scholarly journals Uremic Toxin Indoxyl Sulfate Impairs Hydrogen Sulfide Formation in Renal Tubular Cells

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Chien‐Lin Lu ◽  
Ming‐Chieh Ma
Keyword(s):  
Hydrogen Sulfide ◽  
Indoxyl Sulfate ◽  
Uremic Toxin ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Renal Tubular

scholarly journals TRPV1 Hyperfunction Involved in Uremic Toxin Indoxyl Sulfate-Mediated Renal Tubular Damage

2020 ◽  
Vol 21 (17) ◽  
pp. 6212 ◽  
Author(s):  
Chien-Lin Lu ◽  
Chun-Hou Liao ◽  
Kuo-Cheng Lu ◽  
Ming-Chieh Ma
Keyword(s):  
Transient Receptor Potential ◽  
Mdck Cells ◽  
Indoxyl Sulfate ◽  
Transient Receptor Potential Vanilloid ◽  
Tubular Damage ◽  
Uremic Toxin ◽  
Dependent Manner ◽  
Renal Tubular Damage ◽  
Tubular Cells ◽  
Renal Tubular

Indoxyl sulfate (IS) is accumulated during severe renal insufficiency and known for its nephrotoxic properties. Transient receptor potential vanilloid 1 (TRPV1) is present in the kidney and acts as a renal sensor. However, the mechanism underlying IS-mediated renal tubular damage in view of TRPV1 is lacking. Here, we demonstrated that TRPV1 was expressed in tubular cells of Lilly Laboratories cell-porcine kidney 1 (LLC-PK1) and Madin-Darby canine kidney cells (MDCK). IS treatment in both cells exhibited tubular damage with increased LDH release and reduced cell viability in dose- and time-dependent manners. MDCK, however, was more vulnerable to IS. We, therefore, investigated MDCK cells to explore a more detailed mechanism. Interestingly, IS-induced tubular damage was markedly attenuated in the presence of selective TRPV1 blockers. IS showed no effect on TRPV1 expression but significantly increased arachidonate 12-lipoxygenase (ALOX12) protein, mRNA expression, and 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) amounts in a dose-dependent manner, indicating that the ALOX12/12(S)-HETE pathway induced TRPV1 hyperfunction in IS-mediated tubulotoxicity. Blockade of ALOX12 by cinnamyl-3,4-dihydroxy-α-cyanocinnamate or baicalein attenuated the effects of IS. Since aryl hydrocarbon receptor (AhR) activation after IS binding is crucial in mediating cell death, here, we found that the AhR blockade not only ameliorated tubular damage but also attenuated ALOX12 expression and 12(S)-HETE production caused by IS. The uremic toxic adsorbent AST-120, however, showed little effect on ALOX12 and 12(S)-HETE, as well as IS-induced cell damage. These results clearly indicated that IS activated AhR and then upregulated ALOX12, and this induced endovanilloid 12(S)-HETE synthesis and contributed to TRPV1 hyperfunction in IS-treated tubular cells. Further study on TRPV1 may attenuate kidney susceptibility to the functional loss of end-stage kidney disease via IS.

scholarly journals D-serine, a novel uremic toxin, induces senescence in human renal tubular cells via GCN2 activation

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Akira Okada ◽  
Masaomi Nangaku ◽  
Tzu-Ming Jao ◽  
Hiroshi Maekawa ◽  
Yu Ishimono ◽  
...  
Keyword(s):  
Uremic Toxin ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Renal Tubular

scholarly journals Human antigen R regulates hypoxia‐induced mitophagy in renal tubular cells through PARKIN/BNIP3L expressions

2021 ◽  
Author(s):  
Shao‐Hua Yu ◽  
Kalaiselvi Palanisamy ◽  
Kuo‐Ting Sun ◽  
Xin Li ◽  
Yao‐Ming Wang ◽  
...  
Keyword(s):  
Tubular Cells ◽  
Human Antigen R ◽  
Renal Tubular Cells ◽  
Renal Tubular

scholarly journals Interleukin-22 attenuates renal tubular cells inflammation and fibrosis induced by TGF-β1 through Notch1 signaling pathway

Renal Failure ◽  
2020 ◽  
Vol 42 (1) ◽  
pp. 381-390 ◽  
Author(s):  
Rong Tang ◽  
Xiangcheng Xiao ◽  
Yang Lu ◽  
Huihui Li ◽  
Qiaoling Zhou ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Tubular Cells ◽  
Interleukin 22 ◽  
Renal Tubular Cells ◽  
Notch1 Signaling ◽  
Renal Tubular ◽  
Notch1 Signaling Pathway ◽  
Tgf Β1
Sign in / Sign up

Export Citation Format

Share Document