Diverse actions of ouabain and its aglycone ouabagenin in renal cells.

The cellular actions of ouabain are complex and involve different pathways, depending on the cell type and experimental conditions. Several studies have reported that Madin-Darby canine kidney (MDCK) cellular sensitivity to ouabain is not related to Na-K-ATPase inhibition, and others showed that some cell types, such as Ma104, are resistant to ouabain toxicity albeit their Na-K-ATPase isoforms possess high affinity for this glycoside. We describe here that the effects of ouabain and ouabagenin also diverge in MDCK and Ma104 cells, being MDCK cells more resistant to ouabagenin, while Ma104 cells are resistant to both molecules.

Vanadate-induced cell death is dissociated from H2O2 generation.

Vanadium is an environmentally toxic metal with peculiar and sometimes contradictory cellular effects. It is insulin-mimetic, it can either stimulate cell growth or induce cell death, and it has both mutagenic and antineoplastic properties. However, the mechanisms involved in those effects are poorly understood.

Modulation of multidrug resistance protein (MRP1/ABCC1) expression: a novel physiological role for ouabain.

Besides being a (Na(+),K(+))-ATPase inhibitor, high doses of the hormone ouabain have also been reported to modulate both the expression and activity of proteins belonging to the ATP binding cassette family of transporters, such as ABCC7 (CFTR), ABCB1 (P-glycoprotein), and ABCC1 (MRP1). Although these proteins are present in the kidney, only ABCB1 has a putative physiological role in this organ, secreting endobiotics and xenobiotics. In the present work, we studied the relationship between ouabain and ABCC1 expression and function, aiming to establish a physiological role for ouabain.

Expression and activity of multidrug resistance protein 1 in a murine thymoma cell line.

Multidrug resistance proteins [MRPs and P-glycoprotein (Pgp)] are members of the family of ATP-binding cassette (ABC) transport proteins, originally described as being involved in the resistance against anti-cancer agents in tumour cells. These proteins act as ATP-dependent efflux pumps and have now been described in normal cells where they exert physiological roles. The aim of this work was to investigate the expression and activity of MRP and Pgp in the thymoma cell line, EL4.