Content area
Full Text
Introduction
Loss of skeletal muscle mass, also known as atrophy, may occur in normal aging-related conditions or in chronic pathological conditions, including myopathy, denervation-associated atrophy, cachexia and obesity (1,2). Skeletal muscle atrophy is associated with increased fatigability and metabolic health problems leading to a reduced quality of life, which represents a major public health burden in several countries. Therefore, great efforts have been made to identify therapeutic tools to prevent or retard muscle atrophy. Muscle regeneration is a coordinated process that involves proliferation and differentiation of muscle progenitor cells. Skeletal myoblast differentiation is a multistep process that is associated with cell cycle exit, muscle-specific gene expression, and formation of multinucleated myotubes via myoblast fusion (3). Myogenesis is well-orchestrated by the myogenic basic helix-loop-helix transcription factors, including MyoD, myogenin and myogenic factor 5 (4). Mice lacking MyoD exhibit delayed myogenesis in the limbs and branchial arches (2). The activation of MyoD is a key regulatory step for the induction of myoblast differentiation. Notably, p38 mitogen-activated protein kinases (MAPK) have a fundamental role in muscle differentiation via the activation of chromatin remodeling proteins and myogenic transcription factors, such as MyoD (5). p38 MAPK induces the heterodimerization of MyoD with E proteins, thus resulting in upregulation of muscle-specific genes, including myogenin and myosin heavy chain (MHC) (6,7). Various promyogenic cell surface signaling pathways, such as Cdo-mediated cell adhesion signaling, activate p38 MAPK thereby inducing myoblast differentiation (8).
Corydalis tuber, which is the rhizome of Corydalis turtschaninovii, has been used to treat inflammatory, hemorheological and allergic diseases in Korea and China (9,10). It has previously been reported that several alkaloid compounds can be isolated from Corydalis tuber (10,11). Among these, dehydrocorydaline (DHC) has been demonstrated to suppress the elevated mitochondrial membrane potential in lipopolysaccharide-stimulated macrophages (12), and to inhibit proliferation of breast cancer cells by inducing apoptosis (13). However, the effects of DHC on myoblast differentiation have yet to be described.
In the present study, DHC, which is an isoquinoline alkaloid, was selected in a screening of natural phytochemicals purified from the Corydalis tuber (Papaveraceae) for the activation of MyoD-responsive reporters and induction of MHC in myoblasts. Subsequently, the effects of DHC on myoblast differentiation and the underlying regulatory mechanisms were investigated. Treatment of C2C12 myoblasts with...