scholarly journals Expression of Organic Anion Transporter 1 or 3 in Human Kidney Proximal Tubule Cells Reduces Cisplatin Sensitivity

2018 ◽  
Vol 46 (5) ◽  
pp. 592-599 ◽  
Author(s):  
Tom T. G. Nieskens ◽  
Janny G. P. Peters ◽  
Dina Dabaghie ◽  
Daphne Korte ◽  
Katja Jansen ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Organic Anion ◽  
Human Kidney ◽  
Organic Anion Transporter ◽  
Proximal Tubule Cells ◽  
Kidney Proximal Tubule ◽  
Anion Transporter ◽  
Cisplatin Sensitivity ◽  
Tubule Cells

Renal organic anion transporter 1 is maldistributed and diminishes in proximal tubule cells but increases in vasculature after ischemia and reperfusion

2008 ◽  
Vol 295 (6) ◽  
pp. F1807-F1816 ◽  
Author(s):  
Osun Kwon ◽  
Wei-Wei Wang ◽  
Shane Miller
Keyword(s):  
Proximal Tubule ◽  
Ischemia Reperfusion ◽  
Organic Anion ◽  
Basolateral Membrane ◽  
Kidney Injury ◽  
Organic Anion Transporter ◽  
Membrane Domain ◽  
Proximal Tubule Cells ◽  
Anion Transporter ◽  
Tubule Cells

Renal solute clearances are reduced in ischemic acute kidney injury. However, the mechanisms explaining how solute clearance is impaired have not been clarified. Recently, we reported that cadaveric renal allografts exhibit maldistribution of organic anion transporter 1 (OAT1) in proximal tubule cells after ischemia and reperfusion, resulting in impairment of PAH clearance. In the present study, we characterized renal OAT1 in detail after ischemia-reperfusion using a rat model. We analyzed renal OAT1 using confocal microscopy with a three-dimensional reconstruction of serial optical images, Western blot, and quantitative real-time RT-PCR. OAT1 was distributed to basolateral membranes of proximal tubule cells in controls. With ischemia, OAT1 decreased in basolateral membrane, especially in the lateral membrane domain, and appeared diffusely in cytoplasm. After reperfusion following 60-min ischemia, OAT1 often formed cytoplasmic aggregates. The staining for OAT1 started reappearing in lateral membrane domain 1 h after reperfusion. The basolateral membrane staining was relatively well discernable at 240 h of reperfusion. Of note, a distinct increase in OAT1 expression was noted in vasculature early after ischemia and after reperfusion. The total amount of OAT1 protein expression in the kidney diminished after ischemia-reperfusion in a duration-dependent manner until 72 h, when they began to recover. However, even at 240 h, the amount of OAT1 did not reach control levels. The kidney tissues tended to show a remarkable but transient increase in mRNA expression for OAT1 at 5 min of ischemia. Our findings may provide insights of renal OAT1 in its cellular localization and response during ischemic acute kidney injury and recovery from it.

scholarly journals Peritubular transport of ochratoxin A by single rabbit renal proximal tubules.

1998 ◽  
Vol 9 (11) ◽  
pp. 1973-1982 ◽  
Author(s):  
J R Welborn ◽  
C E Groves ◽  
S H Wright
Keyword(s):  
Proximal Tubule ◽  
Ochratoxin A ◽  
Organic Anion ◽  
High Capacity ◽  
Organic Anion Transporter ◽  
Epifluorescence Microscopy ◽  
Proximal Tubule Cells ◽  
Anion Transporter ◽  
Uptake Medium ◽  
Proximal Tubule Segments

Epifluorescence microscopy was used to study peritubular transport of the fluorescent mycotoxin ochratoxin A (OTA) into single proximal tubule segments of the rabbit. Initial rates of OTA uptake into S2 segments were saturable and adequately described by Michaelis-Menten kinetics, with an apparent Km of 2.2+/-0.3 microM (SEM). Several lines of evidence indicated that peritubular uptake of OTA in S2 segments was effectively limited to the "classical" organic anion transporter. First, 5 mM p-aminohippurate (PAH) cis-inhibited the uptake of 1 microM OTA into tubules by 96%. Kinetic analysis of the inhibition of OTA uptake by PAH (100 microM to 5 mM) yielded an apparent Ki of 164 microM, similar to the 100 to 200 microM range of Km values previously reported for the peritubular uptake of PAH. Second, efflux of OTA from tubules was trans-stimulated 3.2-fold by the presence of 2.5 mM PAH in the uptake medium. Third, 100 microM alpha-ketoglutarate (alphaKG) trans-stimulated the uptake rate of 1 microM OTA by 1.8-fold. Fourth, besides PAH, other organic anions effectively cis-inhibited the uptake of 1 microM OTA into tubules (inhibitor, % inhibition): 1.5 mM alphaKG, 80%; 1 mM probenecid, 100%; 1 mM piroxicam, 100%; 1 mM octanoate, 100%. In contrast, 1.5 mM tetraethylammonium, an organic cation, blocked uptake of 1 microM OTA by only 7%. The inhibition of OTA uptake into S1 and S3 segments of the proximal tubule was qualitatively similar: 5 mM PAH cis-inhibited the uptake of 1 microM OTA by approximately 95% in both S1 and S3 segments. Thus, peritubular OTA uptake into all segments of the proximal tubule appears to be dominated by its interaction with the classical organic anion transporter. The high-affinity and relatively high capacity of this pathway for OTA suggest that peritubular uptake may be a significant avenue for the entry of this toxin into proximal tubule cells.

Etoposide Induces Necrosis Through p53-Mediated Antiapoptosis in Human Kidney Proximal Tubule Cells

2015 ◽  
Vol 148 (1) ◽  
pp. 204-219 ◽  
Author(s):  
Hyuk-Kwon Kwon ◽  
Hyeon-Jun Shin ◽  
Jae-Hyeok Lee ◽  
Seol-Hee Park ◽  
Min-Cheol Kwon ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Human Kidney ◽  
Proximal Tubule Cells ◽  
Kidney Proximal Tubule ◽  
Tubule Cells

scholarly journals Etoposide induced cytotoxicity mediated by ROS and ERK in human kidney proximal tubule cells

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Hyeon-Jun Shin ◽  
Hyuk-Kwon Kwon ◽  
Jae-Hyeok Lee ◽  
Muhammad Ayaz Anwar ◽  
Sangdun Choi
Keyword(s):  
Proximal Tubule ◽  
Human Kidney ◽  
Proximal Tubule Cells ◽  
Kidney Proximal Tubule ◽  
Tubule Cells

Human kidney proximal tubule cells are vulnerable to the effects of Rauwolfia serpentina

2015 ◽  
Vol 31 (6) ◽  
pp. 285-293 ◽  
Author(s):  
Miriam E. Mossoba ◽  
Thomas J. Flynn ◽  
Sanah Vohra ◽  
Paddy L. Wiesenfeld ◽  
Robert L. Sprando
Keyword(s):  
Proximal Tubule ◽  
Human Kidney ◽  
Proximal Tubule Cells ◽  
Kidney Proximal Tubule ◽  
Rauwolfia Serpentina ◽  
Tubule Cells
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