Disease relevance of K00203

• Administration of bisindolylmaleimide VIII to rats during autoantigen stimulation prevented the development of symptoms of T cell-mediated autoimmune diseases in two models, the Lewis rat model of experimental allergic encephalitis and the Lewis adjuvant arthritis model [1].
• RESULTS: Neither bisindolylmaleimide nor Gö6976, which block several protein kinase C isoforms but not protein kinase C-zeta, protected against the decrease in transepithelial electrical resistance after enteropathogenic E. coli infection [2].
• Furthermore, a cell-permeable Ca2+ chelator and diverse PKC inhibitors, such as calphostin C, hypericin, chelerythrine, and bisindolylmaleimide, inhibited CSC-enhanced metastasis [3].
• These effects could not be reproduced by treatment with 1,2DOG before anoxia or during anoxia or by a two-step treatment with the PKC-inactive 1,3-dioctanoyl-sn-glycerol and were fully abolished with 1 micromol/L bisindolylmaleimide (PKC inhibitor) [4].
• This inhibitory effect was largely prevented by the pertussis toxin but was insensitive to inhibitors of protein kinase C bisindolylmaleimide and protein kinase A H-89 [5].

High impact information on K00203

• Thus, the use of agents such as bisindolylmaleimide VIII may be therapeutically useful for supporting more effective elimination of detrimental cells through enhancement of Fas-dependent apoptosis signaling [1].
• Bisindolylmaleimide VIII facilitates Fas-mediated apoptosis and inhibits T cell-mediated autoimmune diseases [1].
• Bisindolylmaleimide VIII (Bis VIII), a PKC inhibitor, can sensitize T cells for death receptor-induced apoptosis and thus can inhibit the development of T cell-mediated autoimmune disease in vivo [6].
• In contrast, inhibition of PKC activity by bisindolylmaleimide and related compounds had no perceptible effect on growth cone motility, but completely blocked phorbol ester effects [7].
• Treatment of mouse or human cells with the protein kinase C (PKC) inhibitors H7 or bisindolylmaleimide I induced an increase in the lifetime of p53, leading to its accumulation [8].

Chemical compound and disease context of K00203

• Accordingly, the PKC inhibitor bisindolylmaleimide inhibited the oxidative burst induced by either PMA or intact pseudomonas, but not by fMLP, whereas the p38 kinase inhibitor SB-203580 fully inhibited the respiratory burst induced by fMLP or the PlcHR-replete wild-type bacteria, but not PMA or the PlcHR-deficient DeltaHR bacterial mutant [9].
• Both the gene transfer of estrogen receptor alpha using adenovirus and treatment with the protein kinase C inhibitor bisindolylmaleimide I significantly enhanced the effects of 17beta-E2 treatment under high-glucose conditions, whereas these effects were abolished by the estrogen receptor antagonist ICI 182,780 (faslodex) [10].
• The depression of the Ca2+ channel current by interleukin-1 beta was prevented by the extracellular application of pertussis toxin, and by the intracellular application of GDP[beta S], H-7, staurosporine or bisindolylmaleimide [11].
• METHODS: Burkitt's lymphoma cells (Raji and Daudi) were treated with the PK-C inhibitor, bisindolylmaleimide (BIM), or the CaM inhibitor, trifluoperazine (TFPZ), in a dose-dependent manner and in a time-dependent manner [12].
• In addition, inhibition of protein kinase C by bisindolylmaleimide 1 or protein kinase C beta peptide inhibitor had no effect on the methoxamine-induced antagonism of I(Ca-L) in the absence or presence of hypoxia [13].

Biological context of K00203

• This phosphorylation was not blocked by the protein kinase C (PKC) inhibitor bisindolylmaleimide, which reduced the extent of aggregation and calcium increase [14].
• In marked contrast, perturbations in the PKC/Raf/MAPK pathway played an integral role in LC/BRY-mediated cell death based on evidence that pretreatment of cells with bisindolylmaleimide I, a selective PKC inhibitor, or geldanamycin, a benzoquinone ansamycin, which destabilizes and depletes Raf-1, markedly suppressed apoptosis [15].
• Furthermore, following down-regulation, the effect of vasopressin was still blocked by the PKC inhibitors, Ro-31-8220 and bisindolylmaleimide [16].
• Down-regulation of diacylglycerol-sensitive types of protein kinase C (PKC) by pretreatment with phorbol 12-myristate 13-acetate or inhibition with bisindolylmaleimide prevented the DA-mediated increase in Na,K-ATPase activity and exocytosis of Na,K-pumps to the BLM [17].
• Several of the fluorescent bisindolylmaleimide derivatives (fim-1, fim-2, and rim-1) acted as ATP-competitive catalytic site inhibitors and retained much of the potency and specificity of the parental compound [18].

Anatomical context of K00203

• These changes persisted in isolated adipocytes from the transgenic mice and were rescued by the protein kinase C inhibitor bisindolylmaleimide [19].
• Expression of c-FLIP(L) and resistance to CD95-mediated apoptosis of monocyte-derived dendritic cells: inhibition by bisindolylmaleimide [20].
• A broad-spectrum PKC inhibitor bisindolylmaleimide I did not have any apparent effect on the morphology of the cultures or on the number of cell junctions [21].
• PKC inhibition with Ro-31-8425 or bisindolylmaleimide I sensitized this cell line to death from menadione [22].
• At higher expression levels of GAT1 protein, a larger portion of GAT1 was found on the plasma membrane during basal level conditions and treatment with bisindolylmaleimide resulted in removal of these transporters from the plasma membrane [23].

Associations of K00203 with other chemical compounds

• The protein kinase C activator phorbol 12-myristate 13-acetate mimicked and the protein kinase C inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine and bisindolylmaleimide prevented ischemic preconditioning [24].
• The secretagogue action of GnRH is not very sensitive to bisindolylmaleimide I, an inhibitor of protein kinase C, but is blocked by loading cells with a calcium chelator, 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid [25].
• The inhibitory effect of methoxamine was not mimicked by PDBu, and it persisted in the presence of bisindolylmaleimide, a selective PKC inhibitor [26].
• PACAP caused G-protein- and phospholipase C-mediated calcium release from inositol-trisphosphate-sensitive stores and subsequent protein kinase C-mediated calcium influx, demonstrated by treatment with GDP-beta-S, neomycin, U-73122, calcium-free saline, thapsigargin, bisindolylmaleimide, and chelerythrine [27].
• Intracellular dialysis with GDP-beta-S (500 microM) or with the specific inhibitors of protein kinase C (PKC), the pseudosubstrate PKC inhibitor (PKCI 19-31) (2 microM) and bisindolylmaleimide (BIS) (1 microM) significantly diminished the cortisol inhibition of the Ca2+ channel current [28].

Gene context of K00203

• Erk activity in FGF2-treated RCS (rat chondrosarcoma) chondrocytes or human primary chondrocytes was abolished by the protein kinase C inhibitor bisindolylmaleimide I (Bis I) [29].
• PMA-induced phosphorylation of the EGFR at Tyr(1068) was blocked by bisindolylmaleimide (BIM), a PKC inhibitor, and rottlerin, a PKCdelta-specific inhibitor [30].
• Inhibition of kinases upstream to MEK1/2 (PI-3K, PKC, and CaMKII) by administration of LY294002, bisindolylmaleimide, or KN-62, respectively, also reversed clozapine-induced suppression of CAR [31].
• Importantly, inhibition of ET-1 constriction by Bis occurred in 24 months but not 4 months (p<0.01) [32].
• PMA-stimulated PLD activity was blocked by the PKC inhibitor bisindolylmaleimide [33].

Analytical, diagnostic and therapeutic context of K00203

• We have purified Fos kinase by affinity chromatography using the Sepharose-linked protein kinase inhibitor, bisindolylmaleimide (BIM) [34].
• RESULTS: Pressure-dependent constriction and constriction in response to phorbol dibutyrate in the MCAs were inhibited by PKC inhibitors (staurosporine [40 nmol/L], chelerythrine [12 micromol/L], bisindolylmaleimide [5 micromol/L]), declined with age before stroke development in SHRsp, and were absent after stroke [35].
• However, PD98059, BIM and U73122 all reduced phosphorylation of ERK1/2 determined by Western blot analysis with anti-phospho-ERK1/2 antibodies [36].
• The interaction of bisindolylmaleimide (BIM), widely used as a specific protein kinase C (PKC) inhibitor, with rat brain Kv1.5 (rKv1.5) channels stably expressed in Chinese hamster ovary cells was investigated using the whole-cell patch-clamp technique [37].
• Furthermore, immunofluorescence studies with human umbilical vein endothelial cells revealed that bisindolylmaleimide, PD-98059, and l-NMMA attenuate VEGF-induced reorganization of vascular endothelial cadherin [38].

References