Propofol induced diverse and subtype-specific translocation of PKC families

• Miyahara, Takeshi

• Adachi, Naoko

• Seki, Takahiro

• Hide, Izumi

• Tanaka, Shigeru

• Saito, Naoaki

• Irifune, Masahiro

• Sakai, Norio

Bibliographic Information

Other Title

• Cystamine-mediated inhibition of protein disulfide isomerase triggers aggregation of misfolded orexin-A in the Golgi apparatus and prevents extracellular secretion of orexin-A

Abstract

Propofol is the most commonly used anesthetic. Immunohistochemical studies have reported that propofol translocated protein kinase Cs (PKCs) in cardiomyocyte in a subtype-specific manner; however detailed features of the propofol-induced translocation of PKCs remain unknown. In this study, we performed real-time observation of propofol-induced PKC translocation in SH-SY5Y cells expressing PKCs fused with a fluorescent protein. Propofol unidirectionally translocated γPKC-GFP, a conventional PKC, and ζPKC-GFP, an atypical PKC, to the plasma membrane and nucleus, respectively, whereas the propofol-induced translocation of novel PKCs was diverse and subtype-specific among δPKC, εPKC and ηPKC. The propofol-induced translocation of εPKC-GFP was especially complicated and diverse, that is, 200 μM propofol first translocated εPKC-GFP to the perinuclear region. Thereafter, εPKC was translocated to the nucleus, followed by translocation to the plasma membrane. Analysis using a mutant εPKC in which the C1 domain was deleted demonstrated that the C1b domain of εPKC was indispensable for its translocation to the perinuclear region and plasma membrane, but not for its nuclear translocation. An in vitro kinase assay revealed that propofol increased the activities of the PKCs activities at the concentration that triggered the translocation. These results suggest that propofol could translocate PKCs to their appropriate target sites in a subtype-specific manner and concomitantly activated PKCs at these sites, contributing to its beneficial or adverse effects.

Journal

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 137 (1), 20-29, 2018-05

  Elsevier B.V.

Keywords

• Propofol
• Protein kinase C
• PKC translocation

Details

• CRID: 1050856995323574528
• NII Article ID: 120006488442
• DOI: 10.1016/j.jphs.2018.03.008
• DOI: 10.1016/j.bbrc.2017.05.118
• ISSN: 13478648
• ISSN: 13478613
• ISSN: 0006291X
• HANDLE: 20.500.14094/90004991
• Web Site: https://api.elsevier.com/content/article/PII:S1347861318300677?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S1347861318300677?httpAccept=text/plain
• Web Site: https://api.elsevier.com/content/article/PII:S0006291X17310112?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0006291X17310112?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2019074872
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN