상세 정보

underline
Metadata Downloads : dc(xml) or Excel
Cited 0 time in scopus ci

Title 

Age-associated repression of type 1 inositol 1,4,5-triphosphate receptor impairs muscle regeneration

Authors 

Jeong Yi ChoiChae Young HwangBora LeeSeung Min LeeYeong Jae BanKwang-Pyo LeeM KangY S KimS H WooJ Y LimE KimKi Sun Kwon

Publisher 

Impact Journals

Issue Date 

2016

Citation 

Aging, vol. 8, no. 9, pp. 2062-2080

Keywords 

ITPR1Muscle agingMuscle regenerationSarcopeniaU0126

Abstract 

Skeletal muscle mass and power decrease with age, leading to impairment of mobility and metabolism in the elderly. Ca2+ signaling is crucial for myoblast differentiation as well as muscle contraction through activation of transcription factors and Ca2+-dependent kinases and phosphatases. Ca2+ channels, such as dihydropyridine receptor (DHPR), two-pore channel (TPC) and inositol 1,4,5-triphosphate receptor (ITPR), function to maintain Ca2+ homeostasis in myoblasts. Here, we observed a significant decrease in expression of type 1 IP3 receptor (ITPR1), but not types 2 and 3, in aged mice skeletal muscle and isolated myoblasts, compared with those of young mice. ITPR1 knockdown using shRNA-expressing viruses in C2C12 myoblasts and tibialis anterior muscle of mice inhibited myotube formation and muscle regeneration after injury, respectively, a typical phenotype of aged muscle. This aging phenotype was associated with repression of muscle-specific genes and activation of the epidermal growth factor receptor (EGFR)-Ras-extracellular signal-regulated kinase (ERK) pathway. ERK inhibition by U0126 not only induced recovery of myotube formation in old myoblasts but also facilitated muscle regeneration after injury in aged muscle. The conserved decline in ITPR1 expression in aged human skeletal muscle suggests utility as a potential therapeutic target for sarcopenia, which can be treated using ERK inhibition strategies.

ISSN 

1945-4589

Link 

http://dx.doi.org/10.18632/aging.101039

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


Files in This Item: SizeFormat
14357.pdf1351KbAdobe PDF
qrcode

FusionCharts.
DSpace Software Coptright(c) 2010 MIT and Hewleft-Packard  /  KRIBB-REPOSITORY ( Email:jakim@kribb.re.kr)