Organic Anion Transporters

Organic anion transporting polypeptides (OATP), a member of solute carrier (SLC) superfamily, is considered as an important transmembrane uptake transporters. OATP is involved in the transport of a variety of endo- and xenobiotics (bile acids, bilirubin, prostaglandin, thyroid hormones, steroid hormone conjugates), drugs and toxins in a Na+ and ATP independent manner. Multiple factors (eg. hormones, proinflammatory cytokines, drugs) can affect the distribution, expression and activity of OATPs, leading to an altered accumulation of OATP substrates and related food-drug and drug-drug interactions. Changes in the distribution and expression of OATPs in malignant tissues may be related to the pathological process of cancer, while the modulation epigenetic mechanism also contributes to its distribution patterns. This review describes the factors that can affect the expression or function of OATPs, which may provide a valuable reference for drug development and the clarification of pathogenesis.
Biological Transport ; Humans ; Neoplasms ; Organic Anion Transporters ; physiology ; Xenobiotics

Child ; Humans ; Inflammatory Bowel Diseases ; Organic Anion Transporters/genetics*

OBJECTIVETo investigate the expression of prostaglandin transporter (PGT) in colorectal cancer (CRC) tissues and its relationship with clinicopathological features.

METHODSThe mRNA and protein levels of PGT were determined by real-time PCR, Western blot and immunohistochemical methods in cancer tissues and adjacent normal tissue from 80 patients with colorectal cancer and their relationship with clinicopathological features was analyzed.

RESULTSCompared with the adjacent normal tissue of colorectal cancer, the PGT mRNA relative expression (0.57 ± 0.33 vs. 2.33 ± 1.20) and the PGT protein expression in cancer tissues decreased significantly [PGT/GAPDH 0.45 ± 0.16 vs. 0.78 ± 0.23, integral A 718.7 ± 359.4 vs. 10412.0 ± 6423.3, average A 0.03 ± 0.01 vs. 0.12 ± 0.09, all P<0.01]. Lower mRNA and protein expressions of PGT in colorectal cancer were associated with depth of invasion T3 to T4 and TNM stage III( to IIII( (P<0.01), while not associated with gender, age, tumor location and differentiation degree (all P>0.05).

CONCLUSIONExpression levels of PGT mRNA and protein in colorectal cancer tissue are significantly down-regulation. PGT expression is associated with invasion depth and late stages.

Colorectal Neoplasms ; Down-Regulation ; Humans ; Neoplasm Invasiveness ; Neoplasm Staging ; Organic Anion Transporters ; RNA, Messenger

Calcium-Binding Proteins ; deficiency ; Humans ; Infant ; Male ; Organic Anion Transporters ; deficiency ; Phenylketonurias ; complications ; diagnosis ; etiology

Pachydermoperiostosis is a rare genetic disease characterized by finger clubbing, periostosis, cutis verticis gyrata and pachydermia accompanied by acroosteolysis and hyperhidrosis. Recently, two susceptibility genes, HPGD and SLCO2A1, have been identified, whose protein products are involved in the transportation of prostaglandin and metabolism underlying pachydermoperiostosis. Here the genetic basis of pachydermoperiostosis and its correlation with its clinical phenotype are reviewed, which may provide a reference for basic research and clinic diagnosis for the disease.
Animals ; Humans ; Hydroxyprostaglandin Dehydrogenases ; genetics ; Organic Anion Transporters ; genetics ; Osteoarthropathy, Primary Hypertrophic ; diagnosis ; genetics ; therapy ; Phenotype

Sodium taurocholate cotransporting polypeptide (NTCP) deficiency is an inborn error of bile acid metabolism caused by mutations of SLC10A1 gene. This paper reports the clinical and genetic features of a patient with this disease. A 3.3-month-old male infant was referred to the hospital with the complaint of jaundiced skin and sclera over 3 months. Physical examination revealed moderate jaundice of the skin and sclera. The liver was palpable 3.5 cm below the right subcostal margin with a medium texture. Serum biochemistry analysis revealed markedly elevated bilirubin (predominantly direct bilirubin) and total bile acids (TBA), as well as decreased 25-OH-VitD level. On pathological analysis of the biopsied liver tissue, hepatocyte ballooning and cholestatic multinucleate giant cells were noted. The lobular architecture was distorted. Infiltration of inflammatory cells, predominantly lymphocytes, was seen in the portal tracts. In response to the anti-inflammatory and liver protective drugs as well as fat-soluble vitamins over 2 months, the bilirubin and transaminases levels were improved markedly while the TBA kept elevated. Because of persisting hypercholanemia on the follow-up, SLC10A1 gene analysis was performed at his age of 17.2 months. The child proved to be a homozygote of the reportedly pathogenic variant c.800C>T (p. Ser267Phe), while the parents were both carriers. NTCP deficiency was thus diagnosed. The infant was followed up until 34.3 months old. He developed well in terms of the anthropometric indices and neurobehavioral milestones. The jaundice disappeared completely. The liver size, texture and function indices all recovered. However, the hypercholanemia persisted, and the long-term outcome needs to be observed.
Humans ; Infant ; Male ; Organic Anion Transporters, Sodium-Dependent ; deficiency ; genetics ; Symporters ; deficiency ; genetics

Renal handling of uric acid mainly occurs in the proximal tubule, and bidirectional transport of urate may involve apical absorption via the urate-anion exchanger (URAT1) and basolateral uptake via organic anion transporters (OAT1 and OAT3). In rat kidneys, we investigated whether the protein abundance of URAT1, OAT1, and OAT3 is affected by the increase in uric acid intake. Male Sprague-Dawley rats were randomly divided into control and uric acid-supplemented groups, and uric acid-supplemented rats were given 0.75 g of uric acid per 180 g body weight per day for 8 days. After the animal experiment, kidneys were harvested and semi-quantitative immunoblotting was carried out from cortical homogenates using polyclonal peptide-derived antibodies to URAT1, OAT1, and OAT3. Serum uric acid level showed an increasing tendency (p=0.055) in the uric acid-supplemented rats (2.60+/- 0.27 mg/dL) compared with control rats (1.97+/-0.29 mg/dL), whereas urinary uric acid excretion was not significantly different between the uric acid-supplemented rats (3.27+/-0.40 mg/d) and control rats (2.61+/-0.34 mg/d). URAT1 protein abundance in cortical homogenates was not significantly different between the uric acid-supplemented rats (132+/-14%) and control rats (100+/-7%). However, OAT1 protein abundance was significantly (p<0.05) increased in the uric acid-supplemented rats (148+/-13%) compared with the control rats (100+/-8%). OAT3 protein abundance was not significantly different between the uric acid-supplemented rats (131+/-12%) and control rats (100+/-17%). In conclusion, OAT1 may have a regulatory role in response to the increase in uric acid intake in the rat kidney. The up-regulation of OAT1 would exert stimulation of urinary uric acid excretion and might contribute to protection from hyperuricemia.
Absorption ; Animal Experimentation ; Animals ; Antibodies ; Body Weight ; Humans ; Hyperuricemia ; Immunoblotting ; Kidney* ; Male ; Organic Anion Transport Protein 1 ; Organic Anion Transporters ; Rats* ; Rats, Sprague-Dawley ; Up-Regulation ; Uric Acid*

Organic anion transporter 2 (OATP2) is an uptake transporter located on the basolateral membrane of human hepatocytes. It mediates the transportation of various organic solutes including bilirubin and impacts bilirubin metabolism. It is encoded by the gene of solute carrier organic anion transporter family member 1B1 and the gene variants that inhibit hepatic bilirubin uptake function may reduce the normal functional level of bilirubin elimination and result in neonatal hyperbilirubinemia. In recent years, some studies have indicated that variants of SLCO1B1 are associated with neonatal jaundice. This article reviews the research advance in SLCO1B1 with respect to the structure and function and the relationship between SLCO1B1 mutations and neonatal jaundice.
Glucosephosphate Dehydrogenase Deficiency ; genetics ; Humans ; Infant, Newborn ; Jaundice, Neonatal ; genetics ; Organic Anion Transporters ; genetics ; Polymorphism, Genetic ; Solute Carrier Organic Anion Transporter Family Member 1b1 ; genetics

OBJECTIVETo explore the changes in the PGE(2) and PGI(2), TXA(2) levels and PGT mRNA expression in the intestinal mucosa in scalded rats.

METHODSWistar rats inflicted with TBSA 30% III degree scald were employed as the model. The PGE(2) and PGI(2) and TXA(2) contents in the intestinal mucosa were measured by radioimmunoassay, and the expression of PGT mRNA was detected by in situ hybridization.

RESULTSThe PGE(2) and PGI(2) levels in intestinal mucosa were increased at 12 postburn hours (PBHs) and thereafter decreased dramatically (P < 0.05). The TXA(2) level in intestinal mucosa of scalded rats was obviously higher than that of normal level at 24 and 48 PBHs (P < 0.05), and the expression of PGT mRNA seemed to be increased after scalding.

CONCLUSIONThe decrease of PGE(2) level and the increase of TXA(2) level in the intestinal mucosa of scalded rats might be involved in rat mucosal injury, and PGT played an important role in the regulation of PGs levels.

Animals ; Burns ; metabolism ; pathology ; Intestinal Mucosa ; metabolism ; pathology ; Organic Anion Transporters ; metabolism ; Prostaglandins ; analysis ; RNA, Messenger ; metabolism ; Rats ; Rats, Wistar