Regulation of Renal Na+/HCO 3 − Cotransporter Stimulation by CO 2 : Role of Phosphorylation, Exocytosis and Protein Synthesis
The Journal of membrane biology(2004)
摘要
The sodium bicarbonate cotransporter (NBC1) mediates bicarbonate reabsorption in the renal proximal tubule. NBC1 activity is stimulated by 10% CO 2 , however, the mechanism is poorly understood. Here, we examined the mechanism of NBC1 regulation by 10% CO 2 using an immortalized human proximal tubule cell line (HK2). In cells exposed to 10% CO 2 , the cotransporter activity (measured as ΔpH/min) increased within minutes and this increase was maintained for 6 to 24 h. Early NBC1 stimulation was accompanied by increased NBC1 phosphorylation. Basolateral membrane NBC1 protein increased by 30 min and reached a maximum at 6 h. Increased NBC activity at 6 h was accounted for by increased NBC exocytosis to the basolateral membrane and not by decreased endocytosis. Latruncullin B (an actin cytoskeleton inhibitor) did not prevent CO 2 -induced stimulation, while nocodazole (a microtubule-disrupting agent) abrogated the stimulatory effect of 10% CO 2 . A significant increase in NBC1 mRNA expression level was observed at 6 h and maintained for 24 h. Total NBC1 protein increased at 12 to 24 h with 10% CO 2 incubation and this effect was blocked by cycloheximide. In summary, the present study demonstrates that early activation of NBC1 activity by 10% CO 2 was mediated by NBC1 phosphorylation. The stimulation of cotransporter activity observed at 6 h was due to exocytosis, while the late effect starting from 12 h was accounted for by increased protein synthesis.
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关键词
Na + /HCO 3 − cotransporter
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