

C2 Skeletal Myoblast Survival, Death, Proliferation and Differentiation: Regulation by Adra1d

Saini, Amarjit, Al-Shanti, Nasser, Stewart, Claire·2010·Cellular Physiology and Biochemistry

Abstract

IGF-I positively impacts on muscle anabolism/regeneration. Using C2 skeletal myoblasts, we previously reported high dose TNF-alpha -induced (10 ng.ml(-1)) cell death is rescued by IGF-I. However, non-myotoxic low dose TNF-alpha (1.25 ng.ml(-1)) elicits a MAPK-mediated apoptotic response when co-incubated with IGF-I (1.5 ng.ml(-1)). Our aim was to investigate these conflicting roles of IGF-I in our model. Insulin array and qRT-PCR identified Adra1d as a potential regulatory gene that was up-regulated in survival and down-regulated under apoptotic conditions. TNF-alpha administration (1.25 or 10 ng.ml(-1)) induced significant decreases ( approximately 50% both incubations) in Adra1d expression relative to DM. IGF-I addition to high dose TNF-alpha (10 ng.ml(-1)) induced myoblast survival and matched a significant (P < 0.05) increase in Adra1d expression. By contrast, IGF-I addition to low dose TNF-alpha (1.25 ng.ml(-1)) induced elevated death resulting in a significant (P < 0.05) decline ( approximately 55%) in Adra1d expression. Pre-administration of PD98059 (20 uM), which rescues death induced by co-incubation of low dose TNF-alpha with IGF-I, Adra1d levels were again comparable to DM control. Since Adra1d was elevated following incubations that induced myoblast survival, we investigated effects of Adra1d siRNA gene silencing under these conditions. Adra1d knockdown resulted in significantly higher levels of cell death under all incubations suggesting Adra1d expression is essential for skeletal muscle cell survival.

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Crossref · 10.1159/000276559

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Authors
Saini, A., Al-Shanti, N., & Stewart, C.
Affiliations
Manchester Metropolitan University (GB)
Venue
Cellular Physiology and Biochemistry
Publisher
S. Karger AG
Published
2010
Volume
25
Issue
2-3
Pages
253-262
ISSN
  • 1015-8987 (ISSN-L)
  • 1421-9778
OpenAlex
W2057019600
Cited by
12
References
40
Citations by year
2022: 3 · 2021: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 1
FWCI
0.13
Type
journal article
Language
en
Open access
closed
Locations
  • Cellular Physiology and Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • e-space (Manchester Metropolitan University) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
skeletal myoblasts, insulin-like growth factor I, TNF-α, apoptosis, myoblast survival, cell proliferation, myogenesis, MAPK signaling, PD98059, siRNA knockdown, muscle regeneration, muscle anabolism
MeSH terms
Animals, Cell Differentiation, Cell Survival, Flavonoids, Insulin-Like Growth Factor I, Tumor Necrosis Factor-alpha, Down-Regulation, Up-Regulation, Apoptosis, Receptors, Adrenergic, alpha-1, Mitogen-Activated Protein Kinase Kinases, Myoblasts, Skeletal, RNA, Small Interfering, Cell Proliferation, Mice, Gene Knockdown Techniques

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