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Pre-screened Human Skeletal Muscle Cells
(HSkMC) |
Skeletal muscle cells are major components to form skeletal muscle. They participate not only in force generation for movement, postural support and heat production, but also in metabolic regulations and maintenance of homeostasis. Metabolic dysfunctions of skeletal muscle cells led to various disease developments. The cultured Human Skeletal Muscle Cells (HSkMC) are widely used for a diversity of biomedical studies ranged from cell signaling to drug discovery. HSkMC have been used in the study of genetic muscular diseases such as Malignant Hyperthermia
[1](1). HSkMC also have the potential to act as a cardiac graft, mending damage to the heart (2).Recently, cultured Human Skeletal Muscle Cells have been used in micro gravity experiments to study the effects of low gravity environments on human skeletal muscle (3). Since HSkMC are major target cells of insulin action, they are extensively used for diabetes studies (4).
Our pre-screened Human Skeletal Muscle Cells (HSkMC) are isolated from the skeletal muscle of hamstrings. They retain morphological, biochemical, andmetabolic characteristics of skeletal muscle.
style="mso-spacerun: yes"They are cryopreserved at second passage and can be cultured and propagated for at least 15 population doublings.Our pre-screened HSkMCs can undergo differentiation to exhibit actin and myosin myofilaments. We pre-screened our Human Skeletal Muscle Cells for major cell signaling and metabolic pathways and markers.
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| 1. AMPK Signaling Pathway |
AMP-activated protein kinase (AMPK) is the downstream component of a protein kinase cascade that acts as an intracellular energy sensor maintaining the energy balance within the cell. It is a major cellular regulator of lipid and glucose metabolism. AMPK was activated by exercise in skeletal muscle, reported by Winder and Hardie in 1996, provided the first hint that this signaling pathway might represent the elusive and long-sought system that was responsible for the metabolic changes associated with exercise. It triggered an increasing volume of research that has now largely vindicated this hypothesis (5, 6).
In skeletal muscle, the formation of malonyl CoA is regulated acutely by changes in the activity of acetyl CoA carboxylase (ACC), the enzyme that catalyzes malonyl CoA synthesis. AMPK phosphorylates and inhibits ACC (7). Thus, AMPK can directly regulate the pivotal step of fatty acid synthesis pathway through ACC
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| 2. Insulin Signaling
Pathway |
| Skeletal muscle is one of major target tissue of insulin action. Upon insulin binding, insulin receptor tyrosine kinases are activated and catalyze autophosphorylation of tyrosine residues which provide docking sites for SH2 or PTB domains of downstream signaling components. IRS-1 is one of major immediate substrates of insulin receptor, upon binding to activated insulin receptor through its PTB domain, phosphorylation of IRS-1 occurs. The p85 subunit of PI-3 kinase and Grb2 bind to tyrosine phosphorylated IRS-1 through their SH2 domains respectively and mediate activation of downstream PI-3 kinase-Akt and MAP kinase pathways respectively (8). Akt activation is not only involved in anti-apoptosis, but also in regulation of glucose metabolism. Akt can phosphorylate GSK-3, which led to inhibition of GSK-3 activity and stimulation of glycogen synthesis (9). p70 S6 kinase (p70S6K) was also activated by insulin stimulation and activated p70S6K phosphorylates the 40S ribosomal subunit protein S6 and thus stimulates the translation of mRNAs containing a 5' oligopyrimidine tract(10). On the other hand, insulin stimulation also resulted in activation of various Ser/Thr protein kinases which act on IRS-1. Serine phosphorylation of IRS-1 provided a feedback mechanism for insulin signaling (11). |
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