Hepatocyte growth factor disrupts cell contact and stimulates an increase in type 3 inositol triphosphate receptor expression, intracellular calcium levels, and apoptosis of rat ovarian surface epithelial cells

The present studies revealed that hepatocyte growth factor (HGF) disrupts cell contact, increases both type 3 IP₃ receptor and intracellular calcium (Ca²⁺) levels and induces apoptosis of rat ovarian surface epithelial cells (ROSE-179 cells). Type 3 IP₃ receptor was only increased in cells that lost cell contact. Disrupting cell contact by depleting extracellular calcium (Ca²⁺) also resulted in an increase in Ca²⁺]_i levels and an increase in apoptosis. These responses were prevented by the addition of 0.7 mM Ca²⁺. Actinomycin D and cyclo-heximide prevented apoptosis that resulted from Ca²⁺ removal. In situ hybridization studies revealed that type 3 IP₃ receptor was expressed at relatively low levels by ROSE-179 cells cultured with Ca²⁺ but at high levels in the absence of Ca²⁺. ROSE-179 cells cultured in Ca²⁺-free medium with type 3 IP₃ receptor antisense oligonucleotide lost cell contact but did not show an increase in either type 3 IP₃ receptor protein, Ca²⁺]_i, or apoptosis. The nonsense oligonucleotide did not alter these responses to Ca²⁺ removal. Thus, the disruption of cell contact by either HGF or Ca²⁺ depletion increases the expression of type 3 IP₃ receptor, which causes an increase in Ca²⁺]_i and the apoptotic death of ROSE-179 cells.