Homocysteine inhibits store-mediated calcium entry in human endothelial cells: evidence for involvement of membrane potential and actin cytoskeleton.
The role of homocysteine for store-operated calcium influx was investigated in human umbilical cord endothelial cell line. Homocysteine significantly decreased thapsigargin-evoked Ca2+ entry, membrane hyperpolarization and actin polymerization. GSH and DTT prevented homocysteine-induced inhibition of thapsigargin-evoked Ca2+ entry, membrane hyperpolarization and actin polymerization; while GSSG had the opposite effect. Homocysteine blocked large conductance Ca2+-activated K+ (BK(Ca)) channels in a concentration-dependent manner and related to the redox status of the endothelial cells. BK(Ca) channels opener NS1619 reversed thapsigargin-evoked Ca2+ entry, membrane hyperpolarization and actin polymerization; BK(Ca) channels inhibitor iberiotoxin had the opposite effect. The findings suggest that homocysteine is involved in store-regulated Ca2+ entry through membrane potential-dependent and actin cytoskeleton-dependent mechanisms, redox status of homocysteine and BK(Ca) channels may play a regulatory role in it.
Zhang
Hong-Sheng
HS
Center for System Biology, Institute of Biophysics, Acadenia Sinica, Chaoyang District, Beijing, PR China.
Xiao
Jun-Hua
JH
Cao
En-Hua
EH
Qin
Jin-Fen
JF
D008841:Actin Cytoskeleton / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D003599:Cytoskeleton / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005978:Glutathione / Q000494:pharmacology; D019803:Glutathione Disulfide / Q000494:pharmacology; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors*; D019284:Thapsigargin / Q000494:pharmacology
D024681:Potassium Channels, Calcium-Activated; D006710:Homocysteine; D019284:Thapsigargin; D005978:Glutathione; D002118:Calcium; D004229:Dithiothreitol; D019803:Glutathione Disulfide