Effects of serum on calcium mobilization in the submandibular cell line A253.
The effects of serum on inositol 1,4,5-trisphosphate (IP3) formation and Ca2+ mobilization in the human submandibular cell line A253 were studied. Exposure of A253 cells to fetal bovine serum (FBS) elicited a 3.3-fold increase in IP3 formation and a concentration-dependent transient increase in cytosolic free Ca2+ concentration ([Ca2+]i), which was similar in Ca2+-containing and Ca2+-free media. Newborn bovine serum (NBS), but not bovine serum albumin (BSA), induced a similar response. The Ca2+ release triggered by FBS was significantly (88%) reduced by the phospholipase C inhibitor U73122, indicating that Ca2+ release induced by FBS is through the PLC pathway. Pretreatment with the tyrosine kinase inhibitor genistein abolished the FBS- and NBS-induced Ca2+ release, suggesting that tyrosine kinase plays an important role in mediating the Ca2+ release. Pre-exposure to ATP or thapsigargin (TG) significantly reduced the FBS-induced [Ca2+]i increase, indicating that Ca2+ release caused by FBS is from the TG- or ATP-sensitive Ca2+ store. While FBS exposure elicited a large Ca2+ release, it reduced Ca2+ influx. Furthermore, FBS significantly inhibited the Ca2+ influx activated by the depletion of intracellular stores by ATP or TG. These results suggest that (1) serum elicits Ca2+ release from ATP- and TG-sensitive stores, which is mediated by IP3; (2) the serum-induced Ca2+ release may be modulated by a tyrosine kinase-associated process; and (3) serum strongly inhibits Ca2+ influxes including the store depletion-activated Ca2+ influx.
Sun
X
X
Department of Pediatrics, University of Texas Health Science Center at San Antonio, 78284, USA.
Mörk
A C
AC
Helmke
R J
RJ
Martinez
J R
JR
Zhang
G H
GH
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002417:Cattle; D005312:Fetal Blood / Q000502:physiology*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D013365:Submandibular Gland Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism
D010738:Type C Phospholipases; D002118:Calcium