Protein Kinase C Regulates ASIC1a Protein Expression and Channel Function via NF-kB Signaling Pathway.
Mol Neurobiol
; 57(11): 4754-4766, 2020 Nov.
Article
em En
| MEDLINE
| ID: mdl-32783140
ABSTRACT
Tissue acidosis is a common feature in many pathological conditions. Activation of acid-sensing ion channel 1a (ASIC1a) plays a key role in acidosis-mediated neurotoxicity. Protein kinase C (PKC) activity has been proved to be associated with many physiological processes and pathological conditions; however, whether PKC activation regulates ASIC1a protein expression and channel function remains ill defined. In this study, we demonstrated that treatment with phorbol 12-myristate 13-acetate (PMA, a PKC activator) for 6 h significantly increased ASIC1a protein expression and ASIC currents in NS20Y cells, a neuronal cell line, and in primary cultured mouse cortical neurons. In contrast, treatment with Calphostin C (a nonselective PKC inhibitor) for 6 h or longer decreased ASIC1a protein expression and ASIC currents. Similar to Calphostin C, PKC α and ßI inhibitor Go6976 exposure also reduced ASIC1a protein expression. The reduction in ASIC1a protein expression by PKC inhibition involves a change in ASIC1a protein degradation, which is mediated by ubiquitin-proteasome system (UPS)-dependent degradation pathway. In addition, we showed that PKC regulation of ASIC1a protein expression involves NF-κB signaling pathway. Consistent with their effects on ASIC1a protein expression and channel function, PKC inhibition protected NS20Y cells against acidosis-induced cytotoxicity, while PKC activation potentiated acidosis-induced cells injury. Together, these results indicate that ASIC1a protein expression and channel function are closely regulated by the activity of protein kinase C and its downstream signaling pathway(s).
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína Quinase C
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Transdução de Sinais
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NF-kappa B
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Canais Iônicos Sensíveis a Ácido
Limite:
Animals
Idioma:
En
Revista:
Mol Neurobiol
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China