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.

Abstract

Human immunodeficiency virus (HIV-1) infection is followed by a period of latency or a low-levelpersistent (LLP) necrosis factor a that leads to the inhibition of intracellular viral protein synthesis and viral shedding. G( 6976 also blocks interleukin 6-mediated posttranscriptional induction of viral proteins. The ICso of G6 6976 shows a 12-to 60-fold more potent effect than for H-7, another PKC inhibitor with a similar mechanism. The inhibitory effect is reduced when Go 6976 is not added before or within 1 hr of induction by the potent PKC activator Bryostatin 1. However, Ul cells can be grown for long periods in a nontoxic concentration of Go 6976 (300 nW, which confers virtual inhibition of HIV-1 induction without the development of resistance. Results indicate that inhibition of HIV-1 proviral induction from latent/low-level-producing infectious states with potent PKC inhibitors like (1 6976 may represent an additional and promising antiviral approach.

Expression of the High Molecular Weight Fibroblast Growth Factor-2 Isoform of 210 Amino Acids Is Associated with Modulation of Protein Kinases C δ and ε and ERK Activation

“…Because the conventional PKC isotypes ␤1 and ␥ were not found by reverse transcriptasepolymerase chain reaction in any of the cell lines used in the present study, Gö 6976 must only decrease PKC ␣ activity. At the concentrations used in the present study, any of these compounds modified cell shapes or attachment, indicating the absence of toxic effects as reported for other cell types (26,41). Gö 6976 added for 24 h to the cell medium slightly decreased ERK-1 and -2 phosphorylation whatever the doxycycline concentration (Fig.…”

“…(Calbiochem), which belongs to the group of bisindolylmaleimide derivatives, was used at the concentration of 1 M to inhibit PKC ␣, ␦, and ⑀, and rottlerin (Calbiochem), which specifically inhibits PKC ␦, was used at the concentration of 6 nM (26,27). These drugs were solubilized in Me 2 SO and used in cultures at the final concentration of 0.1% Me 2 SO.…”

The nuclear factor kappa B (NF-κB): A potential therapeutic target for estrogen receptor negative breast cancers

“…Anti-cell-proliferation activity of Go6976 may be caused by decreased NF-B activation and down-regulation of ccD1 and the subsequent cell cycle progression (7). Although the inhibitory influence of Go6976 on PKC␣ and -␤ has been well characterized (28,29), its influences on other kinases has not been documented. Thus, the inhibition by Go6976 of any one of these other kinases that are involved in the activation of NF-B, in addition to PKC, is not eliminated.…”

“…Hybond nitrocellulose membrane and ECL (enhanced chemiluminescence) immunodetection kits were obtained from Amersham Pharmacia. Go6976, a nonglyosidic indolcarbazole, and an inhibitor of protein kinase C alpha and beta was purchased from Calbiochem-Novabiochem (28,29).…”

The sarcoplasmic–endoplasmic reticulum Ca2+ ATPase 2b regulates the Ca2+ transients elicited by P2Y2 activation in PC Cl3 thyroid cells

“…To assess the involvement of PKC in the modulation of the ATP/UTP-induced [Ca 2C ] i transients (Marsigliante et al 2002), the calcium-dependent PKC inhibitor Gö 6976 and the calcium-dependent and -independent PKC inhibitor GF109203X were used (Martiny- Baron et al 1993, Qatsha et al 1993. In the absence of PKC inhibitors, the addition of ATP or UTP evoked an early peak rise in [Ca 2C ] i with maximal increases occurring at approximately 30 s, followed by a progressively decreasing level (over 6 min) to the initial, pre-stimulated level (Fig.…”