Activation of multiple signaling pathways by terminal complement complexes involved in myocellular sodium homeostasis

Ken Okamoto, Weiyang Wang, Danny O. Jacobs, Chikanori Terai

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Soluble C5b-9 complexes (SC5b-9), hemolytically inactive end-products of complement activation have long been considered to be irrelevant. Recent investigations, however, have demonstrated that SC5b-9 induces numerous biological effects via a series of intracellular signal transduction events. We have previously demonstrated that SC5b-9 enriched sera increased intracellular Na+ in rat skeletal muscles. This study was purposed to determine if the protein kinase C (PKC) or mitogen-activated protein kinase (MAPK) signaling pathway mediates the effects of SC5b-9. Fast-twitch extensor digitorum longus (EDL) muscles isolated from infant rats were incubated at 30°C for 60 minutes with 10% zymosan-activated rat sera (ZARS) as a source of complement. Heat-inactivated rat sera (HIRS) were used as a control. The muscles were also incubated with ZARS or HIRS in the presence of specific inhibitors against PKC (GF109203X) or MAPK (PD98059 and SB202190). Intracellular Na+ and K+ contents were then measured. ZARS significantly increased intracellular Na+ and the Na+/K+ ratio in EDL muscles as compared to HIRS. GF109203X, PD98059 and SB202190 markedly attenuated increase in myocellular Na+ induced by ZARS, respectively. We concluded that SC5b-9 enriched sera alter myocellular Na+ homeostasis, at least in part, via the mechanisms linked to PKC and MAPK signal transduction pathways.

Original languageEnglish (US)
Pages (from-to)113-122
Number of pages10
JournalTohoku Journal of Experimental Medicine
Volume202
Issue number2
DOIs
StatePublished - Feb 2004
Externally publishedYes

Fingerprint

Complement Membrane Attack Complex
Rats
Homeostasis
Sodium
Chemical activation
Zymosan
Serum
Muscle
Mitogen-Activated Protein Kinases
Protein Kinase C
Signal transduction
Hot Temperature
Muscles
Signal Transduction
Complement Activation
Skeletal Muscle
SC5b-9 protein complex

Keywords

  • C5b-9 complexes
  • Mitogen-activated protein kinase
  • Protein kinase C
  • Skeletal muscle
  • Sodium and potassium transport

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Activation of multiple signaling pathways by terminal complement complexes involved in myocellular sodium homeostasis. / Okamoto, Ken; Wang, Weiyang; Jacobs, Danny O.; Terai, Chikanori.

In: Tohoku Journal of Experimental Medicine, Vol. 202, No. 2, 02.2004, p. 113-122.

Research output: Contribution to journalArticle

Okamoto, Ken ; Wang, Weiyang ; Jacobs, Danny O. ; Terai, Chikanori. / Activation of multiple signaling pathways by terminal complement complexes involved in myocellular sodium homeostasis. In: Tohoku Journal of Experimental Medicine. 2004 ; Vol. 202, No. 2. pp. 113-122.
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