engleski

CELLULAR LOCALIZATION AND SEX-RELATED PROTEIN EXPRESSION OF ORGANIC CATION TRANSPORTERS OCT1 AND OCT2 IN MOUSE KIDNEYS AND LIVER

Organic cation transporters (OCT ; family SLC22) mediate (re)absorption of various endogenous and exogenous organic cations. In rodents, Oct1/Slc22a1 and Oct2/Slc22a2 are expressed in major excretory organs including kidneys and liver. Due to absence of specific antibodies and corresponding knockout (KO) mice, cellular localization of these transporters and their sex-related protein expression in this species have not been characterized. Here we used adult wild-type (WT) and double Oct1/Oct2 KO mice of both sexes to study a) localization of Oct1 and Oct2 by immunocytochemistry in cryosections of the liver and kidneys, b) expression of these transporters by Western blotting of isolated total cell membranes (TCM), and c) sex-dependency in localization and expression of both transporters. Using specific antibodies, in WT mice the renal Oct1 and Oct2 were localized in the basolateral membrane (BLM) of proximal tubules (PT) exhibiting sex differences (malesfemales) in the staining intensity. However, Oct1 was detected in the PT S1/S2 segments, whereas Oct2 was expressed in the PT S2/S3 segments. In the liver, Oct1 was stained in the sinusoidal membrane of hepatocytes, whereas Oct2 was undetected. In TCM of WT mice, the 75-kDa Oct1 protein band was labeled in both organs, whereas the 75-kDa Oct2 protein band was labeled exclusively in kidneys. Both transporters were undetected in Oct1/Oct2 KO mice. Collectively, in the mouse kidneys, the Oct1 and Oct2 proteins are located in the BLM of specific PT segments with male-dominant expression, whereas in the mouse liver, only the sex-independent Oct1 expresssion was found in the hepatocyte sinusoidal membrane.

immunolocalization; knockout mice; organic cations; membrane transporters; sex differences; Western blotting

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