Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Na(+)-dependent and -independent transport sites were elucidated for glycine and L-leucine, respectively, in Chang liver cells, a human culture cell line. Findings of acceleration of the L-leucine uptake by the cells in the acidic medium and synchronized acidification within the cell membrane vesicles with the uptake by them all suggested contransport of L-leucine and proton and the uptake of L-leucine dependent on the inward proton gradient in Chang liver cells. Cotransport of L-leucine and proton was also demonstrated in human peripheral lymphocytes and accelerated by the addition of concanavalin A, probably accompanied by membrane hyperpolarization. It was shown that the Na(+)-gradient-dependent uptake of glycine can be regulated by insulin and 17 beta-estradiol in the rat uterus and by Ca(2+)-calmodulin and membrane potential in Chang liver cells. D-Aspartate uptake as a model of glutamate transport was characterized in rat hippocampal slices and found to consist of Na(+)-dependent (higher-affinity) and -independent (lower-affinity) components. The vulnerability of hippocampal neurons to the Alzheimer beta-amyloid protein was confirmed in vitro with primary cultured rat hippocampal neurons in the presence of the amyloid protein beta 1-42 or its core fragments. The toxicity of the amyloid protein could be blocked by the addition of insulin and several other growth factors to the medium. The addition of genipin, a plant-derived iridoid, was demonstrated to prevent the toxicity of a synthetic fragment of beta 1-42, beta 25-35. Genipin had a neuritogenic activity in PC12h cells, a rat pheochromocytoma cell line, an activity extremely sensitive to inhibitors of the nitrogen oxide (NO) synthase and soluble guanylate cyclase and an NO scavenger. It was also demonstrated in PC12h cells that the activation of the MAP kinase cascade was essential for the neuritogenesis of genipin. These properties of genipin are very comparable to those of nerve growth factor in the cells. It is considered likely that various useful, neurotrophic substances and their extracts will be found in plants in future.
 ...
PMID:[Studies on the cytological function of the biomembrane and the neurons]. 1240 Jan 54

We have demonstrated previously that a natural iridoid compound, genipin, induced neuritogenesis through activation of nitric oxide synthase (NOS) and mitogen-activated protein kinase (MAPK) in PC12h cells. In this paper, we investigated whether cyclic GMP (cGMP) and cGMP-dependent protein kinase (PKG) are involved in the neuritogenesis as a result of NOS activation. Furthermore, we also investigated the relationship between cGMP and MAPK activation in the signaling pathway. The genipin-induced neuritogenesis accompanied by induction of neurofilament was significantly inhibited by 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ) and KT5823, inhibitors of soluble guanylate cyclase and PKG, respectively. Genipin-induced MAPK phosphorylation was also abolished by ODQ. These inhibitory effects of ODQ were similar to those observed for nerve growth factor (NGF)-induced neurite outgrowth and MAPK phosphorylation. The membrane-permeable cGMP analog, 8-Bromo-cGMP, had prominent neuritogenic activity, which was completely inhibited by a MAPK kinase inhibitor, PD98059. These results suggest that the soluble guanylate cyclase-PKG signaling pathway is important for MAPK activation by genipin as well as NGF during neuritogenesis in PC12h cells.
 ...
PMID:Cyclic GMP-dependent neurite outgrowth by genipin and nerve growth factor in PC12h cells. 1504 33

We have reported previously that genipin, a natural iridoid compound, induces neuritogenesis through a nitric oxide (NO)-cyclic GMP (cGMP)-cGMP-dependent protein kinase (PKG) signaling pathway in PC12h cells and that neuronal NO synthase (nNOS) is one of the target molecules of genipin in vitro. Recently, it has been suggested that the neurotrophic effects of NO are due to its direct activation of receptor-tyrosine kinase, especially TrkA. In this study, we investigated whether mouse neuroblastoma Neuro2a cells, which express nNOS but not TrkA, respond to genipin with neurite outgrowth through the mechanism observed in PC12h cells, to assess the involvement of TrkA in the mechanism. Neuro2a cells expressed all three types of NO synthase (NOS), and nNOS was detectable as the main component in Western blot analysis. Genipin significantly induced neurite outgrowth and activation of NADPH-diaphorase, which were significantly blocked by a non-selective NOS inhibitor. Both a soluble guanylate cyclase inhibitor and a PKG inhibitor also inhibited the genipin-induced neuritogenesis. Genipin induced sustained phosphorylation of mitogen-activated protein kinase (MAPK). In fact, the genipin-induced neurite outgrowth was completely inhibited by a specific MAPK kinase inhibitor. Moreover, a NOS inhibitor abolished MAPK phosphorylation as well as neurite outgrowth in genipin-treated cells. These results suggest that genipin induces neurite outgrowth through an NO-cGMP-PKG signaling pathway followed by MAPK phosphorylation without TrkA activation in Neuro2a cells and that PKG downstream to NOSs, which may be mainly nNOS, is very important for the signaling molecule to induce neuritogenesis by genipin.
 ...
PMID:Genipin exhibits neurotrophic effects through a common signaling pathway in nitric oxide synthase-expressing cells. 1817 84