Na(+)/K(+)-ATPase Alpha 2 Isoform Elicits Rac1-Dependent Oxidative Stress and TLR4-Induced Inflammation in the Hypothalamic Paraventricular Nucleus in High Salt-Induced Hypertension.
Na(+)/K(+)-ATPase Alpha 2 Isoform Elicits Rac1-Dependent Oxidative Stress and TLR4-Induced Inflammation in the Hypothalamic Paraventricular Nucleus in High Salt-Induced Hypertension.
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Na /K -ATPase Alpha 2 同工型在高盐诱发的高血压中引发 Rac1 依赖性氧化应激和 TLR4 诱发的下丘脑室旁核炎症
DOI：
10.3390/antiox11020288
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发表时间：
2022-01-31
期刊：
影响因子：
--
通讯作者：
Kang YM
中科院分区：
文献类型：
--
作者：
Su Q;Yu XJ;Wang XM;Peng B;Bai J;Li HB;Li Y;Xia WJ;Fu LY;Liu KL;Liu JJ;Kang YM
大量研究表明，高盐饮食抑制脑Na+/K+-ATP酶（NKA）活性，并影响室旁核（PVN）的氧化应激和炎症。此外，Na+/K+-ATP酶α 2亚型（NKA α2）可能是脑内的靶点，参与盐依赖性高血压的发生。因此，我们假设NKA α2在盐诱导的高血压背景下调节PVN中的氧化应激和炎症。第一部分：我们在高盐组（8%NaCl）和正常盐组（0.3%NaCl）中评估了NKA亚基（NKA α1、NKA α2和NKA α3）、Na+/K+-ATP酶活性、氧化应激和炎症。第二部分：将NKA α2短发夹状RNA（shRNA）双侧微量注射入盐诱导的高血压大鼠室旁核（PVN），以敲低NKA α2，探讨NKA α2是否通过调节PVN中蛋白激酶C γ（PKC γ）依赖的氧化应激和Toll样受体4（TLR 4）诱导的炎症相关下游信号通路促进高血压的发生。与正常盐饮食相比，高盐饮食增加了PVN中NKA α1和NKA α2的蛋白表达，但对NKA α3没有影响。高盐组室旁核Na+/K+-ATP酶活性和ADP/ATP比值降低，而NAD（P）H活性和NF-κB B活性升高。双侧室旁核微量注射NKA α2 shRNA不仅能提高Na+/K+-ATP酶活性和ADP/ATP比值，还能抑制室旁核PKC γ依赖的氧化应激和TLR 4依赖的炎症反应，从而降低盐性高血压大鼠交感神经活性。室旁核内NKA α2可增强PKC γ/Rac 1/NAD（P）H依赖的氧化应激和TLR 4/MyD 88/NF-κ B诱导的室旁核炎症反应，从而增加MAP和交感神经活性。
Numerous studies have indicated that a high salt diet inhibits brain Na+/K+-ATPase (NKA) activity, and affects oxidative stress and inflammation in the paraventricular nucleus (PVN). Furthermore, Na+/K+-ATPase alpha 2-isoform (NKA α2) may be a target in the brain, taking part in the development of salt-dependent hypertension. Therefore, we hypothesized that NKA α2 regulates oxidative stress and inflammation in the PVN in the context of salt-induced hypertension. Part I: We assessed NKA subunits (NKA α1, NKA α2, and NKA α3), Na+/K+-ATPase activity, oxidative stress, and inflammation in a high salt group (8% NaCl) and normal salt group (0.3% NaCl). Part II: NKA α2 short hairpin RNA (shRNA) was bilaterally microinjected into the PVN of salt-induced hypertensive rats to knockdown NKA α2, and we explored whether NKA α2 regulates downstream signaling pathways related to protein kinase C γ (PKC γ)-dependent oxidative stress and toll-like receptor 4 (TLR4)-induced inflammation in the PVN to promote the development of hypertension. High salt diet increased NKA α1 and NKA α2 protein expression in the PVN but had no effect on NKA α3 compared to the normal salt diet. Na+/K+-ATPase activity and ADP/ATP ratio was lower, but NAD(P)H activity and NF-κB activity in the PVN were higher after a high salt diet. Bilateral PVN microinjection of NKA α2 shRNA not only improved Na+/K+-ATPase activity and ADP/ATP ratio but also suppressed PKC γ-dependent oxidative stress and TLR4-dependent inflammation in the PVN, thus decreasing sympathetic activity in rats with salt-induced hypertension. NKA α2 in the PVN elicits PKC γ/Rac1/NAD (P)H-dependent oxidative stress and TLR4/MyD88/NF-κB-induced inflammation in the PVN, thus increasing MAP and sympathetic activity during the development of salt-induced hypertension.
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DOI：
10.3390/molecules21091172
发表时间：
2016-09-03
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Srikanthan K;Shapiro JI;Sodhi K
通讯作者：
Sodhi K
DOI：
10.1152/ajpregu.00809.2007
发表时间：
2009-05-01
影响因子：
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Van Huysse, James W.
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