engleski

Sodium-dicarboxylate co-transporter NaDC-3 in the mammalian kidney ; species and sex differences

NaDC-3 (SLC13A3) generates an in-to-out gradient of dicarboxylates, which is a driving force for several renal exchangers that mediate secretion of endogenous and xenobiotic organic anions (OA). NaDC-3 has been cloned from different species, characterized biochemically and functionally, and localized to the proximal tubule (PT) basolateral membrane (BLM). However, its detailed localization along the nephron, and regulation of its expression in vivo, has been poorly studied. We have raised a novel polyclonal antibody against the synthetic peptide specific for human NaDC-3 (Ab), and characterized the expression and distribution of this transporter in male (M) and female (F) human kidneys (HK) by immunocytochemistry (IC) in tissue cryosections and by immunoblotting of isolated total cell membranes (TCM). The Ab also reacted with pig (PK) and rat (RK) kidneys. Sex differences (SD) and the role of sex hormones were studied in more details in intact, gonadectomized, and testosterone (T)-, estradiol (E)-, or progesterone (P)-treated castrated rats. In the HK, the Ab stained exclusively the BLM of PT, whereas in TCM from various tissue zones, it labelled 3 peptide-blockable protein bands (43, 60, & 80 kDa), possibly representing the degradation product, nonglycosylated, and glycosylated proteins, respectively. The band density and IC staining showed no SD. Similar pattern of protein bands, without SD, was also observed in the PK. However, in the RK, the Ab stained strongly the BLM and intracellular organelles in PT and collecting ducts, and weakly the apical domain of macula densa and distal tubules. In the RK cortex, the density of protein bands (43, 60, & 78 kDa), and the intensity of IC staining, were: a) stronger in M, b) unaffected by castration, c) upregulated by ovariectomy, and d) inhibited weakly by T- and strongly by E- and P-treatment of castrates. The data indicate the presence of species differences in the abundance, distribution, and sex hormone-driven expression of renal NaDC-3.

gender differences; human; nephron; pig; rat; organic anions

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