Cell type-specific expression of the genes for the protein kinase C family: Down regulation of mRNAs for PKCα and nPKCε upon in vitro differentiation of a mouse neuroblastoma cell line Neuro 2a

Wada, Hideo; Ohno, Shigeo; Kubo, Kyoko; Taya, Choji; Tsuji, Syuichi; Yonehara, Shin; Suzuki, Koichi

doi:10.1016/0006-291x(89)91102-9

Cited by 66 publications

(40 citation statements)

References 13 publications

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“…Neurites were detected either in N and I type cells. This observation extends knowledge obtained from previous results [5,7] on the role of PKC in neuroblastoma cell differentiation and shows that specific inhibition of PKC produces neurite outgrowth of diverse human neuroblastoma cell variants. …”

Section: Introductionsupporting

confidence: 91%

The specific inhibitor of protein kinase C, 1‐(5‐isoquinolinylsulfonyl)‐2‐methylpiperazine (H7), induces morphological change and cell differentiation of human neural crest‐derived cell lineages

1990

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It has been proved that inhibition of protein kinase C by 1-(5-isoquinolinylsulfonyl)-I-methylpiperazine (H7) induces morphological differentiation in murine neuroblastoma (nb) cell. Here we report that H7 is also active on human nb cell lines. The human nb cell had originally neuroblast-like (N) or intermediate (I) morphology. N and I type are thought to represent different stages of neuroblastoma differentiation. Neurite outgrowth was observed in both N and I type morphology treating the cells with 7, 14 or 28 PM of H7. The results confirm previous observations and show that inhibition of PKC by H7 also promotes neuronal differentiation in human cell line variants.Neural differentiation; Protein kinase C; I-(5Isoquinolinylsulfonyl)-2-methylpiperazine (H7); Human neuroblastoma

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Section: Introductionsupporting

confidence: 91%

The specific inhibitor of protein kinase C, 1‐(5‐isoquinolinylsulfonyl)‐2‐methylpiperazine (H7), induces morphological change and cell differentiation of human neural crest‐derived cell lineages

1990

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“…Possibly, it is the level of total cellular PKC activity inhibition which determines whether apoptosis will occur, and the larger fraction of total non-classical PKC activity in central neurons resistant to Gö 6976 compared with Neuro-2A cells, which only express e and z PKC as novel and atypical isoforms, 85,92 is what explains this difference. Alternatively, it is possible that inhibition of novel or atypical isoforms is specifically required to trigger cortical neuronal apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Prevention of neuronal apoptosis by phorbol ester-induced activation of protein kinase C: blockade of p38 mitogen-activated protein kinase

et al. 1999

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“…It has also been reported that neurite outgrowth induced by the phorbol ester PMA in neuroblastoma cells is associated with a down-regulation of PKC (28) and that the induction of differentiation ofNeuro-2a cells in vitro by agents such as the ganglioside GM1 or 8-bromoadenosine 3',5'-cyclic monosphosphate is associated with down-regulation of the mRNA for PKC (29). These results, together with those reported in this paper, clearly demonstrate that PKC plays an essential role in the control of neural differentiation.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of protein kinase C induces differentiation in Neuro-2a cells.

Miñana

Felipo

Grisolı́a

1990

Proc. Natl. Acad. Sci. U.S.A.

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ABSTRACT1-(5-Isoquinolinylsulfonyl)-2-methylpiperazine (H7), a potent inhibitor of protein kinase C, induced neuritogenesis in Neuro-2a cells, whereas N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA 1004), which inhibits more efficiently cAMP-and cGMP-dependent protein kinases, did not. The effect, noticeable after 3 hr, was maximum (13-fold increase at 500 ,tM H7) between 1 and 3 days and was maintained over 2 months. In controls, 90% of the cells were undifferentiated, whereas after 3 hr with 500 FIM H7 only 25% of the cells remained undifferentiated. DNA synthesis decreased as the number of differentiated cells increased. Differentiation is also functional since acetylcholinesterase activity increased =7-fold after 48 hr with 500 IAM H7. Phorbol 12-myristate 13-acetate, a specific activator of protein kinase C, prevented or reversed the induction of neuritogenesis and the inhibition of DNA synthesis by H7. There is a good correlation between the level of protein kinase C and the percentage of differentiated cells. The results indicate that protein kinase C may play a key role in the control of differentiation of neural cells. Some possible clinical implications are briefly discussed.The molecular regulation of cellular growth and differentiation is one of the fundamental problems of cell biology. It was shown some years ago that addition ofgangliosides induces the differentiation of neuroblastoma cell lines with concomitant sprouting and extension of neurites (1-3). However, the underlying mechanism of ganglioside-modulated neuritogenesis remained unknown (4, 5). It has been reported by others that gangliosides are inhibitors of protein kinase C (PKC) (6-8). It therefore appeared possible that the two findings might be related and that gangliosides might stimulate neuritogenesis by inhibiting PKC. To test this hypothesis we have studied the effect of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (17), a potent inhibitor ofPKC (9, 10), on differentiation in Neuro-2a cells. We find that H7 induces neuritogenesis and that this effect is prevented and reversed by phorbol 12-myristate 13-acetate (PMA), an activator ofPKC (11). It is further shown that there is a good correlation between the level ofthe enzyme and the percentage of differentiated cells. The results indicate that PKC may play an important role in the control of differentiation of neural cells. MATERIALS AND METHODS

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Cell type-specific expression of the genes for the protein kinase C family: Down regulation of mRNAs for PKCα and nPKCε upon in vitro differentiation of a mouse neuroblastoma cell line Neuro 2a

Cited by 66 publications

References 13 publications

The specific inhibitor of protein kinase C, 1‐(5‐isoquinolinylsulfonyl)‐2‐methylpiperazine (H7), induces morphological change and cell differentiation of human neural crest‐derived cell lineages

The specific inhibitor of protein kinase C, 1‐(5‐isoquinolinylsulfonyl)‐2‐methylpiperazine (H7), induces morphological change and cell differentiation of human neural crest‐derived cell lineages

Prevention of neuronal apoptosis by phorbol ester-induced activation of protein kinase C: blockade of p38 mitogen-activated protein kinase

Inhibition of protein kinase C induces differentiation in Neuro-2a cells.

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