| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
Human hypertension is a multifactorial disease which is complicated by genetic and environmental factors. Excessive dietary sodium intake is an important factor in hypertension ; however, the molecular basis of the salt sensitivity in hypertension is not yet fully understood (Campese, 1994). Recently, we isolated a novel rat cDNA named salt-tolerant protein (S7F), using functional complementation to improve the growth of the yeast S.cervisiae HAL1- deficient strain under high salt conditions (Tsuji et al. 1996). HAL1 confers salt tolerance by modulating cation transport systems and could interact with transport systems which determine intracellular K^+ homeostasis (Gaxiola et al. 1992). The STPgene is expressed in several different rat tissues as a single transcript of 2.1 Kb and is induced by high-salt loading. STP may play an important role in the increase in blood pressure associated with excess salt intake. Immunohistochemical examination revealed that STP is localized mainly in the proximal tubules of rat kidney.
To determine the physiological function of this gene, we examined whether intracellular cation content is affected by STP. The intracellular [Na^+]/[K^+] ratio in STP-transfected cells was higher than that in control cells, suggesting that STP somehow affects intracellular cation homeostasis. This protein might increase sodium influx and/or decrease sodium efflux by modulating Na^+, K^+ -ATPase, Na^+, K^+ -cotransport and other membranous ion- transport systems. The STP gene may increase renal sodium reabsorption in proximal tubules, and thus be an important determinant of hypertension associated with excess salt intake (Tsuji et al. 1998). In the present study we have isolated and sequenced the cDNA encoding HSTPand mapped the gene to human chromosome 19 by FISH.
STP interacts with Cdc42 and plays a role in the regulation of the actin cytoskeleton.
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