Pathways calcium-dependent

The pattern emerging is therefore complicated in that there is evidence of activation of both calcium-dependent degradative pathways and oxygen radicals in muscle during excessive isometric or concentric activity. The relative role and importance of these two processes is currently unclear. 

A relationship between polyol pathway activity and reduction in endothelium-dependent relaxation in aorta from chronic STZ-diabetic rats has recently been reported (Cameron and Cotter, 1992). In agreement with several previous studies (Oyama et al., 1986 Kamata et al., 1989), endothelial-dependent relaxation was defective in the diabetic rats but the deficit was prevented by prior treatment with an AR inhibitor. The mechanism underlying the defect has been speculated to be due to decreased production of endothelium-derived relaxing factor (EDRF) or nitric oxide, NO (Hattori et al., 1991). It has been speculated that these vascular abnormalities may lead to diminished blood flow in susceptible tissues and contribute to the development of some diabetic complications. NO is synthesized from the amino-acid L-arginine by a calcium-dependent NO synthase, which requires NADPH as a cofactor. Competition for NADPH from the polyol pathway would take place during times of sustained hyperglycaemia and... 

EscargueU-Blanc, 1., Meilhac, O., Pieraggi, M.T., Amal, J.F., Salvayre, R., and Negre-Salvayre, A., 1997, Oxidized LDLs induce massive apoptosis of cultured human endothelial cells through a calcium-dependent pathway. Prevention by aurintricarboxyhc add, Arterioscler. Thromb. Vase. Biol. 17 331-339. 

All muscarinic receptors are members of the seven transmembrane domain, G protein-coupled receptors, and they are structurally and functionally unrelated to nicotinic ACh receptors. Activation of muscarinic receptors by an agonist triggers the release of an intracellular G-protein complex that can specifically activate one or more signal transduction pathways. Fortunately, the cellular responses elicited by odd- versus even-numbered receptor subtypes can be conveniently distinguished. Activation of Ml, M3, and M5 receptors produces an inosine triphosphate (IP3) mediated release of intracellular calcium, the release of diacylglyc-erol (which can activate protein kinase C), and stimulation of adenylyl cyclase. These receptors are primarily responsible for activating calcium-dependent responses, such as secretion by glands and the contraction of smooth muscle. 

Lead will also cause cancers in the kidney and lung in experimental animals. Furthermore, in humans exposed to lead similar tumors have been detected in epidemiological studies. Although the mechanism is not known, it is known that lead interferes with calcium-dependent protein kinases. The activation of PKC-mediated pathways leads to increased DNA synthesis. Thus, lead can cause increased cell replication and, so, hyperplasia. This may underlie the carcinogenicity. Lead may also act as a tumor promoter. 

MBP is present in various mammalian sera and activates the complement system through the classical pathway. It also specifically binds to murine monoclonal IgM and, hence, can be used to purify IgM MAb from mouse ascitic fluids. The binding reaction is calcium-dependent, so that IgM can be specifically eluted with a buffer containing a calcium chelator (e.g., EDTA). 

After activation of the TCR, there is induction of Src family tyrosine kinase (p56lek), which phosphorylates phospholipase Oyl. This is followed by the hydrolysis of phosphatidylinositol 4,5-bisphosphate, resulting in the production of diacyl-glycerol (DAG) and inositol trisphosphate (IP3). Protein kinase C is activated by DAG, which phosphorylates Ras. Ras is a GTPase and its phosphorylation induces Raf and initiation of MAP kinase signaling pathway. IP3 is involved in calcium-dependent activation of IL-2 gene expression via nuclear factor of activated T cells (NFAT). 

Figure 2. A proposed model demonstrating several different prominent calcium-related pathways whose activity may be altered in dystrophic muscle. Increased activity of mechanosensitive channels (MS) and store-activated channels (SOC), which are likely derived from the same gene product (TRPC), and the calcium leak channel, which could represent a proteolyzed TRPC SOC channel. Decreased mechanical coupling between L-type VGCC and ryanodine receptors may increase basal calcium release from calcium stores (not shown). Further, increased IP, and IP, receptor levels may also enhance basal and stimulated calcium-induced calcium release (CICR) from calcium stores. Calcium store depletion can increase translocation of SOCs from intracellular vesicles to the sarcolemma. Finally, the relationship between increased membrane fragility and tearing is less certain, but calcium influx through sarcolemmal tears could lead to calcium-dependent proteolysis and increased activity of calcium leak channels, as well as proteolysis of other targets, and increased release of calcium from intracellular stores through CICR. This model is not meant to be comprehensive, and other calcium-related molecules are discussed in the text...

APP cleavage to occur (Shi et al., 2001), and removal is carried out by furin, a member of the pro-protein convertase enzymes (Bennett et al., 2000). Furin is a calcium dependent protease and so increases in calcium lead to an increase in activity. Treatment of cells with a calcium ionophore (A23187), which depleted intracellular stores of calcium, leads to a reduction in both furin and BACE activity (Bennett et al., 2000) and thus demonstrates one pathway through how intracellular calcium can regulate A 3 production through BACE. 

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