Activation of multiple signaling pathways by terminal complement complexes involved in myocellular sodium homeostasis.
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 degrees 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.
Department of Traumatology and Acute Critical Medicine, University of Miyazaki, Miyazaki 889-1692, Japan. okamotok@med.miyazaki-u.ac.jp
Ken
K
Okamoto
Weiyang
W
Wang
Danny O
DO
Jacobs
Chikanori
C
Terai
D000818:Animals; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000502:physiology*; D006023:Glycoproteins / Q000502:physiology*; D006487:Hemostasis / Q000502:physiology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D032342:Muscle Cells / Q000201:enzymology / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D015054:Zymosan / Q000494:pharmacology
D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; C047610:SC5b-9 protein complex; D003165:Complement System Proteins; D015054:Zymosan; D012964:Sodium; D007770:L-Lactate Dehydrogenase; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D011188:Potassium