Disease relevance of H-7

• MDL 27,032 was more potent than H-7 for the inhibition of metastasis but was significantly less potent than staurosporine [1].
• Repeated administration of PKC inhibitors chelerythrine and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride with DAMGO did not alter the tolerance to DAMGO; however, dependence (defined as naloxone-induced withdrawal hyperalgesia) was blocked [2].
• The effect of the protein kinase C enzyme inhibitor H-7 on the noncardiogenic lung edema induced by phorbol myristate acetate (PMA) in mice was examined [3].
• Bleb formation induced by VP and PDB was accompanied by an extensive redistribution of filamentous actin from the pericanalicular area to the cell body, and this effect was fully prevented by H-7 [4].
• We have studied the effect of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), a protein kinase inhibitor, on the regulation of apoptosis in the human neuroblastoma cell line, SH-SY5Y [5].

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

• Interestingly, C3 mRNA induced by Newcastle disease virus or inactivated Newcastle disease virus was inhibited by protein kinase inhibitors, H-7 and staurosporine, whereas these inhibitors had no effect on C3 induction mediated by LPS or cytokines, indicating the existence of different signal transduction pathways [12].
• This effect was abolished by the PKC inhibitors H-7 and bisindolylmaleimide I while pertussis toxin failed to block stimulation [13].
• In C6 glioma cells, W-7 and not H-7 inhibited dose-dependently acid sphingomyelinase, a result indicating the modulation of this lysosomal enzyme by a calmodulin-dependent system [14].
• Previously, we reported that the protein kinase inhibitor H7 partially reverses Adriamycin resistance in the multidrug resistant (MDR) murine fibrosarcoma line UV-2237M-ADRR [15].
• The enhancement of formalin nociceptive behaviours (hyperalgesia) in rats treated with L-glutamate or substance P was reversed by pretreatment with inhibitors of nitric oxide (L-NAME), arachidonic acid (dexamethasone) or protein kinase C (H-7) [16].

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

• Inhibition of protein kinase C activity by prolonged stimulation with phorbol 12-myristate 13-acetate or the protein kinase inhibitor H7 prior to irradiation attenuated the increase in EGR1 and JUN transcripts [31].
• Interleukin-6 (IL-6) activation of the immediate-early gene junB has been shown to require both a tyrosine kinase and an unknown 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7)-sensitive pathway [32].
• H-7 inhibited colony formation of ME-1 cells by IL-3 or GM-CSF dose dependently, but had little inhibitory effect on colony formation by IL-4 [33].
• Staurosporine and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine inhibited PDT mediated c-fos activation while N-(2-guanidinoethyl)-5-isoquinoline-sulfonamide had no effect [34].
• The protein kinase C inhibitor H-7, however, was not effective in inhibiting phosphatidylcholine hydrolysis in response to human IL-3 in NIH 3T3 cells expressing the human receptor [35].

Analytical, diagnostic and therapeutic context of H-7

• We have previously shown that intraperitoneal injection of H-7, an inhibitor of PKC, restores completely the activity of Na(+)-K(+)-ATPase in sciatic nerve of diabetic mice; however, the effect was transient, with a half-life of approximately 1 h under the conditions used [36].
• Two-dimensional peptide mapping following tryptic hydrolysis revealed that H-7 selectively inhibited the protein kinase C-catalyzed phosphorylation of myosin light chain [37].
• Electron microscopy confirmed that H-7 does not abolish the formation of adherens-type junctions, suggesting that phosphorylation plays a different role in the assembly of tight junctions versus adherens-type junctions [38].
• Tyrosine phosphorylation of focal contacts was highly sensitive to cellular contractility, and was diminished within 5 minutes after treatment with the kinase inhibitor H-7, an inhibitor of actomyosin contractility [39].
• Immunofluorescence microscopy showed that H-7 confers Ca2+ independence on cultured epithelial lens cells, which lack tight junctions and desmosomes but have microfilament-associated adherens junctions [40].

References