Disease relevance of HA 1004

• 3-methyl H7 decreased the PMA-induced expression of BLV in NBC-13 cells in a dose-dependent manner, whereas HA1004 did not inhibit this expression [1].
• Protein kinase C inhibitor staurosporine, but not cyclic nucleotide-dependent protein kinase inhibitor HA-1004, also dramatically reduced constitutive levels of nuclear NF kappa B. Finally, TPA addition to monocytes infected with HIV-1 inhibited HIV-1 replication, as determined by reverse transcriptase assays, in a concentration-dependent manner [2].
• Nur77 nuclear import and its NBRE-binding activity in thymic lymphoma cells are regulated by different mechanisms sensitive to FK506 or HA1004 [3].
• We sought to determine whether apoptosis could be modulated by two kinds of inhibitor of protein kinases, H7 and HA1004, in concentrations that are below their toxicity limits [4].
• HA1004, an intracellular calcium antagonist, selectively attenuates pulmonary hypertension in newborn lambs [5].

High impact information on HA 1004

• The half-life of TNF mRNA was significantly decreased in the presence of protein kinase inhibitors H-7 and staurosporine, but not in the presence of HA1004 [6].
• Their ability to inhibit CD11b/CD18-independent ingestion may be mediated by cAMP, as shown by experiments with a protein kinase A inhibitor HA1004 and by direct measurement of cAMP levels in immune complex- and FMLP-stimulated PMN [7].
• First, the velocity of dynein-driven microtubule sliding in spoke-deficient mutants (pf14, pf17) was increased to wild-type level after treatment with the kinase inhibitors HA-1004 or H-7 or by the specific peptide inhibitors of cAMP-dependent protein kinase (cAPK) PKI(6-22)amide or N alpha-acetyl-PKI(6-22)amide [8].
• The cyclic nucleotide-dependent PK inhibitor HA 1004 did not inhibit IL-3-induced bcl-2 mRNA [9].
• The PKC inhibitors (H-7, staurosporine, and calphostin C), but not HA-1004, inhibited TNF-induced uPA expression, synthesis, and secretion in a dose-dependent manner [10].

Chemical compound and disease context of HA 1004

• The cyclic GMP-dependent protein kinase and cyclic AMP-dependent protein kinase inhibitor N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA1004) did not inhibit either BLV expression or blastogenesis of BLV-infected bovine PBMC [1].
• In apoptosis-resistant cells, ionomycin-induced Nur77 strongly binds DNA during the first 2 h of response, in contrast to lymphoma cells treated with ionomycin together with FK506 or HA1004, which undergo massive apoptosis [3].
• Hyperthermia increased greatly the suppressive activity of H-7 and H-8 but not that of HA1004 [11].
• In newborn lambs with pulmonary hypertension, HA1004, an intracellular calcium antagonist, is more selective and potent than nifedipine, a calcium entry blocker, in decreasing PAP and therefore may be useful in treatment of children with pulmonary hypertension [5].
• We studied the hemodynamic effects of intravenous (i.v.) infusions of HA1004 (0.1-2.0 mg/kg) in vivo in 8 newborn lambs, at rest and during pulmonary hypertension induced either by the i.v. infusion of U46619, a thromboxane A2 (TXA2) mimic, or by alveolar hypoxia [5].

Biological context of HA 1004

• In contrast, 6-h exposures to the nonspecific protein kinase inhibitor hypericin (0.1 to 100 microM) or to the nonspecific inhibitor of protein kinase A, HA1004 (50 microM), were without effect on DNA fragmentation [12].
• The protein kinase A/G inhibitor HA1004 also decreased spleen T cell apoptosis [13].
• In contrast, inhibition of cyclic nucleotide-dependent protein kinases with HA1004 had no effect on Op18 phosphorylation [14].
• Protein kinase A activity of cultured hepatocytes was specifically inhibited by H8 and HA1004 in a concentration-dependent manner, but not by H7, and there was an inverse correlation observed between potentiation of PAH-induced aldh3 gene expression and inhibition of specific PKA activity by the PKA inhibitors [15].
• H-7 exerted a dose-related suppression of antibody-dependent cell-mediated cytotoxicity (ADCC) suggesting that NK-CMC and ADCC share the utilization of PKC, however, HA1004 did not inhibit ADCC [16].

Anatomical context of HA 1004

• A protein kinase A inhibitor HA 1004 could inhibit the IL-1-induced lymphocyte penetration, where as protein kinase C (N-(2-guamidino-ethyl)-5-isoquinolinesyl foamide hydrocloride) and calcium-calmodulin (N-(6-aminohexyl)-5-chloro-1-naphthalensulfanamide) inhibitors had no effect [17].
• When cells were allowed to spread for 1h and then treated with kinase inhibitors H7 and HA1004 for 2h, IRM indicated a reduction in focal adhesion formation at concentrations where protein kinase C (PKC) should be inhibited [18].
• Here we show by measuring the transepithelial resistance that, in addition to H-7, H-8 and staurosporine can also significantly block the assembly of tight junctions, whereas HA1004 is poorly active [19].
• In contrast, HA 1004, which blocks protein kinase A and protein kinase G activity, was relatively ineffective even at high concentrations, suggesting that the activity of protein kinase C is a primary mechanism of EP-induced murine B-cell proliferation [20].
• Re-epithelialization rates were similar to control corneas when the incubation medium contained HA1004 (100 mumol/l), an analogue of H-7 that is a potent inhibitor of cyclic adenosine monophosphate- and cyclic guanosine monophosphate-dependent protein kinases and a weak inhibitor of PKC [21].

Associations of HA 1004 with other chemical compounds

• The induction of TNF transcripts by TPA was inhibited by the isoquinolinesulfonamide derivative H7 but not by HA1004, suggesting that this effect of TPA is mediated by activation of protein kinase C. TPA treatment also resulted in increased arachidonic acid release [22].
• In contrast, protein kinase C/cAMP-dependent kinase inhibitors (such as, C-I, H-7, HA-1004, KT5720, and Staurosporine) markedly decreased rMCAF induced chemotaxis suggesting the involvement of a serine/threonine protein kinase, possibly protein kinase C, in rMCAF signaling pathway [23].
• In these studies we confirmed that H7, but not HA1004, potently blocks the induction of zif268 and c-fos mRNA by nerve growth factor, carbachol, phorbol ester, Ca2+ ionophore, or forskolin [24].
• Anti-Fas antibody alone induced apoptosis in less than 20% of the cultured hepatocytes, whereas all cells were killed within 24 h by anti-Fas antibody in the presence of actinomycin D, cycloheximide, or protein kinase C (PKC) inhibitors such as H-7 and HA1004 [25].
• This effect was blocked by the A2A receptor antagonist ZM241385 and by the protein kinase C inhibitor chelerythrine, but not by the protein kinase A inhibitor N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA 1004) [26].

Gene context of HA 1004

• The effects of rIL-1 alpha and TGF-beta in combination were also unaltered by HA1004, staurosporine, and chronic phorbol ester exposure [27].
• The TCC-mediated MBP mRNA decay was completely abrogated by HA1004, an inhibitor for the cAMP- and cGMP-dependent protein kinases, but not by H7, a protein kinase C inhibitor [28].
• The TNFR60-associated protein kinase activity is inhibited by staurosporine, but not by the protein kinase A and C inhibitors, HA-1004 and H7 [29].
• The effects of PDGF, EGF, and bFGF were inhibited by H-7 or staurosporine, inhibitors of protein kinase C (PKC), but not by HA1004 with a much weaker inhibitory activity, suggesting the involvement of PKC for the activation of the protooncogenes.(ABSTRACT TRUNCATED AT 250 WORDS)[30]
• HA1004, an inhibitor of PKA, reduced the IL-1 and IL-6 levels by 29 and 27%, respectively [31].

Analytical, diagnostic and therapeutic context of HA 1004

• Dose-dependent reductions in arterial pressure of SHR were demonstrated after intravenous injection of staurosporine and HA1004 [32].
• The non-specific protein kinase inhibitor, HA-1004, and the preferential calmodulin inhibitor, W-7, had no significant effects on either morphine-induced analgesia or the inhibitory actions of exposure to the magnetic fields [33].
• High-performance liquid chromatography (HPLC) analysis of hypothalamic tissue from rats perfused with kinase inhibitors demonstrates that both calphostin-C and HA-1004 can cross the blood-brain barrier when administered peripherally [34].
• In contrast, HA1004 , an inhibitor of cyclic nucleotide-dependent protein kinase, had no effect on P. gingivalis fimbriae-induced Fc rosette formation or CD11b expression [35].
• Using a HaCaT keratinocyte cell line, Northern blotting was performed for analyzing the human MT-IIA mRNA expression levels in combination with BT and a number of protein kinase (PK) inhibitors including H7, HA1004 and a PKC-specific inhibitor chelerythrin [36].

References