Takahashi Kazuhiro, Ohba Koji, Tajima Kazuki, Nishijima Tsuguo, Sakurai Shigeru
Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan.
Division of Behavioral Sleep Medicine, Iwate Medical University School of Medicine, Morioka, Iwate 020-0850, Japan.
Int J Mol Sci. 2017 Jun 20;18(6):1313. doi: 10.3390/ijms18061313.
(Pro)renin receptor ((P)RR) is a multi-functional molecule that is related to both the renin-angiotensin system (RAS) and vacuolar H⁺-ATPase (v-ATPase), an ATP-dependent multi-subunit proton pump. Soluble (P)RR (s(P)RR), which consists of the extracellular domain of (P)RR, is present in blood and urine. Elevated plasma s(P)RR concentrations are reported in patients with chronic kidney disease and pregnant women with hypertension or diabetes mellitus. In addition, we have shown that plasma s(P)RR concentrations are elevated in patients with obstructive sleep apnea syndrome (OSAS). Interestingly, the levels are elevated in parallel with the severity of OSAS, but are not related to the presence of hypertension or the status of the circulating RAS in OSAS. It is known that v-ATPase activity protects cells from endogenous oxidative stress, and loss of v-ATPase activity results in chronic oxidative stress. We hypothesize that hypoxia and subsequent oxidative stress, perhaps in the brain, may be one of the factors that elevate plasma s(P)RR levels in OSAS.
（前）肾素受体（(P)RR）是一种多功能分子，与肾素-血管紧张素系统（RAS）和液泡H⁺-ATP酶（v-ATP酶，一种依赖ATP的多亚基质子泵）均相关。可溶性（P)RR（s(P)RR）由（P)RR的细胞外结构域组成，存在于血液和尿液中。据报道，慢性肾病患者以及患有高血压或糖尿病的孕妇血浆s(P)RR浓度升高。此外，我们已经表明，阻塞性睡眠呼吸暂停综合征（OSAS）患者的血浆s(P)RR浓度升高。有趣的是，其水平与OSAS的严重程度平行升高，但与OSAS患者是否存在高血压或循环RAS状态无关。已知v-ATP酶活性可保护细胞免受内源性氧化应激，而v-ATP酶活性丧失会导致慢性氧化应激。我们推测，低氧及随后的氧化应激（可能发生在大脑中）可能是OSAS患者血浆s(P)RR水平升高的因素之一。
