Caspase‐3‐mediated cyclic stretch‐induced myoblast apoptosis via a Fas/FasL‐independent signaling pathway during myogenesis

Abstract

Skeletal muscle cells are exposed to mechanical stretch during embryogenesis. Increased stretch may contribute to cell death, and the molecular regulation by stretch remains incompletely understood. The aim of this study was to investigate the effects of cyclic stretch on cell death and apoptosis in myoblast using a Flexercell Strain Unit. Apoptosis was studied by annexin V binding and PI staining, DNA size analysis, electron microphotograph, and caspase assays. Fas/FasL expression was determined by Western blot. When myoblasts were cultured on a flexible membrane and subjected to cyclic strain stress, apoptosis was observed in a time-dependent manner. We also determined that stretch induced cleavage of caspase-3 and increased caspase-3 activity. Caspase-3 inhibition reduced stretch-induced apoptosis. Protein levels of Fas and FasL remained unchanged. Our findings implicated that stretch-induced cell death is an apoptotic event, and that the activation of caspase cascades is required in stretch-induced cell apoptosis. Furthermore, we had provided evidence that caspase-3 mediated cyclic stretch-induced myoblast apoptosis. Mechanical forces induced activation of caspase-3 via signaling pathways independent of Fas/FasL system.

Piezo1 protein induces the apoptosis of human osteoarthritis-derived chondrocytes by activating caspase-12, the signaling marker of ER stress

“…A previous study exploring the connection between mechanical forces and the apoptosis of myoblast cells, found that the stretching pattern could induce the apoptosis of the cells (25), but to date the mechanism of stretch-induced apoptosis of OA-derived chondrocytes remains unclear. In the present study, we hypothesized that the mechanical force could activate Piezo1, further resulting in the apoptosis of OA-derived chondrocytes during the progression of OA.…”

Simultaneous Study of Mechanical Stretch-Induced Cell Proliferation and Apoptosis on C2C12 Myoblasts

“…The higher the levels of caspase-3, the lower the number of surviving cells [Sandri et al, 2001;Liu et al, 2009;Amna et al, 2013]. We next evaluated apoptosis biochemically by semiquantifying the levels of caspase-3.…”

Cytoprotective effects of phlorofucofuroeckol A isolated from Ecklonia stolonifera against tacrine-treated HepG2 cells

“…Excessive ROS productions induce cell death via activation of Fas (also known as CD95) in human monocytes [12]. Fas activation results in Fas receptor clustering at the plasma membrane and activates caspase-8 which subsequently triggers the proteolytic activations of other caspases, including caspase-3, -6 and -9 [13,14]. The activated caspase-8 cleaves BH3 interacting domain death agonist (Bid) to form truncated Bid (tBid) which induces mitochondrial damage, cell shrinkage, and nuclear condensation [15].…”