Functional Characterization of Human Aquaporin 9 as a Facilitative Glycerol Carrier
Functional Characterization of Human Aquaporin 9 as a Facilitative Glycerol Carrier
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DOI：
10.2133/dmpk.23.279
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发表时间：
2008-01-01
影响因子：
2.1
通讯作者：
Yuasa, Hiroaki
中科院分区：
文献类型：
--
作者：
Ohgusu, Yuriko;Ohta, Kin-ya;Yuasa, Hiroaki
利用非洲爪蟾卵母细胞表达系统研究了人水通道蛋白9（humanaquaporin 9，hAQP 9）转运甘油的机制。发现hAQP 9对甘油的特异性摄取在25 ℃下是浓度依赖性的（可饱和的），符合Michaelis-Menten动力学，最大转运速率（J（max））为0.84 pmol/min/卵母细胞，Michaelis常数（K-m）为9.2 μ M，并且是温度依赖性的，当温度从25 ℃降低到4 ℃时，减少约70%。这种对浓度和温度的依赖性是载体介导型机制的特征，而不是预期不依赖于它们的通道类型。此外，发现几种甘油相关化合物，如单乙酸甘油酯，特异性抑制hAQP 9介导的甘油摄取，表明与甘油竞争的可能性。然而，发现hAQP 9介导的甘油摄取不需要Na+。所有这些结果表明hAQP 9作为甘油的促进载体发挥作用，尽管它被认为是作为通道发挥作用。本研究中的发现为其甘油转运机制提供了新的见解，并将有助于探索hAQP 9抑制剂可能通过限制肝脏甘油摄取来降低血糖水平。
The mechanism of glycerol transport by human aquaporin 9 (hAQP9), which is a liver-specific AQP water channel and can also transport glycerol, was investigated by using the Xenopus laevis oocyte expression system. It was found that specific glycerol uptake by hAQP9 was concentration-dependent (saturable) at 25 degrees C, conforming to the Michaelis-Menten kinetics with the maximum transport rate (J(max)) of 0.84 pmol/min/oocyte and the Michaelis constant (K-m) of 9.2 mu M, and temperature-dependent, being reduced by about 70% when temperature was lowered from 25 degrees C to 4 degrees C. Such dependences on concentration and temperature are characteristic of a carrier-mediated type of mechanism rather than a channel type, which is expected not to depend on them. Furthermore, several glycerol-related compounds, such as monoacetin, were found to specifically inhibit hAQP9-mediated glycerol uptake, indicating a possibility of competition with glycerol. hAQP9-mediated glycerol uptake was, however, found not to require Na+. All these results suggest that hAQP9 functions as a facilitative carrier for glycerol, although it had been believed to function as a channel. Findings in the present study provide novel insight into its glycerol-transporting mechanism and would help exploring a possibility that hAQP9 inhibitors might help lower blood glucose level by reducing gluconeogenesis by limiting hepatic glycerol uptake.