Expressão de proteínas envolvidas no transporte transepitelial de cálcio na próstata de ratos em envelhecimento

Abstract

Calcium is a second messenger crucial for the execution of diverse cellular functions, including cell proliferation, survival and death. Its transport across epithelia is performed in three steps through the action of proteins as the TRPV6 channel, which mediates its influx in the cells; calbindin, calcium binding protein that facilitates its diffusion through the cytoplasm and protects the cell from unintended signals; and the PMCA pump, which promotes its extrusion. Aging is a complex process marked by the occurrence of metabolic deregulations, including a disruption in Ca2+ homeostasis that increases the risk for the development of clinically relevant diseases, such as the prostate cancer. Nevertheless, the expression status of TRPV6, PMCA and calbindin in advanced age and in epithelial lesions of the prostate remains to be unravelled. Therefore, we aimed to map these proteins involved in calcium transepithelial transport in the healthy and altered prostates of Wistar rats, which develop benign, premalignant and malignant histopathological lesions similar to those of the human prostate. To this purpose, two experimental models were applied in the present study: physiological aging and hormonal induction of carcinogenesis by Testosterone + Estradiol (T+E2). Western blotting was performed in target-tissues of young rats, as well as in the ventral and lateral prostates of rats of different ages for the detection of TRPV6 and PMCA. Additionally, immunohistochemical assays were conducted for the detection of both transporters and calbindin in the ventral and lateral prostates of aging and T+E2-treated rats. TRPV6 and PMCA were expressed in higher levels by the ventral and lateral prostates, when compared to the other prostate lobes. The three target-proteins of this study had altered expression levels in epithelial lesions of the prostates, with reduced calbindin detection in the proliferative lesions PIN and cancer. PMCA was reduced in these two lesions as well, and also in squamous metaplasia, PIA and atrophy, whereas TRPV6 was overexpressed by a subset of basal cells more frequently present in squamous metaplasia, PIA and some sites of cancer. The punctually changed expression of calcium transporters in prostatic lesions commonly found upon aging, as well as the increased expression of TRPV6 by a subset of basal cells present in these lesions, are suggestive of a failure in the control of intracellular calcium availability, and reveal a possible mechanism contributing to the development of highly prevalent disorders in the senile prostate.