190 EXPRESSION OF APOPTOTIC GENES IS MEDIATED BY CALCIUM-BINDING PROTEINS, CALBINDINS, IN THE UTERUS OF CALBINDIN-D9k AND CALBINDIN-D28k KNOCKOUT MICE

Abstract

Calcium (Ca²⁺) is known to be an important regulator in apoptotic signalling. The uterine calbindins, calbindin-D9k (CaBP-9k) and calbindin-28k (CaBP-28k), are known to be involved in the regulation of myometrial activities by regulating intracellular Ca²⁺. In addition, the uterine calbindins are expressed in the mouse endometrium and are highly regulated during implantation and development. The aim of the present study was to evaluate the regulation of apoptosis in the uterus of immature CaBP-9k, CaBP-28k, and CaBP-9k/28k knockout (KO) mouse models. Our findings indicate that Bax protein levels were enhanced in the uterus of CaBP-28k and CaBP-9k/28k KO mice compared with wild-type mice, and no difference was observed in Bcl-2 protein expression. In addition, the levels of caspase 3, 6, and 7 protein were induced in both CaBP-28k and CaBP-9k/28k KO mice compared with wild-type mice. These results suggest that the absence of calbindins may induce an increase in apoptotic signalling. In addition, we investigated the expression of the endoplasmic reticulum stress genes by Western blot analysis in calbindin KO mice. These results showed that CHOP and BiP proteins were increased in CaBP-28k and CaBP-9k/28k KO mice compared with wild-type mice, and no difference was observed in the expression of PDI and IRE1α proteins. It is of interest that the expression of CaBP-28k may block up-regulation of apoptosis-related genes. In summary, this study implies that CaBP-28k may decrease apoptosis-related gene expression in the uterine tissue of immature mice.