Insight into skeletal muscle mechanotransduction: MAPK activation is quantitatively related to tension

Abstract

The mechanism by which mechanical forces acting through skeletal muscle cells generate intracellular signaling, known as mechanotransduction, and the details of how gene expression and cell size are regulated by this signaling are poorly understood. Mitogen-activated protein kinases (MAPKs) are known to be involved in mechanically induced signaling in various cell types, including skeletal muscle where MAPK activation has been reported in response to contraction and passive stretch. Therefore, the investigation of MAPK activation in response to mechanical stress in skeletal muscle may yield important information about the mechanotransduction process. With the use of a rat plantaris in situ preparation, a wide range of peak tensions was generated through passive stretch and concentric, isometric, and eccentric contractile protocols, and the resulting phosphorylation of c-Jun NH(2)-terminal kinase (JNK), extracellular regulated kinase (ERK), and p38 MAPKs was assessed. Isoforms of JNK and ERK MAPKs were found to be phosphorylated in a tension-dependent manner, such that eccentric > isometric > concentric > passive stretch. Peak tension was found to be a better predictor of MAPK phosphorylation than time-tension integral or rate of tension development. Differences in maximal response amplitude and sensitivity between JNK and ERK MAPKs suggest different roles for these two kinase families in mechanically induced signaling. A strong linear relationship between p54 JNK phosphorylation and peak tension over a 15-fold range in tension (r(2) = 0.89, n = 32) was observed, supporting the fact that contraction-type differences can be explained in terms of tension and demonstrating that MAPK activation is a quantitative reflection of the magnitude of mechanical stress applied to muscle. Thus the measurement of MAPK activation, as an assay of skeletal muscle mechanotransduction, may help elucidate mechanically induced hypertrophy.

Focal adhesion kinase signaling is decreased 56 days following spinal cord injury in rat gastrocnemius

“…31 This relationship must be subject to additional regulatory controls, such as changes in levels of phosphatases, because 56 days following SCI reductions in FAK and cSrc phosphorylation were not associated with altered phosphorylation of ERK1/2, even though it is necessary for growth, maintenance and regulation of muscle myotubes 32 and can be directly related to sarcolemmal tension. 33 Our findings do agree with evidence that ERK1/2 phosphorylation is unchanged following long-term SCI when compared with able-bodied controls. 34 It has been long established that FAK activity can be regulated by FRNK by competing for common substrate-binding sites.…”

Efeitos agudos de vários métodos de treinamento de força no lactato sanguíneo e características de cargas em homens treinados recreacionalmente

“…During the lowering phase of movement, more force could be exerted than during the concentric portion of the lift, thus even after concentric failure, it is possible to continue the exercise with eccentric actions, prolonging training stimuli. Since eccentric actions are known to cause more muscle damage (30)(31) and activate mechanotransduction more than other phases of movement (32) , the FR method should be used to stimulate these adaptative mechanisms, making it suitable to promote gains in strength and hypertrophy as suggested by Ahtiainen et al (17) .…”

Distinct Signaling Pathways Are Activated in Response to Mechanical Stress Applied Axially and Transversely to Skeletal Muscle Fibers

“…Although, recently it has been established that mechanical stress activates the ERK1/2, JNKs, and p38 MAP kinases in skeletal muscle cells (22)(23)(24)(25)(26)(27)(28)(29)(30), the pathways that are involved in the activation of these kinases in response to mechanical stress remain unknown. Furthermore, most of the studies on the activation of MAP kinases were carried out in vitro using hind limb muscle cells, which are loaded in vivo along the direction of the long axis of the muscle fibers.…”