Institute for Heart Research, Department of Biochemistry, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Physiol Res. 2011;60(6):887-97. doi: 10.33549/physiolres.932153. Epub 2011 Oct 12.
For better understanding of pathophysiological processes leading to increased retention of sodium as a consequence of hyperlipidemia, the properties of renal Na,K-ATPase, a key enzyme involved in maintaining sodium homeostasis in the organism, were studied. Enzyme kinetics of renal Na,K-ATPase were used for characterization of ATP- and Na(+)-binding sites after administration of fish oil (FO) (30 mg·day(-1)) or atorvastatin (0.5 mg·100 g(-1)·day(-1)) to healthy Wistar rats and rats with hereditary hypertriglyceridemia of both genders. Untreated healthy Wistar and also hypertriglyceridemic female rats revealed higher Na,K-ATPase activity as compared to respective untreated male groups. Hypertriglyceridemia itself was accompanied with higher Na,K-ATPase activity in both genders. Fish oil improved the enzyme affinity to ATP and Na(+), as indicated by lowered values of K(m) and K(Na) in Wistar female rats. In Wistar male rats FO deteriorated the enzyme in the vicinity of the Na(+)-binding site as revealed from the increased K(Na) value. In hypertriglyceridemic rats FO induced a significant effect only in females in the vicinity of the sodium binding sites resulting in improved affinity as documented by the lower value of K(Na). Atorvastatin aggravated the properties of Na,K-ATPase in both genders of Wistar rats. In hypertriglyceridemic rats protection of Na,K-ATPase was observed, but this effect was bound to females only. Both treatments protected renal Na,K-ATPase in a gender specific mode, resulting probably in improved extrusion of excessive intracellular sodium out of the cell affecting thus the retention of sodium in hHTG females only.
为了更好地理解导致脂质异常血症时钠潴留增加的病理生理过程,研究了肾脏 Na,K-ATP 酶的特性,该酶是维持机体钠平衡的关键酶。通过测定鱼油(FO)(30mg·天(-1))或阿托伐他汀(0.5mg·100g(-1)·天(-1))给药后健康 Wistar 大鼠和遗传性高脂血症大鼠肾脏 Na,K-ATP 酶的酶动力学,对其 ATP 和 Na(+)结合位点进行了特征描述。与各自的未处理雄性组相比,未处理的健康 Wistar 大鼠和高脂血症雌性大鼠的 Na,K-ATP 酶活性更高。高脂血症本身使两性大鼠的 Na,K-ATP 酶活性升高。鱼油改善了雌性 Wistar 大鼠的酶对 ATP 和 Na(+)的亲和力,这表现为 K(m)和 K(Na)值降低。在 Wistar 雄性大鼠中,鱼油在 Na(+)结合部位附近使酶恶化,这表现为 K(Na)值升高。FO 仅在高脂血症雌性大鼠中在钠结合部位附近引起 Na,K-ATP 酶的显著作用,从而降低 K(Na)值显示出更好的亲和力。阿托伐他汀加剧了 Wistar 大鼠两性的 Na,K-ATP 酶的性质。在高脂血症大鼠中观察到对 Na,K-ATP 酶的保护,但这种作用仅与雌性有关。两种治疗方法均以性别特异性模式保护肾脏 Na,K-ATP 酶,可能导致过量的细胞内钠从细胞中排出,从而仅影响 hHTG 雌性大鼠的钠潴留。