engleski

Cadmium (Cd) inhibits vacuolar proton ATPase (V-ATPase)-mediated acidification in the rat epididymis

In normal rats, the acidic pH of the tubule fluid in the male reproductive tract (MRT) is required for the maintenance of sperm quiescence during storage. Treatment of rats with Cd leads to the alkalinization of this fluid by an unknown mechanism (Carlton et al., J. Toxicol. Environ. Health 32:49, 1991). We recently showed that a population of V-ATPase-rich cells in the epididymis (E) and vas deferens (VD) may be responsible for acidification in these segments (Breton et al., Nature Med. 2:470, 1996). Because Cd may influence the function of V-ATPase in these cells, we examined the effect of subchronic Cd intoxication on V-ATPase-rich cell morphology, and on the abundance and distribution of the 31 kDa V-ATPase subunit in cells along the E. Immunofluorescence and immunobloting data in rats treated with Cd for 14 days (2 mg Cd/kg BW/day) showed that: a) V-ATPase-positive cells regressed to a pre-pubertal phenotype, b) V-ATPase was lost from the cell apical pole and was redistributed into an intracellular compartment, c) V-ATPase abundance was diminished in isolated E plasma membranes (PM). The acute effect of Cd on V-ATPase function was also examined in vitro; Cd (0.5 mM) inhibited the bafilomycin-sensitive ATPase activity in PM by 75%, and also inhibited proton secretion in the VD by 61%, as measured using a proton-selective extracellular microelectrode. We conclude that alkalinization of the tubule fluid in the MRT of Cd-treated rats may result from the loss of V-ATPase units from the cell membrane as well as from a direct inhibition by Cd of V-ATPase function.

proton pump; cadmium; epididymis; rat

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