The mechanism of blood pressure regulation by high potassium diet in the kidney / 生理学报

Hypertension is one of the strongest risk factors for cardiovascular diseases, cerebral stroke, and kidney failure. Lifestyle and nutrition are important factors that modulate blood pressure. Hypertension can be controlled by increasing physical activity, decreasing alcohol and sodium intake, and stopping tobacco smoking. Chronic kidney disease patients often have increased blood pressure, which indicates that kidney is one of the major organs responsible for blood pressure homeostasis. The decrease of renal sodium reabsorption and increase of diuresis induced by high potassium intake is critical for the blood pressure reduction. The beneficial effect of a high potassium diet on hypertension could be explained by decreased salt reabsorption by sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT). In DCT cells, NCC activity is controlled by with-no-lysine kinases (WNKs) and its down-stream target kinases, Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress-responsive 1 (OSR1). The kinase activity of WNKs is inhibited by intracellular chloride ([Cl-]i) and WNK4 is known to be the major WNK positively regulating NCC. Based on our previous studies, high potassium intake reduces the basolateral potassium conductance, decreases the negativity of DCT basolateral membrane (depolarization), and increases [Cl-]i. High [Cl-]i inhibits WNK4-SPAK/OSR1 pathway, and thereby decreases NCC phosphorylation. In this review, we discuss the role of DCT in the blood pressure regulation by dietary potassium intake, which is the mechanism that has been best dissected so far.

Recent progress of hypoxia inducible factor-prolyl hydroxylase domain containing enzymes inhibitors / 国际药学研究杂志

Hypoxia inducible factor (HIF) is a transcription factor widely existing in mammalian and human cells. Prolyl hydroxylase domain-containing enzymes (PHD) is the rate-limiting enzyme of HIF degradation which can hydroxylize proline residues of HIF. Therefore, HIF-PHD inhibitors (PHI) may participate in regulating the expression of gene mediated by HIF, and play important biological roles, for example, pharmacological stabilization of HIF protein with PHD inhibitors can increase the expression of erythropoietin. In this review, PHI are mainly classified according to their mechanism, and the potential indications and the latest clinical research progress of a few small molecular PHI are surveyed.

P70S6K is involved in the inhibition of testosterone production in TM3 mouse Leydig cells overexpressing Cox7a2 / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of Cox7a2 on the LH-induced testosterone production and the involved autophagy regulating signals in TM3 mouse Leydig cells.</p><p><b>METHODS</b>The Cox7a2-pEYFP-N1 fluorescent protein vector was constructed and transfected into TM3 mouse Leydig cells. The level of testosterone was determined by ELISA, and the effects of Cox7a2 on the expression of the steroidogenic acute regulatory protein (StAR) and the phosphorylation of the autophagy regulatory factor P70S6K were detected by Western blot.</p><p><b>RESULTS</b>LH stimulation increased the StAR protein expression and testosterone production, while Cox7a2 decreased P70S6K phosphorylation, reduced StAR expression and consequently inhibited LH-induced testosterone biosynthesis in the TM3 Leydig cells.</p><p><b>CONCLUSION</b>Cox7a2 inhibits testosterone production by decreasing the StAR protein expression, which might be at least in part related with the activation of autophagy in TM3 mouse Leydig cells.</p>