PMID- 28472795
OWN - NLM
STAT- MEDLINE
DCOM- 20170620
LR  - 20180609
IS  - 1423-0135 (Electronic)
IS  - 1018-1172 (Linking)
VI  - 54
IP  - 3
DP  - 2017
TI  - Role of Organic Anion Transporters in the Uptake of Protein-Bound Uremic Toxins 
      by Human Endothelial Cells and Monocyte Chemoattractant Protein-1 Expression.
PG  - 170-179
LID - 10.1159/000468542 [doi]
AB  - Organic anion transporters (OATs) are involved in the uptake of uremic toxins 
      such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS), which play a role in 
      endothelial dysfunction in patients with chronic kidney diseases (CKD). In this 
      study, we investigated the role of OAT1 and OAT3 in the uptake of PCS and IS into 
      human endothelial cells. PCS was synthesized via p-cresol sulfation and 
      characterized using analytical methods. The cells were treated with PCS and IS in 
      the absence and presence of probenecid (Pb), an OAT inhibitor. Cell viability was 
      assessed using the MTT assay. The absorbed toxins were analyzed using 
      chromatography, OAT expression using immunocytochemistry and western blot, and 
      monocyte chemoattractant protein-1 (MCP-1) expression using enzyme-linked 
      immunosorbent assay. Cell viability decreased after toxin treatment in a 
      dose-dependent manner. PCS and IS showed significant internalization after 60 min 
      treatment, while no internalization was observed in the presence of Pb, 
      suggesting that OATs are involved in the transport of both toxins. 
      Immunocytochemistry and western blot demonstrated OAT1 and OAT3 expression in 
      endothelial cells. MCP-1 expression increased after toxins treatment but 
      decreased after Pb treatment. PCS and IS uptake were mediated by OATs, and OAT 
      blockage could serve as a therapeutic strategy to inhibit MCP-1 expression.
CI  - (c) 2017 S. Karger AG, Basel.
FAU - Favretto, Giane
AU  - Favretto G
AD  - Experimental Nephrology Laboratory, Basic Pathology Department, Universidade 
      Federal do Parana, Curitiba, Brazil.
FAU - Souza, Lauro M
AU  - Souza LM
FAU - Gregorio, Paulo C
AU  - Gregorio PC
FAU - Cunha, Regiane S
AU  - Cunha RS
FAU - Maciel, Rayana A P
AU  - Maciel RAP
FAU - Sassaki, Guilherme L
AU  - Sassaki GL
FAU - Toledo, Maria G
AU  - Toledo MG
FAU - Pecoits-Filho, Roberto
AU  - Pecoits-Filho R
FAU - Souza, Wesley M
AU  - Souza WM
FAU - Stinghen, Andrea E M
AU  - Stinghen AEM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170505
PL  - Switzerland
TA  - J Vasc Res
JT  - Journal of vascular research
JID - 9206092
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cresols)
RN  - 0 (Organic Anion Transport Protein 1)
RN  - 0 (Organic Anion Transporters, Sodium-Independent)
RN  - 0 (Sulfuric Acid Esters)
RN  - 0 (organic anion transport protein 3)
RN  - 56M34ZQY1S (4-cresol sulfate)
RN  - N187WK1Y1J (Indican)
RN  - PO572Z7917 (Probenecid)
SB  - IM
MH  - Biological Transport
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Chemokine CCL2/*metabolism
MH  - Cresols/metabolism/toxicity
MH  - Dose-Response Relationship, Drug
MH  - Endothelial Cells/drug effects/*metabolism/pathology
MH  - Humans
MH  - Indican/metabolism/toxicity
MH  - Organic Anion Transport Protein 1/antagonists & inhibitors/*metabolism
MH  - Organic Anion Transporters, Sodium-Independent/antagonists & 
      inhibitors/*metabolism
MH  - Probenecid/pharmacology
MH  - Sulfuric Acid Esters/metabolism/toxicity
MH  - Time Factors
MH  - Up-Regulation
MH  - Uremia/*metabolism/pathology
OTO - NOTNLM
OT  - Chronic kidney disease
OT  - Endothelial dysfunction
OT  - Monocyte chemoattractant protein-1
OT  - Organic anion transporters
OT  - Uremic toxins
EDAT- 2017/05/05 06:00
MHDA- 2017/06/21 06:00
CRDT- 2017/05/05 06:00
PHST- 2016/08/31 00:00 [received]
PHST- 2017/03/05 00:00 [accepted]
PHST- 2017/05/05 06:00 [pubmed]
PHST- 2017/06/21 06:00 [medline]
PHST- 2017/05/05 06:00 [entrez]
AID - 000468542 [pii]
AID - 10.1159/000468542 [doi]
PST - ppublish
SO  - J Vasc Res. 2017;54(3):170-179. doi: 10.1159/000468542. Epub 2017 May 5.