Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.6.1.2 (guanylate cyclase)
8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The flagellar creatine kinase (TCK) of Strongylocentrotus purpuratus sperm is both a principal component of sperm tail membrane preparations and a cytosolic enzyme. An improved purification scheme identified three pools of TCK, termed TCK I, TCK II, and TCK III. TCK I and II were essentially homogeneous protein preparations, while TCK III was heavily contaminated with other flagellar proteins, predominantly guanylate cyclase, and alpha- and beta-tubulin. The three TCK species are roughly present in a 1:10:1 ratio as assessed by activity measurements. TCK I and II are similar proteins as shown by two-dimensional gel electrophoresis, partial proteolytic fragmentation, and cellulose polyacetate electrophoresis and have the same pH-dependent specific activity. However, they are functionally distinct with respect to their capacity to associate with lipids. TCK II associated readily with phospholipid liposomes and detergent micelles, while TCK I did not. Association of TCK II was as a protein monomer with an apparent Kd of approximately 1-2 mM at a 10(4):1 lipid or detergent to protein ratio. Whereas the Kd estimates were pH independent, the rate of association increased 2-3-fold between pH 6.5 and 8. The data are consistent with membrane-association of TCK II being a two-step process, involving a pH-dependent, intramolecular, TCK-specific step and a charge-facilitated, but pH-independent, membrane association step. Membrane association of TCK may, together with microtubule association (Tombes, R.M., Farr, A., and Shapiro, B.M. (1988) Exp. Cell Res. 178, 307-317) represent a mechanism required for specific accumulation of the enzyme within the flagellum.
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PMID:Membrane association of flagellar creatine kinase in the sperm phosphocreatine shuttle. 168 Aug 67

Several mechanisms are used to control the behaviour of sea urchin spermatozoa while fertilizing eggs. These include discrete regulatory steps that modulate the sperm activation sequence from spawning to gamete membrane fusion. After release from the testis, sperm motility is instantaneously activated, by using intracellular pH as a throttle mechanism to control the rate of the dynein motor that catalyses axonemal bending. To support motility, energy is transported from the mitochondrion to the tail, by using a shuttle mechanism involving phosphocreatine diffusion. This shuttle employs a novel, endotriplicated, creatine kinase of Mr 140,000 in the flagellar axoneme as its terminus. The steering mechanism that determines where the spermatozoon swims is unknown, but may involve an egg peptide-induced guanylate cyclase activation, mediated by a cGMP-dependent Ca2+ channel, and attenuated by a plasma membrane cGMP phosphodiesterase. Upon arriving at the egg, which is identified by virtue of its proteoglycan coat (egg jelly), the spermatozoon undergoes a univesicular secretion that prepares it to fuse with the egg. This acrosome reaction involves several altered ionic fluxes in its mechanism, terminating in a massive Ca2+ uptake. If the spermatozoon is fortunate enough to fuse with an egg, a new member of the species is generated; if the acrosome reaction occurs without gamete fusion, the spermatozoon rapidly dies. All of these activation processes involve changes in the intracellular ionic milieu that are co-ordinated with altered enzyme activities, often in a causal fashion. Even with our current imperfect understanding of the process, a few of the steps in sperm activation may be defined by biochemical pathways that include specific modulatory control points.
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PMID:Molecular mechanisms of sea-urchin sperm activation before fertilization. 196

Improvement of preservation with cardioplegic solution by nitroglycerin-induced delayed preconditioning was studied in the isolated rat heart. The isolated rat heart was arrested using St. Thomas Hospital solution, and then reperfused with normothermic Krebs-Henseleit solution for 40 min after a 4-h hypothermic ischemic period. Heart rate, coronary flow, left ventricular pressure and the maximum value of the first derivatives of left ventricular pressure (+/-dp/dt(max)) were recorded, and plasma concentrations of CGRP-like immunoreactivity (CGRP-LI) and nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha) in myocardial tissues, and creatine kinase in coronary effluent were measured. Delayed preconditioning was induced by i.v. injection of nitroglycerin 24 h before the experiment. Nitroglycerin (60 microg/kg or 120 microg/kg) caused an improvement of cardiac function, a decrease in the release of creatine kinase in coronary effluent and a decrease in the content of TNF-alpha in myocardial tissues. Nitroglycerin significantly increased plasma concentrations of CGRP and NO. After pretreatment with capsaicin, which depletes neurotransmitters in sensory nerves, or methylene blue, a selective guanylate cyclase inhibitor, the protection and the elevated release of CGRP induced by nitroglycerin were abolished. The present study suggests that improvement of preservation with cardioplegic solution by nitroglycerin-induced delayed preconditioning is due to stimulation of CGRP release in the rat heart, and that the protection of CGRP-mediated nitroglycerin is related to inhibition of TNF-alpha production.
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PMID:Improvement of preservation with cardioplegic solution by nitroglycerin-induced delayed preconditioning is mediated by calcitonin gene-related peptide. 1174 39

Previous studies have shown that heme oxygenase-1 (HO-1), a heat stress protein (HSP32), has a beneficial effect on the ischemic myocardium. The purpose of the present study was to explore whether HO-1 is involved in delayed cardioprotection provided by heat stress in vivo. Sprague--Dawley rats were pretreated with whole body hyperthermia (rectal 42 degrees C) for 15 min followed by ischemia-reperfusion 24 h later. Ischemia-reperfusion injury was induced by 45 min of coronary artery occlusion followed by a 3-h reperfusion. Myocardial injury degree was evaluated by measurement of infarct size and serum creatine kinase (CK) activity. The expression of HO-1 mRNA and protein in myocardial tissues were measured. Pretreatment with hyperthemia significantly reduced infarct size and CK release during reperfusion, which was completely blocked by pretreatment with ZnPP-9, an inhibitor of HO and methylene blue, an inhibitor of soluble guanylate cyclase. Heat stress also significantly increased the expression of HO-1 mRNA and protein, and the effect was not affected by pretreatment with methylene blue. The present results suggest that the HO-1 pathway is involved in the mediation of delayed cardioprotection by heat stress in rats.
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PMID:Heme oxygenase-1 pathway is involved in delayed protection induced by heat stress against cardiac ischemia-reperfusion injury. 1185 99

Previous investigations have demonstrated that early preconditioning induced by nitroglycerin is mediated by calcitonin gene-related peptide (CGRP). In the present study, we addressed the question of whether delayed preconditioning induced by nitroglycerin in the rat is related to stimulation of the release and synthesis of CGRP. Sprague-Dawley rats were pretreated with nitroglycerin 24 h before the experiment. The left main coronary artery was occluded for 60 min, followed by 3 h reperfusion. Infarct size, serum creatine kinase activity, serum levels of NO and CGRP and the expression of alpha- and beta-CGRP isoform mRNA in lumbar dorsal root ganglia were measured. Pretreatment with nitroglycerin (60 or 120 microg/kg i.v.) reduced both the infarct size and the release of creatine kinase during reperfusion and caused a significant increase in the expression of alpha-CGRP mRNA, but not beta-CGRP mRNA, concomitantly with an increase in concentrations of NO and CGRP. The increase in CGRP expression preceded the increase in CGRP release. The effects of nitroglycerin were abolished completely by pretreatment with methylene blue (30 mg/kg i.p.), an inhibitor of guanylate cyclase, or capsaicin (50 mg/kg s.c.), which selectively depletes transmitters in capsaicin-sensitive sensory nerves. The present results suggest that the delayed cardioprotection induced by nitroglycerin is mediated mainly by the alpha-CGRP isoform via the NO-cGMP pathway.
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PMID:Delayed cardioprotection induced by nitroglycerin is mediated by alpha-calcitonin gene-related peptide. 1191 48

Adenylyl cyclases (ACs) synthesize cAMP and are present in cells as transmembrane AC and soluble AC (sAC). In sperm, the cAMP produced regulates ion channels and it also activates protein kinase-A that in turn phosphorylates specific axonemal proteins to activate flagellar motility. In mammalian sperm, sAC localizes to the midpiece of flagella, whereas in sea urchin sperm sAC is along the entire flagellum. Here we show that in sea urchin sperm, sAC is complexed with proteins of the plasma membrane and axoneme. Immunoprecipitation shows that a minimum of 10 proteins is tightly associated with sAC. Mass spectrometry of peptides derived from these proteins shows them to be: axonemal dynein heavy chains 7 and 9, sperm specific Na+/H+ exchanger, cyclic nucleotide-gated ion channel, sperm specific creatine kinase, membrane bound guanylyl cyclase, cyclic GMP specific phosphodiesterase 5A, the receptor for the egg peptide speract, and alpha- and beta-tubulins. The sAC-associated proteins could be important in linking membrane signal transduction to energy utilisation in the regulation of flagellar motility.
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PMID:Proteins associated with soluble adenylyl cyclase in sea urchin sperm flagella. 1684 96

We showed recently that mitochondrial ATP-dependent K(+) channel (mitoK(ATP)) opening is required for the inotropic response to ouabain. Because mitoK(ATP) opening is also required for most forms of cardioprotection, we investigated whether exposure to ouabain was cardioprotective. We also began to map the signaling pathways linking ouabain binding to Na(+)-K(+)-ATPase with the opening of mitoK(ATP). In Langendorff-perfused rat hearts, 10-80 microM ouabain given before the onset of ischemia resulted in cardioprotection against ischemia-reperfusion injury, as documented by an improved recovery of contractile function and a reduction of infarct size. In skinned cardiac fibers, a ouabain-induced protection of mitochondrial outer membrane integrity, adenine nucleotide compartmentation, and energy transfer efficiency was evidenced by a decreased release of cytochrome c and preserved half-saturation constant of respiration for ADP and adenine nucleotide translocase-mitochondrial creatine kinase coupling, respectively. Ouabain-induced positive inotropy was dose dependent over the range studied, whereas ouabain-induced cardioprotection was maximal at the lowest dose tested. Compared with bradykinin (BK)-induced preconditioning, ouabain was equally efficient. However, the two ligands clearly diverge in the intracellular steps leading to mitoK(ATP) opening from their respective receptors. Thus BK-induced cardioprotection was blocked by inhibitors of cGMP-dependent protein kinase (PKG) or guanylyl cyclase (GC), whereas ouabain-induced protection was not blocked by either agent. Interestingly, however, ouabain-induced inotropy appears to require PKG and GC. Thus 5-hydroxydecanoate (a selective mitoK(ATP) inhibitor), N-(2-mercaptopropionyl)glycine (MPG; a reactive oxygen species scavenger), ODQ (a GC inhibitor), PP2 (a src kinase inhibitor), and KT-5823 (a PKG inhibitor) abolished preconditioning by BK and blocked the inotropic response to ouabain. However, only PP2, 5-HD, and MPG blocked ouabain-induced cardioprotection.
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PMID:Ouabain protects rat hearts against ischemia-reperfusion injury via pathway involving src kinase, mitoKATP, and ROS. 1709 31

Methylene blue (MB), generic name methylthioninium (C(16)H(18)ClN(3) S . 3H(2)O), is a blue dye synthesized in 1876 by Heinrich Caro for use as a textile dye and used in the laboratory and clinically since the 1890s, with well-known toxicity and pharmacokinetics. It has experimentally proven neuroprotective and cardioprotective effects in a porcine model of global ischemia-reperfusion in experimental cardiac arrest. This effect has been attributed to MB's blocking effect on nitric oxide synthase and guanylyl cyclase, the latter blocking the synthesis of the second messenger of nitric oxide. The physiological effects during reperfusion include stabilization of the systemic circulation without significantly increased total peripheral resistance, moderately increased cerebral cortical blood flow, a decrease of lipid peroxidation and inflammation, and less anoxic tissue injury in the brain and the heart. The last two effects are recorded as less increase in plasma concentrations of astroglial protein S-100beta, as well as troponin I and creatine kinase isoenzyme MB, respectively.
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PMID:Neuro- and cardioprotective effects of blockade of nitric oxide action by administration of methylene blue. 1807 76

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