Inhibition of protein kinase C induces differentiation of neuroblastoma cells

Miñana, María‐Dolores; Felipo, Vicente; Grisolı́a, Santiago

doi:10.1016/0014-5793(89)81087-7

Cited by 37 publications

(9 citation statements)

References 13 publications

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“…In fact, inhibition of DNA synthesis in neuroblastoma cells causes a rapid depletion of PKC (Minana et al, 1989), which is in agreement with our observation of neurite outgrowth following PKC inhibition.…”

Section: Discussionsupporting

confidence: 89%

“…The cyclic AMP-dependent protein kinase, protein kinase A (PKA) and the Ca2 + , phospholipid-dependent protein kinase, protein kinase C (PKC), are highly expressed in nervous tissue (for review, see Nestler and Greengard, 1984) and function in neuronal differentiation, neuritogenesis, cytoskeletal protein phosphorylation, long-term potentiation, and neuronal circuit cytoarchitecture (Aletta et al, 1989;Clark and Lee, 1991;Felipo et al, 1990;Hammerling et al, 1987;Heikkila et al, 1989;. , 1987; Leli et al, 1991;Mattson, 1990;Minana et a]., 1989;Olds et al, 1989;Sihag et al, 1988). Furthermore, neurite extention by many neuronal cell lines following treatment with the cAMP analogue dbcAMP (Abraham et al, 1991;Prasad and Hsie, 1971;Shea et al, 1985) is likely to be due to PKA activation, since dbcAMP, like CAMP, functions solely through PKA activation (Adelstein, 1982;Glass and Krebs, 1980).…”

Section: Introductionmentioning

confidence: 99%

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Opposing influences of protein kinase activities on neurite outgrowth in human neuroblastoma cells: Initiation by kinase A and restriction by kinase C

Shea

Beermann

Leli

et al. 1992

J of Neuroscience Research

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The respective roles of cAMP-dependent protein kinase (protein kinase A [PKA]) and protein kinase C (PKC) in the early stages of neurite outgrowth were examined in SH-SY-5Y human neuroblastoma cells. Forskolin or dbcAMP, agents that increase intracellular cAMP levels, and intracellular delivery of PKA catalytic subunit induced neurite outgrowth. The PKA inhibitor, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA 1004), prevented the increases, and decreased further the percentage of cells possessing short, filopodia-like neurites in the absence of inducers. In contrast to effects on PKA activation, PKC activation by 12-0-tetradecanoylphorbol-13-acetate (TPA) reduced the percentage of filopodia-like neurites elaborated by otherwise untreated cells, and prevented neurite outgrowth induced by PKA activators. PKC inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7), staurosporine, and sphingosine induced neurite outgrowth. Neurites induced by PKA activation contained higher levels of tubulin immunoreactivity than those induced by PKC inhibition. Furthermore, PKA-induced neurites rapidly retracted in the presence of colchicine, while those elaborated following PKC inhibition were more resistant. These data suggest that neurites elaborated in response to PKA activation are dependent upon microtubule polymerization, and that neurite induction following PKC inhibition is mediated by a different mechanism. PKA activators and PKC inhibitors exerted additive effects on neurite outgrowth, suggesting that the distinct pathways regulated by these two kinases function cooperatively during neuritogenesis.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Opposing influences of protein kinase activities on neurite outgrowth in human neuroblastoma cells: Initiation by kinase A and restriction by kinase C

Shea

Beermann

Leli

et al. 1992

J of Neuroscience Research

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“…Protein kinase C plays a pivotal role in neuronal differentiation and homeostasis. Inhibition of protein kinase C (PKC) promotes neurite outgrowth, whereas activation restricts it (Minana et al, 1989;Tsuda et al, 1989;Heikkila et al, 1991;Shea and Beermann, 1991;Ono et al, 1991Ono et al, , 1993Leli et al, 1992a,b;Shea et al, 1992a). Two modes of PKC activation have been described.…”

Section: Introductionmentioning

confidence: 99%

Hyperphosphorylation of TAU and filopodial retraction following microinjection of protein kinase C catalytic subunits

Cressman

Shea

1995

J of Neuroscience Research

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Limited proteolysis of protein kinase C (PKC) by calcium-activated proteolysis cleaves the regulatory and catalytic subunits of PKC, generating a free, constitutively activated kinase ("PKM") that, unlike the intact parent enzyme, is not calcium-dependent, and is not restricted to the plasma membrane. These latter properties leave open the possibility that PKM may have access to, and may therefore phosphorylate, substrates normally unavailable to intact PKC. We examined the potential involvement of such aberrant phosphorylation in certain aspects of the neurodegeneration accompanying Alzheimer's disease by microinjecting PKC and PKM, along with a rhodamine-conjugated dextran tracer, into undifferentiated NB2a/d1 mouse neuroblastoma cells. After 4 hr, cultures were fixed and processed for immunofluorescence with monoclonal antibodies (PHF-1, ALZ-50, Tau-1, AT8) directed against tau in various phosphorylation states followed by fluorescein-conjugated secondary antibodies. Microinjected cells were localized via co-injected rhodamine-conjugated dextran tracer under rhodamine illumination, after which antibody immunoreactivity was examined under fluorescein illumination. Microdensitometric analyses indicated that microinjection of PKC did not increase basal immunofluorescent intensities of the antibodies; by contrast, microinjection of PKM induced three- and twofold increases in PHF-1 and ALZ-50 levels, respectively. By contrast, no significant alteration was observed in AT8 and Tau-1 immunofluorescence following either PKC or PKM microinjection. Whereas undifferentiated NB2a/d1 cells typically elaborate short, filopodia-like neurites, phase-contrast microscopy revealed the absence of filopodia or neurites on PKM-injected cells, while a similar percentage of PKC-injected cells. Cell-free analyses confirmed the ability of PKC, in the presence of necessary co-factors, and PKM to increase PHF-1 and ALZ-50 immunoreactivity; no change was observed in AT8 or Tau-1 immunoreactivity. These findings underscore the possibility that an abnormal amplification in limited PKC proteolysis to generate PKM could, under certain pathological conditions, contribute to neuronal degeneration.

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“…This suggests that a decline in PKC and/or continuous activation of PKA is also involved in neurite formation, particularly in neurite maintenance. It has been reported that a PKC inhibitor, l-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), induces neurite elongation in mouse neuroblastoma Neuro 2a cells (Minana et al, 1989), N18TG-2 cells (Tsuda et al, 1989), or human neuroblastoma cells (Parodi et al, 1990). In human neuroblastoma LA-N-5 cells, dephosphorylation of 80-kDa PKC substrate by a decline in PKC activity also correlates to neurite extension (Girard and Kuo, 1990).…”

Section: Discussionmentioning

confidence: 99%

Involvement of Growth‐Associated Protein‐43 with Irreversible Neurite Outgrowth by Dibutyryl Cyclic AMP and Phorbol Ester in NG108–15 Cells

Kumagai

Tohda

Isobe

et al. 1992

Journal of Neurochemistry

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Simultaneous treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) and dibutyryl cyclic AMP (diBu-cAMP) for 72 h induced neurites in NG108-15 cells significantly longer than treatment with each alone. Treatment for 72 h with both drugs induced irreversible neurite extension and a decline in protein kinase C activity, although neurites extended by diBu-cAMP alone disappeared after the withdrawal of the drug. The expression of growth-associated protein-43 (GAP-43) mRNA was also observed by a combined application of TPA and diBu-cAMP. The increased level of GAP-43 mRNA induced by treatment with both drugs for 72 h was maintained at least 24 h after withdrawal of the drugs. In cells transfected with GAP-43 cDNA, neurites induced by treatment with diBu-cAMP alone for 72 h were maintained at least 48 h after removal of the drugs. These results suggest that GAP-43 could be involved in the maintenance of elongated neurites and that a decline in protein kinase C activity may be involved in the accumulation of GAP-43.

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Inhibition of protein kinase C induces differentiation of neuroblastoma cells

Cited by 37 publications

References 13 publications

Opposing influences of protein kinase activities on neurite outgrowth in human neuroblastoma cells: Initiation by kinase A and restriction by kinase C

Opposing influences of protein kinase activities on neurite outgrowth in human neuroblastoma cells: Initiation by kinase A and restriction by kinase C

Hyperphosphorylation of TAU and filopodial retraction following microinjection of protein kinase C catalytic subunits

Involvement of Growth‐Associated Protein‐43 with Irreversible Neurite Outgrowth by Dibutyryl Cyclic AMP and Phorbol Ester in NG108–15 Cells

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