CA2+ INFLUX VIA T-TYPE CHANNELS MODULATES PDGF-INDUCED REPLICATION OF MOUSE FIBROBLASTS

被引:87
作者
WANG, Z [1 ]
ESTACION, M [1 ]
MORDAN, LJ [1 ]
机构
[1] UNIV HAWAII MANOA, CANC RES CTR HAWAII, 1236 LAUHALA ST, HONOLULU, HI 96813 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY | 1993年 / 265卷 / 05期
关键词
VOLTAGE-GATED CALCIUM CHANNELS; CELL PROLIFERATION; NORDIHYDROGUARIARETIC ACID; PLATELET-DERIVED GROWTH FACTOR;
D O I
10.1152/ajpcell.1993.265.5.C1239
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The role of low-threshold voltage-gated calcium channels (VGCC) in modulating extracellular calcium influx and proliferation was investigated in platelet-derived growth factor (PDGF)-stimulated C3H/10T1/2 mouse fibroblasts. Previous studies demonstrated that cell cycle progression after PDGF stimulation was dependent on extracellular calcium influx producing a sustained increase in the intracellular calcium concentration. In this study, PDGF-induced calcium influx, the sustained intracellular calcium increase, and progression to S phase were inhibited by nordihydroguariaretic acid (NDGA), an inhibitor of calcium influx through VGCC. With the use of the whole cell patch-clamp technique to measure calcium currents, NDGA inhibited inward calcium current through low-threshold VGCC, the only VGCC expressed in C3H/10T1/2 fibroblasts. The inhibitory effects of NDGA on calcium influx and cell proliferation each had a mean inhibitory dose of 2-3 muM. Although NDGA also effectively inhibits cyclooxygenase and lipoxygenase, the addition of prostaglandins or leukotrienes could not reverse this inhibition nor could it be replicated by other antioxidants. These data support the hypothesis that low-threshold VGCC can mediate extracellular calcium influx on the stimulation of cell proliferation by PDGF.
引用
收藏
页码:C1239 / C1246
页数:8
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