A bryostatin-sensitive protein kinase C required for nerve growth factor activity

Singh, Kuber R.; Taylor, Lori K.; Campbell, X. Z.; Fields, Alan P.; Neet, Kenneth E.

doi:10.1021/bi00168a020

Cited by 28 publications

(32 citation statements)

References 89 publications

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“…The third group is the atypical PKCs, including PKC and PKC, which are unresponsive to calcium and diacylglycerol/phorbol esters (35,36). In NGFinduced neurite outgrowth, the activation of PKC by bryostatin or by a phorbol ester such as phorbol 12-myristate 13-acetate enhances neurite outgrowth (37,38). Moreover, the PKC␦ and PKC⑀ isotypes of PKC play a role in NGF-induced neurite outgrowth (38,39), and activation of PKC⑀ is more effective in enhancing neurite outgrowth (40,41).…”

Section: Discussionmentioning

confidence: 99%

Induction of Neurite Outgrowth in PC12 Cells by α-Phenyl-N-tert-butylnitron through Activation of Protein Kinase C and the Ras-Extracellular Signal-regulated Kinase Pathway

Tsuji

Inanami

Kuwabara

2001

Journal of Biological Chemistry

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The spin trap ␣-phenyl-N-tert-butylnitron (PBN) is widely used for studies of the biological effects of free radicals. We previously reported the protective effects of PBN against ischemia-reperfusion injury in gerbil hippocampus by its activation of extracellular signalregulated kinase (ERK) and suppression of both stressactivated protein kinase and p38 mitogen-activated protein kinase. In the present study, we found that PBN induced neurite outgrowth accompanied by ERK activation in PC12 cells in a dose-dependent manner. The induction of neurite outgrowth was inhibited significantly not only by transient transfection of PC12 cells with dominant negative Ras, but also by treatment with mitogen-activated protein kinase/ERK kinase inhibitor PD98059. The activation of receptor tyrosine kinase TrkA was not involved in PBN-induced neurite outgrowth. A protein kinase C (PKC) inhibitor, GF109203X, was found to inhibit neurite outgrowth. The activation of PKC⑀ was observed after PBN stimulation. PBN-induced neurite outgrowth and ERK activation were counteracted by the thiol-based antioxidant N-acetylcysteine. From these results, it was concluded that PBN induced neurite outgrowth in PC12 cells through activation of the Ras-ERK pathway and PKC.

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Section: Discussionmentioning

confidence: 99%

Induction of Neurite Outgrowth in PC12 Cells by α-Phenyl-N-tert-butylnitron through Activation of Protein Kinase C and the Ras-Extracellular Signal-regulated Kinase Pathway

Tsuji

Inanami

Kuwabara

2001

Journal of Biological Chemistry

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“…In addition to causing PKC activation during shortterm incubations, both PMA and bryostatin have been reported to downregulate PKC expression in long-term incubations (Matthies et al, 1987;Singh et al, 1994). It is important to determine if the effects on PKC by PMA and bryostatin are due to the short-term activation or the long-term down-regulation.…”

Section: Pkc Downregulation By Pma and Bryostatinmentioning

confidence: 99%

“…In short-term incubations in PC12 cells, bryostatin activated protein kinase C (PKC) similarly to PMA (Singh et al, 1994). Bryostatin alone, or in combination with PMA does not induce neurites, and low concentrations of bryostatin in combination with NGF induced neurites similar to NGF alone (Campbell and Neet, 1995).…”

Section: Introductionmentioning

confidence: 99%

PKC activators (phorbol ester or bryostatin) stimulate outgrowth of NGF-dependent neurites in a subline of PC12 cells

Burry

1998

J. Neurosci. Res.

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Nerve growth factor (NGF) stimulation of PC12 cells activates signaling pathways leading to new protein expression and growth of neurites. In wild type PC12 cells, incubation with phorbol ester (PMA) will activate protein kinase C (PKC) leading to the expression of many proteins necessary for neurite outgrowth, but this activation of PKC alone will not stimulate growth of long neurites. Here, we show in the subline of PC12-N09, which lacks NGF-stimulated growth of long neurites, that a brief incubation with PKC activators, PMA or bryostatin 1 (bryostatin), before NGF incubation, stimulates the growth of long neurites. However, incubation in the reverse order is ineffective. A short incubation with PMA or bryostatin followed by NGF induced tyrosine phosphorylation of MAP kinase (MAPK), which is of the same duration as that induced by NGF alone. Thus, PMA preincubation did not increase the length NGF activation of MAPK. Twenty-four hr after incubation with PMA or bryostatin, PKC isoforms were downregulated but PKC isoforms delta-, and epsilon- were still present. In these cells chronically treated with either PMA or bryostatin to downregulate PKC, NGF incubation preceded by PMA preincubation still led to long neurite outgrowth. These results suggest that a PMA or bryostatin incubation followed by NGF activates PKC isoforms delta-, and epsilon-leading to outgrowth of long neurites, and that the PMA signaling is independent of the MAPK pathway.

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“…It acts similarly to phorbol esters by binding to the regulatory domain of PKC (Smith et al, 1985;Singh et al, 1994;Burry, 1998) and causing increased activity in membranes. In addition, both agents activate signaling pathways that lead to increased transcription and rapid early protein synthesis (Burry, 1998).…”

Section: Discussionmentioning

confidence: 99%

Bryostatin Enhancement of Memory inHermissenda

Kuzirian

Epstein

Gagliardi

et al. 2006

The Biological Bulletin

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Abstract. Bryostatin, a potent agonist of protein kinase C (PKC), when administered to Hermissenda was found to affect acquisition of an associative learning paradigm. Low bryostatin concentrations (0.1 to 0.5 ng/ml) enhanced memory acquisition, while concentrations higher than 1.0 ng/ml down-regulated the pathway and no recall of the associative training was exhibited. The extent of enhancement depended upon the conditioning regime used and the memory stage normally fostered by that regime. The effects of two training events (TEs) with paired conditioned and unconditioned stimuli, which standardly evoked only short-term memory (STM) lasting 7 min, were-when bryostatin was added concurrently-enhanced to a long-term memory (LTM) that lasted about 20 h. The effects of both 4-and 6-paired TEs (which by themselves did not generate LTM), were also enhanced by bryostatin to induce a consolidated memory (CM) that lasted at least 5 days. The standard positive 9-TE regime typically produced a CM lasting at least 6 days. Low concentrations of bryostatin (Ͻ0.5 ng/ml) elicited no demonstrable enhancement of CM from 9-TEs. However, animals exposed to bryostatin concentrations higher than 1.0 ng/ml exhibited no behavioral learning.Sharp-electrode intracellular recordings of type-B photoreceptors in the eyes from animals conditioned in vivo with bryostatin revealed changes in input resistance and an enhanced long-lasting depolarization (LLD) in response to light. Likewise, quantitative immunocytochemical measurements using an antibody specific for the PKC-activated Ca 2ϩ /GTP-binding protein calexcitin showed enhanced antibody labeling with bryostatin.Animals exposed to the PKC inhibitor bisindolylmaleimide-XI (Ro-32-0432) administered by immersion prior to 9-TE conditioning showed no training-induced changes with or without bryostatin exposure. However, if animals received bryostatin before Ro-32, the enhanced acquisition and demonstrated recall still occurred. Therefore, pathways responsible for the enhancement effects induced by bryostatin were putatively mediated by PKC.Overall, the data indicated that PKC activation occurred and calexcitin levels were raised during the acquisition phases of associative conditioning and memory initiation, and subsequently returned to baseline levels within 24 and 48 h, respectively. Therefore, the protracted recall measured by the testing regime used was probably due to bryostatininduced changes during the acquisition and facilitated storage of memory, and not necessarily to enhanced recall of the stored memory when tested many days after training.

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A bryostatin-sensitive protein kinase C required for nerve growth factor activity

Cited by 28 publications

References 89 publications

Induction of Neurite Outgrowth in PC12 Cells by α-Phenyl-N-tert-butylnitron through Activation of Protein Kinase C and the Ras-Extracellular Signal-regulated Kinase Pathway

Induction of Neurite Outgrowth in PC12 Cells by α-Phenyl-N-tert-butylnitron through Activation of Protein Kinase C and the Ras-Extracellular Signal-regulated Kinase Pathway

PKC activators (phorbol ester or bryostatin) stimulate outgrowth of NGF-dependent neurites in a subline of PC12 cells

Bryostatin Enhancement of Memory inHermissenda

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