High impact information on Ckm

• Regulatory sequences of the M isozyme of the creatine kinase (MCK) gene have been extensively mapped in skeletal muscle, but little is known about the sequences that control cardiac-specific expression [1].
• The promoter and enhancer sequences required for MCK gene expression were assayed by the direct injection of plasmid DNA constructs into adult rat cardiac and skeletal muscle [1].
• The functional role of isozymes binding to sites of energy utilization and production characteristic of the adult myocardium can be evidenced by the functional coupling of M-CK to myofibrillar ATPase and mito-CK to translocase in Triton X-100 and saponin skinned fibers [2].
• During cell maturation, the increasing contribution of oxidative phosphorylation to ATP production, the apparition and binding of mi-CK to mitochondria, the binding of M-CK to myofibrils, turn the cell in a compartmentalized system of energy production [2].
• Thus, the decreased levels of creatine kinase in aging rats is correlated with decreased levels of mRNA encoding the BCK and MCK isoforms but not an isoform shift [3].

Biological context of Ckm

• Thus, beta-adrenergic stimulation induces a switch in CK gene expression from M-CK to B-CK, which is characteristic for the hypertrophied and failing heart [4].
• However, under such conditions myoblasts do not fuse, but withdraw from the cell cycle and accumulate the muscle isoform of creatine kinase (M-CK) [5].
• Creatine kinase (CK) is important for energy transfer and is composed of mitochondrial (mitCK), muscle (MCK), and brain (BCK) subunits, each being the product of separate nuclear genes [6].

Anatomical context of Ckm

• These data suggest that the MCK gene is controlled by different regulatory programs in adult cardiac and skeletal muscle [1].
• The steady-state levels of the left ventricle mRNAs for alpha myosin heavy chain (alpha-MHC), beta myosin heavy chain (beta-MHC), M creatine kinase (MCK), and B creatine kinase (BCK) were then determined using Northern and slot blot hybridizations [7].

Analytical, diagnostic and therapeutic context of Ckm

• After beta-adrenergic stimulation (iso 3 h) but not after control perfusion (control 3 h) a roughly threefold increase in B-CK mRNA levels and a decrease in M-CK mRNA levels by 18% was found [4].
• Left ventricular tissue was analyzed for total CK-activity, CK-isoenzyme distribution and, by use of quantitative RT-PCR, for B-CK, M-CK, mito-CK and GAPDH- (as internal standard) mRNA [4].

References