Calcium-regulatory mechanisms

Germain, M., Mathai, J. P., and Shore, G. C., 2002, BH-3-only BIK functions at the endoplasmic reticulum to stimulate cytochrome c release from mitochondria, J. Biol. Chem. 277, pp. 18053—18060 Gincel, D., Zaid, H., and Shoshan-Barmatz, V., 2001, Calcium binding and translocation by the voltage-dependent anion channel a possible regulatory mechanism in mitochondrial function, Biochem. J. 358, pp. 147-155... 

Apart from the phosphorylation theory, other regulatory mechanisms have also been suggested for smooth muscle contraction. A thin-filament protein that has been proposed as a regulatory component is caldesmon [102], Purified caldesmon is a potent inhibitor of actin-tropomyosin interaction with myosin. The mechanisms by which calcium removes this inhibition are controversial. Furthermore, phosphorylation of caldesmon by a caldesmon kinase in vitro has also been implicated in this... 

Overall, these results surest that different regulatory mechanisms may exist in mast cells for the transcription of various cytokines. If these findings apply in vim, then stimuli which favour either activation of PKC or mobilization of intracellular calcium may have distinct effects on the subsequent profile of cytokines released, and hence the type of inflammatory response. Furthermore if heterogeneity exists amongst mast cells in the cytokines they produce, this would provide further evidence that there are subsets of mast cells with specific effector roles. It must be stressed however that the full relevance of these findings to human mast cells is yet to be determined. 

MuUaney, J.M., Yu, M., Ghosh, T.K. and Gill, D.L. (1988). Calcium entry into the inositol 1,4,5-trisphosphate-releasable pool is mediated by a GTP-regulatory mechanism. Proc. Natl. Acad. Sci. USA, 85, 2499-2503. 

The cellular mechanism of lead nephrotoxicity appears to be due to an alteration of calcium homeostasis. Lead (Pb ) competes with calcium (Ca " ") for transport, binding to calmodulin and at other cell calcium regulatory sites. Lead can accumulate in mitochondria using the calcium transporter and disrupt respiration. Interactions of lead with calmodulin can result in a disruption of the calcium messenger system to adversely affect normal cell function. The nuclear inclusion bodies may also alter the cellular function of DNA, although this interaction has not been fully elucidated. 

Apart from activation of protein kinases, increases in the intracellular proton and calcium concentrations or a decrease in the intracellular ATP concentration gradually decrease cell-cell conductance (for review, see27). However, while acidosis in normal hearts reduces dye transfer between cardiomyocytes, the same level of acidosis during ischemia does not,72 pointing to an interaction of several of the above regulatory mechanisms. 

Fig. 2. Ca-regulatory mechanism of troponin and tropomyosin. Abscissa indicates the free calcium ion concentration in arbitrary units. Ordinates indicate (a) the extent of contractile interaction between myosin and actin in the presence of troponin and/or tropomyosin (Ebashi et al, 1969) and (b) the extent of contractile interaction of myosin-actin-tropomyosin in the presence of troponin components (Ohtsuki, 1980). TM, Tropomyosin TN, troponin TN -C, troponin C TN-I, troponin I TN-T, troponin T.

Mitochondrial ADP-ribosylation. Other protein substrates for mono(ADP-ribosyl) transferases continue to be reported, but the best characterized reaction is that of mammalian cell mitochondria. Most mono-ADP-ribosyl-protein conjugates in eukaryotic cells are associated with mitochondria. A specific function, namely, stimulation of calcium release from mitochondria, has been ascribed to ADP-ribosylation activity in this organelle. This could, therefore, be an important cell regulatory mechanism, since numerous calcium-dependent enzymes play an important role in cell functioning. 

ABSTRACT In mammals, nitric oxide (NO) is a reactive free radical involved in diverse physiological functions. NO and its redox-related forms NO+ and NO react with di(oxygen) and its derivatives, with metalloproteins and thiol-containing proteins. NO-mediated nitrosation of proteins represents an important cellular regulatory mechanism. Biosynthesis of NO is catalysed by nitric oxide synthase (NOS). Three isoenzymes representing distinct gene products have been identified the inducible NOS isoform, the constitutive neuronal and endothelial isoforms. Inducible and constitutive NOSs have the same structural features, but their activities differ in their dependence to calcium and the rate of NO produced. The principal NO-mediated functions in mammals are endothelium-dependent relaxation, neurotransmission and immune response. The role of NO in the antitumor immune response comprises both regulatory and effector functions at the intra- or inter-cellular level. The first function includes inhibition of lymphocyte proliferation or participation in different transduction pathways. The second fiinction includes pro- or anti-tumoral effects and NO-mediated cell toxicity or cell resistance to apoptosis. 

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