Role of creatine phosphokinase in cellular function and metabolism

1978 ◽  
Vol 56 (5) ◽  
pp. 691-706 ◽  
Author(s):  
V. A. Saks ◽  
L. V. Rosenshtraukh ◽  
V. N. Smirnov ◽  
E. I. Chazov
Keyword(s):  
Energy Transport ◽  
Creatine Phosphokinase ◽  
Surface Membrane ◽  
Creatine Phosphate ◽  
Contractile Force ◽  
Energy Utilization ◽  
Regulatory Factor ◽  
Main Attention ◽  
Intracellular Energy

This paper summarizes the data concerning the role of the creatine phosphokinase system in muscle cells with main attention to the cardiac muscle. Creatine phosphokinase isoenzymes play a key role in the intracellular energy transport from mitochondria to myofibrils and other sites of energy utilization. Due to the existence of the creatine phosphate pathway for energy transport, intracellular creatine phosphate concentration is apparently an important regulatory factor for muscle contraction which influences the contractile force by determining the rate of regeneration of ATP directly available for myosin ATPase, and at the same time controls the activator calcium entry into the myoplasm across the surface membrane of the cells.

Iodoacetate-induced contracture in rat skeletal muscle: possible role of ADP

1991 ◽  
Vol 261 (5) ◽  
pp. C828-C836 ◽  
Author(s):  
R. L. Ruff ◽  
J. Weissman
Keyword(s):  
Direct Action ◽  
Surface Membrane ◽  
Creatine Phosphate ◽  
Iodoacetic Acid ◽  
Contractile Proteins ◽  
Membrane Excitability ◽  
Depolarization Loss ◽  
Ca Sensitivity ◽  
Stimulation Of

The effects of iodoacetic acid (IAA) and ischemic contraction were studied in rat extensor digitorum longus muscles. Ischemic contraction of IAA-treated muscles produced contracture. The onset of contracture was not associated with a change in sarcolemmal electrical properties or reduction in intracellular [ATP]; however, [creatine phosphate] was reduced by 75% and free [ADP] was increased by 665%. Continued stimulation of IAA-treated fibers resulted in depolarization, loss of membrane excitability, further depletion of creatine phosphate, and reduction in [ATP]. The effects seen in IAA-treated muscle did not appear to result from a direct action of IAA on the surface membrane, contractile proteins, or excitation-contraction coupling. The contractures in IAA-treated muscle may have resulted from increased Ca sensitivity of the contractile proteins, increased myoplasmic [Ca], or both. Both effects may have resulted from increased [ADP]. In addition, the reduced acidification during ischemic contraction of IAA-treated fibers compared with control fibers may have further increased the Ca sensitivity of IAA-treated fibers compared with controls.

Energy transport from mitochondria to myofibril by a creatine phosphate shuttle in cardiac cells

1983 ◽  
Vol 245 (5) ◽  
pp. C423-C427 ◽  
Author(s):  
G. McClellan ◽  
A. Weisberg ◽  
S. Winegrad
Keyword(s):  
Small Molecules ◽  
Inorganic Phosphate ◽  
Energy Transport ◽  
Adenine Nucleotide ◽  
Surface Membrane ◽  
Creatine Phosphate ◽  
Cardiac Cells ◽  
Bathing Solution ◽  
Resting Tension ◽  
Creatine Phosphate Shuttle

In hyperpermeable cardiac cells, in which the surface membrane has been made highly permeable to small molecules and ions, resting tension increases when the concentration of ATP falls below 200 microM. Peak resting tension occurs in 10 microM ATP and equals 60% of maximum Ca-activated force in 5 mM ATP. The mitochondria in hyperpermeable cells can maintain an ATP concentration above 200 microM if supplied with O2, substrate, ADP, and inorganic phosphate (Pi). Removal of ATP from the bathing solution does not increase resting tension as long as creatine phosphate is present. However O2, substrate, and Pi cannot lower resting tension in the absence of ATP and creatine phosphate. These results are interpreted as evidence for adenine nucleotide tightly bound to the myofibrils and a creatine phosphate shunt of energy from the mitochondria to the myofibrils.

A model for intracellular energy transport

1982 ◽  
Vol 60 (1) ◽  
pp. 98-102 ◽  
Author(s):  
G. W. Mainwood ◽  
K. Rakusan
Keyword(s):  
Free Energy ◽  
Creatine Kinase ◽  
Oxygen Transfer ◽  
Energy Transport ◽  
Atp Hydrolysis ◽  
Creatine Phosphate ◽  
Free Cell ◽  
Cell Periphery ◽  
Maximum Work ◽  
Intracellular Energy

A model for oxygen transfer to cells from capillaries is considered in which mitochondria are either clustered at the cell periphery around capillaries or homogeneously distributed through the cytosol. The capillary [Formula: see text] required to supply cells utilizing oxygen at the same rate is much less when mitochondria cluster around capillaries. Two alternative mechanisms are considered for distributing energy from peripheral mitochondria to the rest of the cell; i.e., diffusion of ATP or creatine phosphate with enough creatine kinase to ensure equilibrium between the ~P carriers. The latter has clear advantages and would appear to be adequate to supply a fairly large mitochondria-free cell core (e.g., 24-μm diameter) with very little change in ADP levels or in the free energy of ATP hydrolysis at maximum work rates. Thus, a viable alternative to the traditional Krogh model is presented which takes into account the inhomogeneity of the diffusion pathway as a result of mitochondrial clustering.

Correlation Between Changes in the Endogenous Energy Stores and Myocardial Function due to Hypoxia in the Isolated Perfused Rat Heart

1972 ◽  
Vol 50 (4) ◽  
pp. 333-345 ◽  
Author(s):  
N. S. Dhalla ◽  
J. C. Yates ◽  
D. A. Walz ◽  
V. A. McDonald ◽  
R. E. Olson
Keyword(s):  
Heart Rate ◽  
Rat Heart ◽  
Coronary Flow ◽  
Creatine Phosphate ◽  
High Energy ◽  
Contractile Force ◽  
Rate Of Change ◽  
Energy Utilization ◽  
Phosphate Potential ◽  
Hypoxic Heart

On perfusing the isolated rat heart for 7 min with substrate-free hypoxic medium, the contractile force, rate of change of contractile force, time to peak tension, and heart rate declined whereas resting tension increased. The coronary flow and the pH of the perfusate reached maximum and minimum values, respectively, within 2 min of hypoxia whereas the optical density of the perfusate at 260 mμ increased progressively over the 7 min of perfusion with hypoxic medium. The levels of glycogen, creatine phosphate, and ATP declined whereas the concentrations of lactate, ADP, AMP, creatine, and Pi increased during the 1st min of hypoxia at which time the contractile force and heart rate decreased by about 20% of the control values. During the 1st min of hypoxia the diminution in phosphate potential and creatine phosphate/Pi ratio was found to be of greater magnitude than that in the contractile force. Between 2 and 7 min of perfusion with hypoxic medium a marked reduction in contractile force occurred without appreciable changes in the coronary flow, the phosphate potential, the levels of ADP and AMP, and creatine phosphate/Pi ratio. No change in myocardial lipids occurred under the present experimental conditions whereas changes in the electrical activity, time for half relaxation, norepinephrine stores, and mitochondrial structure lagged behind the changes in the high energy phosphate stores due to hypoxia. Although a clear relation between changes in the cardiac function and any one biochemical parameter throughout the period of hypoxia is not apparent from this study, the onset of failure of the hypoxic heart to generate contractility may be considered due to an insufficiency in the process of energy generation. The complete inability of the hypoxic heart to develop contractile force may be due to abnormalities in the processes of energy utilization subserving the mechanisms for the maintenance of ionic gradient and excitation–contraction coupling.

Role of the Cilia Membrane in Control of Microtubule Sliding

1980 ◽  
Vol 38 ◽  
pp. 612-615
Author(s):  
Edna S. Kaneshiro
Keyword(s):  
Control Mechanism ◽  
Beat Frequency ◽  
Surface Membrane ◽  
Ciliary Membrane ◽  
Ciliary Beating ◽  
Ciliary Reversal ◽  
Voltage Dependent ◽  
Reversal Mechanism ◽  
And Function

It is currently believed that ciliary beating results from microtubule sliding which is restricted in regions to cause bending. Cilia beat can be modified to bring about changes in beat frequency, cessation of beat and reversal in beat direction. In ciliated protozoans these modifications which determine swimming behavior have been shown to be related to intracellular (intraciliary) Ca2+ concentrations. The Ca2+ levels are in turn governed by the surface ciliary membrane which exhibits increased Ca2+ conductance (permeability) in response to depolarization. Mutants with altered behaviors have been isolated. Pawn mutants fail to exhibit reversal of the effective stroke of ciliary beat and therefore cannot swim backward. They lack the increased inward Ca2+ current in response to depolarizing stimuli. Both normal and pawn Paramecium made leaky to Ca2+ by Triton extrac¬tion of the surface membrane exhibit backward swimming only in reactivating solutions containing greater than IO-6 M Ca2+ Thus in pawns the ciliary reversal mechanism itself is left operational and only the control mechanism at the membrane is affected. The topographic location of voltage-dependent Ca2+ channels has been identified as a component of the ciliary mem¬brane since the inward Ca2+ conductance response is eliminated by deciliation and the return of the response occurs during cilia regeneration. Since the ciliary membrane has been impli¬cated in the control of Ca2+ levels in the cilium and therefore is the site of at least one kind of control of microtubule sliding, we have focused our attention on understanding the structure and function of the membrane.

Eignung der Kapillarmikroskopie zur Diagnostik und Differenzierung einer ILD

2021 ◽  
pp. 1-3
Author(s):  
Sabine Adler
Keyword(s):  
Computed Tomography ◽  
Creatine Phosphokinase ◽  
Correct Diagnosis ◽  
Diagnostic Assessment ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Nailfold Videocapillaroscopy ◽  
High Resolution Computed Tomography ◽  
Diagnostic Role

Nailfold videocapillaroscopy (NVC) is an easy tool used for the assessment of patients with Raynaud’s phenomenon (RP) as possibly associated with systemic sclerosis (SSc). Recent insights have also highlighted its role in the diagnostic assessment of idiopathic inflammatory myopathies (IIMs). The aim of this study is to describe the diagnostic role of NVC in a series of 361 consecutive patients with interstitial lung disease (ILD). All the patients were assessed by clinical pulmonary and rheumatic examinations, blood exams, high-resolution computed tomography and NVC. NVC was considered positive only in the presence of avascular areas or giant capillaries, but also, the presence of bushy capillaries (BCs) was recorded. NVC was positive in 17.7% of ILD patients and in 78.1% of ILD patients associated with a diagnosis of connective tissue disease (CTD). In 25% of SSc-ILD patients, NVC proved necessary for a correct diagnosis. The presence of BCs and/or NVC positivity in ILD patients with normal levels of creatine phosphokinase is associated with amyopathic IIM, regardless the presence of RP. In conclusion, NVC is useful for the diagnostic assessment of incomplete forms of CTD and in amyopathic IIMs. NVC should be considered in the diagnostic assessment of ILD patients regardless of the presence of RP.

scholarly journals IL6 sensitizes prostate cancer to the antiproliferative effect of IFNα2 through IRF9

2013 ◽  
Vol 20 (5) ◽  
pp. 677-689 ◽  
Author(s):  
Holger H H Erb ◽  
Regina V Langlechner ◽  
Patrizia L Moser ◽  
Florian Handle ◽  
Tineke Casneuf ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cellular Proliferation ◽  
Tissue Expression ◽  
Type I ◽  
Regulatory Factor ◽  
Quantitative Real Time Pcr ◽  
Antiproliferative Effects ◽  
Protein Levels

Development and progression of prostate cancer (PCa) are associated with chronic inflammation. The cytokine interleukin 6 (IL6) can influence progression, differentiation, survival, and angiogenesis of PCa. To identify novel pathways that are triggered by IL6, we performed a gene expression profiling of two PCa cell lines, LNCaP and MDA PCa 2b, treated with 5 ng/ml IL6. Interferon (IFN) regulatory factor 9 (IRF9) was identified as one of the most prevalent IL6-regulated genes in both cell lines. IRF9 is a mediator of type I IFN signaling and acts together with STAT1 and 2 to activate transcription of IFN-responsive genes. The IL6 regulation of IRF9 was confirmed at mRNA and protein levels by quantitative real-time PCR and western blot respectively in both cell lines and could be blocked by the anti-IL6 antibody Siltuximab. Three PCa cell lines, PC3, Du-145, and LNCaP-IL6+, with an autocrine IL6 loop displayed high expression of IRF9. A tissue microarray with 36 PCa tissues showed that IRF9 protein expression is moderately elevated in malignant areas and positively correlates with the tissue expression of IL6. Downregulation and overexpression of IRF9 provided evidence for an IFN-independent role of IRF9 in cellular proliferation of different PCa cell lines. Furthermore, expression of IRF9 was essential to mediate the antiproliferative effects of IFNα2. We concluded that IL6 is an inducer of IRF9 expression in PCa and a sensitizer for the antiproliferative effects of IFNα2.

scholarly journals Intracellular pH modulates the availability of vascular L-type Ca2+ channels.

1994 ◽  
Vol 103 (4) ◽  
pp. 647-663 ◽  
Author(s):  
U Klöckner ◽  
G Isenberg
Keyword(s):  
Intracellular Ph ◽  
Single Channel ◽  
Surface Membrane ◽  
Life Time ◽  
Bicarbonate Buffer ◽  
State Changes ◽  
Channel Currents ◽  
Inside Out ◽  
Ca2 Channels

L-type Ca2+ channel currents were recorded from myocytes isolated from bovine pial and porcine coronary arteries to study the influence of changes in intracellular pH (pHi). Whole cell ICa fell when pHi was made more acidic by substituting HEPES/NaOH with CO2/bicarbonate buffer (pHo 7.4, 36 degrees C), and increased when pHi was made more alkaline by addition of 20 mM NH4Cl. Peak ICa was less pHi sensitive than late ICa (170 ms after depolarization to 0 mV). pHi-effects on single Ca2+ channel currents were studied with 110 mM BaCl2 as the charge carrier (22 degrees C, pHo 7.4). In cell-attached patches pHi was changed by extracellular NH4Cl or through the opened cell. In inside-out patches pHi was controlled through the bath. Independent of the method used the following results were obtained: (a) Single channel conductance (24 pS) and life time of the open state were not influenced by pHi (between pHi 6 and 8.4). (b) Alkaline pHi increased and acidic pHi reduced the channel availability (frequency of nonblank sweeps). (c) Alkaline pHi increased and acidic pHi reduced the frequency of late channel re-openings. The effects are discussed in terms of a deprotonation (protonation) of cytosolic binding sites that favor (prevent) the shift of the channels from a sleepy to an available state. Changes of bath pHo mimicked the pHi effects within 20 s, suggesting that protons can rapidly permeate through the surface membrane of vascular smooth muscle cells. The role of pHi in Ca2+ homeostases and vasotonus is discussed.

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