Calbindin-D28k in the Brain Influences the Expression of Cellular Prion Protein

The phenotypes of calbindin-D9k- (CaBP-9k-) knockout (KO), calbindin-D28k- (CaBP-28k-) KO, and CaBP-9k/28k-KO mice are similar to those of wild-type (WT) mice due to the compensatory action of other calcium transport proteins. In this study, we investigated the expression of cellular prion protein (PrP(C)) in the brains of CaBP-9k-, CaBP-28k-, and CaBP-9k/28k-KO mice. PrP(C) expression was significantly upregulated in the brain of all three strains. Levels of phospho-Akt (Ser473) and phospho-Bad (Ser136) were significantly elevated, but those of phospho-ERK and phospho-Bad (Ser155 and 112) were significantly reduced in the brains of CaBP-9k-, CaBP-28k-, and CaBP-9k/28k-KO mice. The expressions of the Bcl-2, p53, Bax, Cu/Zn-SOD, and Mn-SOD proteins were decreased in the brains of all KO mice. Expression of the endoplasmic reticulum marker protein BiP/GRP78 was decreased, and that of the CHOP protein was increased in the brains of those KO mice. To identify the roles of CaBP-28k, we transfected PC12 cells with siRNA for CaBP-28k and found increased expression of the PrP(C) protein compared to the levels in control cells. These results suggest that CaBP-28k expression may regulate PrP(C) protein expression and these mice may be vulnerable to the influence of prion disease.