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Effects of extracellular Ca2+ and HCO3- on epidermal growth factor-induced DNA synthesis in cultured rat hepatocytes.

Abstract：

BACKGROUND/AIMS:The elevation of cytosolic free calcium concentration ([Ca2+]i) and intracellular pH mediate the growth factor-initiated proliferation of many cells, but it is not known if they trigger mitosis in resting hepatocytes. The maintenance of [Ca2+]i and intracellular pH depends partly on extracellular calcium concentration ([Ca2+]e) and extracellular bicarbonate concentration ([HCO3-]e). Therefore, the effects of [Ca2+]e and [HCO3-]e on hepatocyte proliferation were examined. METHODS:Epidermal growth factor induced proliferation in primary cultures of rat hepatocytes. [3H]thymidine incorporation into DNA and nuclear labeling indices were measured. RESULTS:Between 0.2 and 0.9 mmol/L of [Ca2+]e, the proliferative response to epidermal growth factor increased, and total hepatocellular Ca2+ content was increased. Increasing [HCO3-]e also stimulated DNA synthesis in a concentration-dependent manner, maximal at 35 mmol/L. Using optimal [Ca2+]e (0.9 mmol/L) and [HCO3-]e (35 mmol/L), a synergistic stimulation of hepatocellular DNA synthesis was shown. Voltage-dependent Ca2+ channel blockers failed to inhibit hepatocyte proliferation when administered in concentrations that inhibit proliferation in other cell types. CONCLUSIONS:[Ca2+]e and [HCO3-]e are both essential for hepatocyte proliferation, and their effects are synergistic. The entry of extracellular Ca2+ is critical for epidermal growth factor-induced DNA synthesis in hepatocytes, but this is not mediated by voltage-dependent Ca2+ channels.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Zhang BH,Farrell GC

doi

10.1016/0016-5085(95)90077-2

subject

Has Abstract

pub_date

1995-02-01 00:00:00

pages

477-86

issue

2

eissn

0016-5085

issn

1528-0012

pii

0016-5085(95)90077-2

journal_volume

108

pub_type

杂志文章

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