Role of protein kinase C beta in phorbol ester-induced c-fos gene expression in neurons of normotensive and spontaneously hypertensive rat brains.
We have previously demonstrated that pressure application of the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) onto some neurons in the anterior hypothalamic area of rats increases neural activity in vivo and that this PKC activation-induced increase of neural activity is enhanced in spontaneously hypertensive rats (SHR), an animal model for genetic hypertension. Activation of PKC increases expression of the c-fos gene, an important transcription factor and proto-oncogene thought to be a marker of neural activity. To evaluate PKC isoforms responsible for neural activation, we examined which isoforms of PKC are involved in the PKC activation-induced c-fos gene expression in neuronal cultures of Wistar rat and spontaneously hypertensive rat (SHR) brains. PMA increased c-fos gene expression in neuronal cultures of Wistar rat brain and the PMA-induced c-fos gene expression was inhibited by the PKC inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7). The PKCalpha,beta,gamma activator thymeleatoxin also increased c-fos gene expression, while the PKCdelta,epsilon activator ingenol did not affect it. In addition, the PMA-induced c-fos gene expression was inhibited by PKCbetaantisense oligonucleotides (AON) but not by PKCalpha and PKCgammaAONs. In SHR brain neuronal cultures, the PMA-induced c-fos gene expression was enhanced as compared with that of Wistar Kyoto rats (WKY), while basal c-fos gene expression was almost the same in both neuronal cultures. The enhancement of PMA-induced c-fos gene expression in SHR brain cultures was abolished by PKCbetaAON. These findings suggest that in rat brain neuronal cultures, PMA increases c-fos gene expression via activation of PKC and that PKCbetaisoforms are partly involved in the PMA-induced c-fos gene expression. In neuronal cultures of SHR brain, it appears that the PMA-induced c-fos gene expression is also enhanced via PKCbeta.
Amemiya
Takahiro
T
Department of Pharmacology, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
Kambe
Toshie
T
Fukumori
Ryuji
R
Kubo
Takao
T
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D016762:Genes, fos / Q000187:drug effects* / Q000502:physiology*; D006973:Hypertension / Q000201:enzymology*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology*; D064546:Protein Kinase C beta; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D010703:Phorbol Esters; D011493:Protein Kinase C; D064546:Protein Kinase C beta