AT1 receptor-mediated accumulation of extracellular angiotensin II in proximal tubule cells: role of cytoskeleton microtubules and tyrosine phosphatases

American Journal of Physiology. Renal Physiology
Xiao C LiJia L Zhuo

Abstract

Long-term angiotensin II (ANG II) administration is associated with increased ANG II accumulation in the kidney, but intrarenal compartment(s) involved in this response remains to be determined. We tested the hypothesis that 1) extracellular ANG II is taken up by proximal tubule cells (PTCs) through AT(1) receptor-mediated endocytosis, 2) this process is regulated by cytoskeleton microtubule- and tyrosine phosphatase-dependent mechanisms, and 3) AT(1) receptor-mediated endocytosis of ANG II has a functional relevance by modulating intracellular cAMP signaling. In cultured PTCs, [(125)I]Tyr-labeled ANG II and fluorescein labeled-ANG II were internalized in a time-dependent manner and colocalized with the endosome marker Alexa Fluor 594-transferrin. Endocytosis of extracellular ANG II was inhibited by the AT(1) receptor blocker losartan (16.5 +/- 4.6%, P < 0.01 vs. ANG II, 78.3 +/- 6.2%) and by the tyrosine phosphatase inhibitor phenylarsine oxide (PAO; 30.0 +/- 3.5%, P < 0.05 vs. ANG II). Intracellular ANG II levels were increased by approximately 58% (basal, 229.8 +/- 11.4 vs. ANG II, 361.3 +/- 11.8 pg ANG II/mg protein, P < 0.01), and the responses were blocked by losartan (P < 0.01), the cytoskeleton microtubule inhibitor col...Continue Reading

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Citations

Sep 30, 2008·Antioxidants & Redox Signaling·Ravi NistalaJames R Sowers
Dec 16, 2011·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Brianne EllisJia L Zhuo
Sep 4, 2009·American Journal of Physiology. Renal Physiology·Douglas R YingstWilliam H Beierwaltes
Feb 27, 2009·American Journal of Physiology. Renal Physiology·Weijian ShaoL Gabriel Navar
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Jul 2, 2011·American Journal of Nephrology·Adam Whaley-ConnellJames R Sowers
May 10, 2007·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Jia L Zhuo, Xiao C Li
Dec 6, 2011·Respiratory Physiology & Neurobiology·Jia DengHilary Ma
Feb 17, 2009·Translational Research : the Journal of Laboratory and Clinical Medicine·Ravi NistalaAdam Whaley-Connell
Feb 27, 2007·Medical Hypotheses·Richard N Re, Julia L Cook
Mar 31, 2018·Clinical and Experimental Nephrology·Akira Nishiyama, Hiroyuki Kobori
Nov 3, 2016·American Journal of Physiology. Cell Physiology·Renato O CrajoinasAdriana C C Girardi
Dec 10, 2008·Nature Clinical Practice. Nephrology·Juan Carlos Q Velez
Mar 4, 2017·Journal of the American Society of Nephrology : JASN·Tianxin Yang, Chuanming Xu
Jan 6, 2007·American Journal of Nephrology·Adam T Whaley-ConnellJames R Sowers
Aug 29, 2014·American Journal of Physiology. Renal Physiology·Xiao C LiJia L Zhuo
May 25, 2020·Cell Stress & Chaperones·Patricia G VallésValeria Cacciamani
Mar 31, 2021·Molecular and Cellular Endocrinology·Fitra RiantoMatthew A Sparks

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