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标题：Hydrogen peroxide (H ₂O ₂) mediated activation of mTORC2 increases intracellular Na ⁺ concentration in the renal medullary thick ascending limb of Henle
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作者：Nadezhda N. Zheleznova ; Vikash Kumar ; Theresa Kurth 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2021
卷号：11
DOI：10.1038/s41598-021-86678-1
语种：English
出版社：Springer Nature
摘要：Hydrogen peroxide (H 2O 2) production in the renal outer medulla is an important determinant of renal medullary blood flow and blood pressure (BP) salt-sensitivity in Dahl salt-sensitive (SS) rats. The mechanisms and pathways responsible for these actions are poorly understood. Recently, we have discovered that the mTOR complex 2 (mTORC2) plays a critical role in BP salt-sensitivity of SS rats by regulating Na + homeostasis. PP242, an inhibitor of mTORC1/2 pathways exhibits potent natriuretic actions and completely prevented salt-induced hypertension in SS rats. In the present study, we have found that chronic infusion of H 2O 2 into the single remaining kidney of Sprague Dawley (SD) rats (3 days) stimulated the functional marker (pAKT Ser473/AKT) of mTORC2 activity measured by Western Blot analysis. No changes in mTORC1 activity in OM were observed as determined by pS6 Ser235/236/S6. Using fluorescent microscopy and the Na + sensitive dye Sodium Green, we have shown that H 2O 2 (100 µM added in the bath) increased intracellular sodium concentration ([Na +