Biomedical Research

Multidrug resistance-associated proteins (MRPs) are efflux transporters known to transport a diverse set of substrates, such as amphipathic chemicals, organic anions and endogenous molecules. MRP2 generally performs excretory or protective roles, and is primarily expressed on the apical domain of hepatocytes. High gravitational acceleration force acting along the body axis from the head to the feet (+Gz) causes considerable strain to several organ systems. Exposure to high +Gz severely reduces blood flow to the visceral organs, including the liver. Whereas previous studies have shown the regulation of MRP2 expression in some experimental animal models, the altered expression of MRP2 associated with +Gz exposure has not yet been investigated. The aim of the present study was to examine the effect of high +Gz exposure on hepatic MRP2 expression. Using a small animal centrifuge, nineteen male Sprague-Dawley rats were exposed to +10Gz or +13Gz three times for 3 minutes each. The entire liver was obtained from each rat, and the expression levels of MRP2 were evaluated using immunohistochemistry. MRP2 expression was restricted to the canalicular membranes of hepatocytes. In the control group, MRP2 was localized in a strictly polarized fashion, yielding spider-like canalicular structures. Rats exposed to +10Gz also showed a typical, strong canalicular MRP2 staining, which resembled the control group. By contrast, in rats exposed to +13Gz, the staining was weak, fuzzy and frequently absent among the hepatocytes. This study is the first to describe +Gz exposure-induced alteration in the expression of hepatic MRP2. We observed significantly reduced MRP2 expression in the liver of rats exposed to +13Gz. These finding suggests that down-regulation of hepatic MRP2 occurs after high +Gz exposure.

Author(s): Hyun-Soo Kim, Sang Hwa Lee, Kyung Wook Kang, Youn Wha Kim
Abstract | Full-Text | PDF

Share this