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Chemical Compound Review

H-7     5-(2-methylpiperazin-1...

Synonyms: SGCUT00137, SureCN190590, AG-D-25603, BSPBio_001105, KBioGR_000445, ...
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Disease relevance of H-7


Psychiatry related information on H-7

  • Amnesia induced by TFP, W-13, and H-7 injected into the LPO occurred significantly later than amnesia produced when these agents were injected into the IMHV [6].

High impact information on H-7

  • Here we report that micromolar levels of OAG and phorbol esters depress Ca2+ currents in chick sensory neurons independently of their effect as activators of protein kinase C. The depression of the Ca2+ current is rapid and is unaffected by intracellular application of the protein kinase C inhibitors staurosporin, sphingosine and H-7 [7].
  • We have found that intracellular injection into CA1 pyramidal cells of the protein kinase inhibitor H-7, or of the calmodulin antagonist calmidazolium, blocks LTP [8].
  • Here we test whether the persistent signal in LTP is an enduring phosphoester bond, a long-lived kinase activator, or a constitutively active protein kinase by using H-7, which inhibits activated protein kinases and sphingosine, which competes with activators of PKC (ref. 17) and CaMKII (ref. 18) [9].
  • These results, together with the fact that the protein kinase inhibitor H7 resulted in both a dose-dependent inhibition of gag/v-erbA protein phosphorylation and the induction of terminal differentiation of AEV-transformed erythroblasts show that phosphorylation of gag/v-erbA protein is required for full biological activity [10].
  • Phenylephrine-induced c-fos mRNA was partially inhibited by H-7, a protein kinase C inhibitor, and by nifedipine, a Ca2+ channel blocker; these two compounds together had additive effects [11].

Chemical compound and disease context of H-7


Biological context of H-7

  • ANG II-induced ppET-1 gene expression was completely blocked by protein kinase C inhibitor H-7 or by down-regulation of endogenous protein kinase C by pretreatment with phorbol ester [17].
  • Pretreatment of FSC with H-7, a protein kinase C inhibitor, blocked cytokine-induced increase in both MCP-1 gene expression and secretion [18].
  • Within 30 min of contact, action potential-evoked calcium accumulation was reversibly augmented from 228 +/- 82 nM to 803 +/- 212 nM, an action that was blocked by H-7 (40-100 microM) [19].
  • However, the disruption of cell-cell contacts, the cell shape changes, and the redistribution of cingulin and other junctional proteins induced by LC were inhibited when cells were pretreated with the protein kinase inhibitor H-7 (greater than or equal to 30 microM) [20].
  • The IC50 of Gö 6976 shows a 12- to 60-fold more potent effect than for H-7, another PKC inhibitor with a similar mechanism [21].

Anatomical context of H-7

  • These alterations were not blocked by the protein kinase C inhibitor H-7, which did inhibit TPA-induced T cell attachment to fibronectin [22].
  • It was found that HpaII site H-7 in the CpG island of the X-chromosome-linked Pgk-1 gene is less than or equal to 10% methylated in oocytes and male embryos but becomes 40% methylated in female embryos at 6.5 days; about the time of X-chromosome inactivation of the inner cell mass [23].
  • Endothelial cells treated with TNF acquire the ability to invade extracellular matrix and reorganize into tube-like structures when grown on Matrigel-coated culture dishes, a behavior blocked by H-7, but not by HA 1004 [24].
  • Neither H-7 nor staurosporine had any effect on CFU-E formation [25].
  • H-7 and staurosporine dose-dependently inhibited the protein kinase C from K562 cells [25].

Associations of H-7 with other chemical compounds

  • High glucose concentrations induced a sustained activation of protein kinase C (PKC) in VSMC, which was prevented by coincubation with H-7 [26].
  • In contrast, neither H-7 nor HA1004 had an effect on growth inhibition induced by human natural IFN-alpha treatment [27].
  • CONCLUSIONS: H-7 and polymyxin B did not blunt the reduction in infant size achieved with ischemic preconditioning [28].
  • The two actions of PKC stimulators were blocked by PKC inhibitors (staurosporine, a pseudosubstrate peptide, and H-7), but SP- and LHRH-mediated suppression of IM and receptor desensitization were not affected [29].
  • Activation was time and dose dependent, exhibited a biphasic pattern, and was blocked by anti-prolactin antiserum, by PKC inhibitors such as 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) and sphingosine, and by cyclosporine [30].

Gene context of H-7


Analytical, diagnostic and therapeutic context of H-7


  1. Inhibition of experimental metastasis and cell adhesion of B16F1 melanoma cells by inhibitors of protein kinase C. Dumont, J.A., Jones, W.D., Bitonti, A.J. Cancer Res. (1992) [Pubmed]
  2. Dissociation of tolerance and dependence for opioid peripheral antinociception in rats. Aley, K.O., Levine, J.D. J. Neurosci. (1997) [Pubmed]
  3. Inhibition of induced acute lung edema by a novel protein kinase C inhibitor. Struhar, D., Harbeck, R.J. FASEB J. (1987) [Pubmed]
  4. Vasopressin-induced disruption of actin cytoskeletal organization and canalicular function in isolated rat hepatocyte couplets: possible involvement of protein kinase C. Roma, M.G., Stone, V., Shaw, R., Coleman, R. Hepatology (1998) [Pubmed]
  5. 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine induces apoptosis in human neuroblastoma cells, SH-SY5Y, through a p53-dependent pathway. Ronca, F., Chan, S.L., Yu, V.C. J. Biol. Chem. (1997) [Pubmed]
  6. Protein kinase inhibitors disrupt memory formation in two chick brain regions. Serrano, P.A., Rodriguez, W.A., Bennett, E.L., Rosenzweig, M.R. Pharmacol. Biochem. Behav. (1995) [Pubmed]
  7. A diacylglycerol analogue reduces neuronal calcium currents independently of protein kinase C activation. Hockberger, P., Toselli, M., Swandulla, D., Lux, H.D. Nature (1989) [Pubmed]
  8. An essential role for postsynaptic calmodulin and protein kinase activity in long-term potentiation. Malenka, R.C., Kauer, J.A., Perkel, D.J., Mauk, M.D., Kelly, P.T., Nicoll, R.A., Waxham, M.N. Nature (1989) [Pubmed]
  9. Persistent protein kinase activity underlying long-term potentiation. Malinow, R., Madison, D.V., Tsien, R.W. Nature (1988) [Pubmed]
  10. Phosphorylation of the v-erbA protein is required for its function as an oncogene. Glineur, C., Zenke, M., Beug, H., Ghysdael, J. Genes Dev. (1990) [Pubmed]
  11. Alpha 1 adrenergic receptor-induced c-fos gene expression in rat aorta and cultured vascular smooth muscle cells. Okazaki, M., Hu, Z.W., Fujinaga, M., Hoffman, B.B. J. Clin. Invest. (1994) [Pubmed]
  12. Induction of C3 expression in astrocytes is regulated by cytokines and Newcastle disease virus. Rus, H.G., Kim, L.M., Niculescu, F.I., Shin, M.L. J. Immunol. (1992) [Pubmed]
  13. Oxidized low-density lipoprotein stimulates protein kinase C (PKC) and induces expression of PKC-isotypes via prostaglandin-H-synthase in P388D1 macrophage-like cells. Claus, R., Fyrnys, B., Deigner, H.P., Wolf, G. Biochemistry (1996) [Pubmed]
  14. Calmodulin antagonist W-7 inhibits lysosomal sphingomyelinase activity in C6 glioma cells. Masson, M., Albouz, S., Boutry, J.M., Spezzatti, B., Castagna, M., Baumann, N. J. Neurochem. (1989) [Pubmed]
  15. A novel N-myristylated synthetic octapeptide inhibits protein kinase C activity and partially reverses murine fibrosarcoma cell resistance to adriamycin. O'Brian, C.A., Ward, N.E., Liskamp, R.M., de Bont, D.B., Earnest, L.E., van Boom, J.H., Fan, D. Investigational new drugs. (1991) [Pubmed]
  16. Intracellular messengers contributing to persistent nociception and hyperalgesia induced by L-glutamate and substance P in the rat formalin pain model. Coderre, T.J., Yashpal, K. Eur. J. Neurosci. (1994) [Pubmed]
  17. Endothelin-1 is an autocrine/paracrine factor in the mechanism of angiotensin II-induced hypertrophy in cultured rat cardiomyocytes. Ito, H., Hirata, Y., Adachi, S., Tanaka, M., Tsujino, M., Koike, A., Nogami, A., Murumo, F., Hiroe, M. J. Clin. Invest. (1993) [Pubmed]
  18. Cultured human liver fat-storing cells produce monocyte chemotactic protein-1. Regulation by proinflammatory cytokines. Marra, F., Valente, A.J., Pinzani, M., Abboud, H.E. J. Clin. Invest. (1993) [Pubmed]
  19. Synaptic target contact enhances presynaptic calcium influx by activating cAMP-dependent protein kinase during synaptogenesis. Funte, L.R., Haydon, P.G. Neuron (1993) [Pubmed]
  20. Protein kinase inhibitors prevent junction dissociation induced by low extracellular calcium in MDCK epithelial cells. Citi, S. J. Cell Biol. (1992) [Pubmed]
  21. Gö 6976, a selective inhibitor of protein kinase C, is a potent antagonist of human immunodeficiency virus 1 induction from latent/low-level-producing reservoir cells in vitro. Qatsha, K.A., Rudolph, C., Marmé, D., Schächtele, C., May, W.S. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  22. HIV-1 infection of human T lymphocytes results in enhanced alpha 5 beta 1 integrin expression. Weeks, B.S., Klotman, M.E., Dhawan, S., Kibbey, M., Rappaport, J., Kleinman, H.K., Yamada, K.M., Klotman, P.E. J. Cell Biol. (1991) [Pubmed]
  23. Use of a HpaII-polymerase chain reaction assay to study DNA methylation in the Pgk-1 CpG island of mouse embryos at the time of X-chromosome inactivation. Singer-Sam, J., Grant, M., LeBon, J.M., Okuyama, K., Chapman, V., Monk, M., Riggs, A.D. Mol. Cell. Biol. (1990) [Pubmed]
  24. Role of protein kinase C in tumor necrosis factor induction of endothelial cell urokinase-type plasminogen activator. Niedbala, M.J., Stein-Picarella, M. Blood (1993) [Pubmed]
  25. Putative involvement of protein kinase C in proliferation of human myeloid progenitor cells. Katayama, N., Nishikawa, M., Minami, N., Shirakawa, S. Blood (1989) [Pubmed]
  26. Glucose-induced downregulation of angiotensin II and arginine vasopressin receptors in cultured rat aortic vascular smooth muscle cells. Role of protein kinase C. Williams, B., Tsai, P., Schrier, R.W. J. Clin. Invest. (1992) [Pubmed]
  27. Cyclic AMP mediates the direct antiproliferative action of mismatched double-stranded RNA. Hubbell, H.R., Boyer, J.E., Roane, P., Burch, R.M. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  28. Does ischemic preconditioning trigger translocation of protein kinase C in the canine model? Przyklenk, K., Sussman, M.A., Simkhovich, B.Z., Kloner, R.A. Circulation (1995) [Pubmed]
  29. Protein kinase C is not necessary for peptide-induced suppression of M current or for desensitization of the peptide receptors. Bosma, M.M., Hille, B. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  30. Rapid activation of protein kinase C in isolated rat liver nuclei by prolactin, a known hepatic mitogen. Buckley, A.R., Crowe, P.D., Russell, D.H. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  31. Protein kinase C mediates x-ray inducibility of nuclear signal transducers EGR1 and JUN. Hallahan, D.E., Sukhatme, V.P., Sherman, M.L., Virudachalam, S., Kufe, D., Weichselbaum, R.R. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  32. Identification of a novel interleukin-6 response element containing an Ets-binding site and a CRE-like site in the junB promoter. Nakajima, K., Kusafuka, T., Takeda, T., Fujitani, Y., Nakae, K., Hirano, T. Mol. Cell. Biol. (1993) [Pubmed]
  33. Establishment and characterization of a new human leukemia cell line derived from M4E0. Yanagisawa, K., Horiuchi, T., Fujita, S. Blood (1991) [Pubmed]
  34. Photodynamic therapy mediated induction of early response genes. Luna, M.C., Wong, S., Gomer, C.J. Cancer Res. (1994) [Pubmed]
  35. Human IL-3 receptor signaling: rapid induction of phosphatidylcholine hydrolysis is independent of protein kinase C but dependent on tyrosine phosphorylation in transfected NIH 3T3 cells. Rao, P., Kitamura, T., Miyajima, A., Mufson, R.A. J. Immunol. (1995) [Pubmed]
  36. Sustained recovery of Na(+)-K(+)-ATPase activity in sciatic nerve of diabetic mice by administration of H7 or calphostin C, inhibitors of PKC. Hermenegildo, C., Felipo, V., Miñana, M.D., Romero, F.J., Grisolía, S. Diabetes (1993) [Pubmed]
  37. Serotonin secretion from human platelets may be modified by Ca2+-activated, phospholipid-dependent myosin phosphorylation. Inagaki, M., Kawamoto, S., Hidaka, H. J. Biol. Chem. (1984) [Pubmed]
  38. Different effects of protein kinase inhibitors on the localization of junctional proteins at cell-cell contact sites. Denisenko, N., Burighel, P., Citi, S. J. Cell. Sci. (1994) [Pubmed]
  39. Molecular diversity of cell-matrix adhesions. Zamir, E., Katz, B.Z., Aota, S., Yamada, K.M., Geiger, B., Kam, Z. J. Cell. Sci. (1999) [Pubmed]
  40. Cytoskeletal involvement in the modulation of cell-cell junctions by the protein kinase inhibitor H-7. Citi, S., Volberg, T., Bershadsky, A.D., Denisenko, N., Geiger, B. J. Cell. Sci. (1994) [Pubmed]
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