Mutual role of ecto-5'-nucleotidase/CD73 and concentrative nucleoside transporter 3 in the intestinal uptake of dAMP
Autoři:
Katsuya Narumi aff001; Tsukika Ohata aff001; Yuichi Horiuchi aff001; Hiroshi Satoh aff002; Ayako Furugen aff001; Masaki Kobayashi aff003; Ken Iseki aff001
Působiště autorů:
Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan
aff001; Research and Development Division, Hokkaido Research Institute, Nissei Bio Co. Ltd, Eniwa, Hokkaido, Japan
aff002; Department of Pharmacy, Hokkaido University Hospital, Sapporo, Hokkaido, Japan
aff003
Vyšlo v časopise:
PLoS ONE 14(10)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0223892
Souhrn
2'-Deoxyadenosine 5'-monophosphate (dAMP), a deoxyribonucleotide found in DNA, affects intestinal cell growth. The molecular mechanisms underlying gastrointestinal absorption of foreign DNA ingested along with food has hardly been investigated. The aim of this study was to investigate the mechanism underlying intestinal absorption of dAMP. The uptake of [3H]dAMP by Caco-2 cells was Na+- and pH-dependent and was inhibited by various nucleosides. In contrast, nitrobenzylthioinosine (NMBPR), an equilibrative nucleoside transporter inhibitor, showed little inhibitory effects on [3H]dAMP uptake. Additionally, human concentrative nucleoside transporter (CNT) 3, transiently expressed in COS-7 cells, mediated the uptake of [3H]dAMP. A kinetic study revealed that the Km value of CNT3-mediated uptake of dAMP (59.6 μM) was close to that of 2'-deoxyadenosine (dAdo) (56.3 μM), whereas the dAMP Vmax (15.6 pmol·mg protein–1min–1) was 500-fold lesser than the dAdo Vmax (7782 pmol·mg protein–1min–1). Further, [3H]dAMP uptake was greater in COS-7 cells expressing ecto-5'-nucleotidase/CD73 with CNT3 than in those expressing CNT3 alone. These data suggest that, although dAMP is a substrate of CNT3, it is dephosphorylated to dAdo by CD73 and is efficiently absorbed as dAdo from the intestinal lumen.
Klíčová slova:
Phosphates – Cell membranes – Gastrointestinal tract – Ileum – Caco-2 cells – Purines – Nucleosides – Pyrimidines
Zdroje
1. Hess JR, Greenberg NA. The role of nucleotides in the immune and gastrointestinal systems: potential clinical applications. Nutr Clin Pract. 2012; 27: 281–294. doi: 10.1177/0884533611434933 22392907
2. Holen E, Johsson R. Dietary nucleotides and intestinal cell lines. I. Modulation of growth. Nutr Res. 2004; 24: 197–207.
3. Uauy R, Quan R, Gil A. Role of nucleotides in intestinal development and repair: implications for infant nutrition. J Nutr. 1994; 124: 1436S–1441S. doi: 10.1093/jn/124.suppl_8.1436S 8064399
4. Anderson CM, Parkinson FE. Potential signalling roles for UTP and UDP: sources, regulation and release of uracil nucleotides. Trends Pharmacol Sci. 1997; 18: 387–392. doi: 10.1016/s0165-6147(97)01106-1 9357323
5. Carver JD. Dietary nucleotides: effects on the immune and gastrointestinal systems. Acta Paediatr Suppl. 1999; 88: 83–88.
6. Sánchez-Pozo A, Gil A. Nucleotides as semiessential nutritional components. Br J Nutr. 2002; 87: S135–S137. doi: 10.1079/bjn2001467 11895150
7. Baldwin SA, Beal PR, Yao SY, King AE, Cass CE, Young JD. The equilibrative nucleoside transporter family, SLC29. Pflugers Arch. 2004; 447: 735–743. doi: 10.1007/s00424-003-1103-2 12838422
8. Gray JH, Owen RP, Giacomini KM. The concentrative nucleoside transporter family, SLC28. Pflugers Arch. 2004; 447: 728–734. doi: 10.1007/s00424-003-1107-y 12856181
9. Smith KM, Slugoski MD, Loewen SK, Ng AM, Yao SY, Chen XZ, et al. The broadly selective human Na+/nucleoside cotransporter (hCNT3) exhibits novel cation-coupled nucleoside transport characteristics. J Biol Chem. 2005; 280: 25436–25449. doi: 10.1074/jbc.M409454200 15870078
10. Young JD, Yao SY, Sun L, Cass CE, Baldwin SA. Human equilibrative nucleoside transporter (ENT) family of nucleoside and nucleobase transporter proteins. Xenobiotica. 2008; 38: 995–1021. doi: 10.1080/00498250801927427 18668437
11. Ward JL, Sherali A, Mo ZP, Tse CM. Kinetic and pharmacological properties of cloned human equilibrative nucleoside transporters, ENT1 and ENT2, stably expressed in nucleoside transporter-deficient PK15 cells. Ent2 exhibits a low affinity for guanosine and cytidine but a high affinity for inosine. J Biol Chem. 2000; 275: 8375–8381. doi: 10.1074/jbc.275.12.8375 10722669
12. Engel K, Zhou M, Wang J. Identification and characterization of a novel monoamine transporter in the human brain. J Biol Chem. 2004; 279: 50042–50049. doi: 10.1074/jbc.M407913200 15448143
13. Barnes K, Dobrzynski H, Foppolo S, Beal PR, Ismat F, Scullion ER, et al. Distribution and functional characterization of equilibrative nucleoside transporter-4, a novel cardiac adenosine transporter activated at acidic pH. Circ Res. 2006; 99: 510–519. doi: 10.1161/01.RES.0000238359.18495.42 16873718
14. Griffith DA, Jarvis SM. Nucleoside and nucleobase transport systems of mammalian cells. Biochim Biophys Acta. 1996; 1286: 153–181. doi: 10.1016/s0304-4157(96)00008-1 8982282
15. Lai Y, Bakken AH, Unadkat JD. Simultaneous expression of hCNT1-CFP and hENT1-YFP in Madin-Darby canine kidney cells. Localization and vectorial transport studies. J Biol Chem. 2002; 277: 37711–37717. doi: 10.1074/jbc.M204986200 12097333
16. Strohmeier GR, Lencer WI, Patapoff TW, Thompson LF, Carlson SL, Moe SJ, et al. Surface expression, polarization, and functional significance of CD73 in human intestinal epithelia. J Clin Invest. 1997; 99: 2588–2601. doi: 10.1172/JCI119447 9169488
17. Zimmermann H, Braun N. Ecto-nucleotidases—molecular structures, catalytic properties, and functional roles in the nervous system. Prog Brain Res. 1999; 120: 371–385. 10551012
18. Resta R, Yamashita Y, Thompson LF. Ecto-enzyme and signaling functions of lymphocyte CD73. Immunol Rev. 1998; 161: 95–109. doi: 10.1111/j.1600-065x.1998.tb01574.x 9553767
19. Colgan SP, Eltzschig HK, Eckle T, Thompson LF. Physiological roles for ecto-5'-nucleotidase (CD73). Purinergic Signal. 2006; 2: 351–360. doi: 10.1007/s11302-005-5302-5 18404475
20. Antonioli L, Yegutkin GG, Pacher P, Blandizzi C, Haskó G. Anti-CD73 in cancer immunotherapy: awakening new opportunities. Trends Cancer. 2016; 2: 95–109. doi: 10.1016/j.trecan.2016.01.003 27014745
21. Crane JK, Shulgina I, Naeher TM. Ecto-5'-nucleotidase and intestinal ion secretion by enteropathogenic Escherichia coli. Purinergic Signal. 2007; 3: 233–246. doi: 10.1007/s11302-007-9056-0 18404437
22. Hu H, Endres CJ, Chang C, Umapathy NS, Lee EW, Fei YJ, et al. Electrophysiological characterization and modeling of the structure activity relationship of the human concentrative nucleoside transporter 3 (hCNT3). Mol Pharmacol. 2006; 69: 1542–1553. doi: 10.1124/mol.105.018945 16446384
23. Wilson DW, Wilson TH. Intestinal absorption in vitro of uridylic and thymidylic acids. Biochim Biophys Acta. 1956; 22: 587. doi: 10.1016/0006-3002(56)90079-8 13382898
24. Wilson DW, Wilson HC. Studies in vitro of the digestion and absorption of purine ribonucleotides by the intestine. J Biol Chem. 1962; 237: 1643–1647. 14007338
25. Han TK, Proctor WR, Costales CL, Cai H, Everett RS, Thakker DR. Four cation-selective transporters contribute to apical uptake and accumulation of metformin in Caco-2 cell monolayers. J Pharmacol Exp Ther. 2015; 352: 519–528. doi: 10.1124/jpet.114.220350 25563903
26. Zhou M, Duan H, Engel K, Xia L, Wang J. Adenosine transport by plasma membrane monoamine transporter: reinvestigation and comparison with organic cations. Drug Metab Dispos. 2010; 38: 1798–1805. doi: 10.1124/dmd.110.032987 20592246
27. Ritzel MW, Yao SY, Huang MY, Elliott JF, Cass CE, Young JD. Molecular cloning and functional expression of cDNAs encoding a human Na+-nucleoside cotransporter (hCNT1). Am J Physiol. 1997; 272: C707–C714. doi: 10.1152/ajpcell.1997.272.2.C707 9124315
28. Nagai K, Nagasawa K, Koma M, Hotta A, Fujimoto S. Cytidine is a novel substrate for wild-type concentrative nucleoside transporter 2. Biochem Biophys Res Commun 2006; 347: 439–443. doi: 10.1016/j.bbrc.2006.06.103 16828706
29. Wang C, Pimple S, Buolamwini JK. Interaction of benzopyranone derivatives and related compounds with human concentrative nucleoside transporters 1, 2 and 3 heterologously expressed in porcine PK15 nucleoside transporter deficient cells. Structure-activity relationships and determinants of transporter affinity and selectivity. Biochem Pharmacol. 2010; 79: 307–320. doi: 10.1016/j.bcp.2009.08.028 19735647
30. Ward JL, Tse CM. Nucleoside transport in human colonic epithelial cell lines: evidence for two Na+-independent transport systems in T84 and Caco-2 cells. Biochim Biophys Acta 1999; 1419: 15–22. doi: 10.1016/s0005-2736(99)00045-0 10366666
31. Belt JA, Marina NM, Phelps DA, Crawford CR. Nucleoside transport in normal and neoplastic cells. Adv Enzyme Regul. 1993; 33: 235–252. 8356910
32. Young JD, Yao SY, Baldwin JM, Cass CE, Baldwin SA. The human concentrative and equilibrative nucleoside transporter families, SLC28 and SLC29. Mol Aspects Med. 2013; 34: 529–547. doi: 10.1016/j.mam.2012.05.007 23506887
33. Ritzel MW, Ng AM, Yao SY, Graham K, Loewen SK, Smith KM, et al. Molecular identification and characterization of novel human and mouse concentrative Na+-nucleoside cotransporter proteins (hCNT3 and mCNT3) broadly selective for purine and pyrimidine nucleosides (system cib). J Biol Chem. 2001; 276: 2914–2927. doi: 10.1074/jbc.M007746200 11032837
34. Ellis JA, Jackman MR, Luzio JP. The post-synthetic sorting of endogenous membrane proteins examined by the simultaneous purification of apical and basolateral plasma membrane fractions from Caco-2 cells. Biochem J. 1992; 283: 553–560. doi: 10.1042/bj2830553 1315518
35. Kukulski F, Lévesque SA, Lavoie EG, Lecka J, Bigonnesse F, Knowles AF, et al. Comparative hydrolysis of P2 receptor agonists by NTPDases 1, 2, 3 and 8. Purinergic Signal. 2005; 1: 193–204. doi: 10.1007/s11302-005-6217-x 18404504
36. Fausther M, Lavoie EG, Goree JR, Baldini G, Dranoff JA. NT5E mutations that cause human disease are associated with intracellular mistrafficking of NT5E protein. PLoS One. 2014; 9: e98568. doi: 10.1371/journal.pone.0098568 24887587
37. Graham KA, Leithoff J, Coe IR, Mowles D, Mackey JR, Young JD, et al. Differential transport of cytosine-containing nucleosides by recombinant human concentrative nucleoside transporter protein hCNT1. Nucleosides Nucleotides Nucleic Acids. 2000;19: 415–434. doi: 10.1080/15257770008033018 10772724
38. Gerstin KM, Dresser MJ, Giacomini KM. Specificity of human and rat orthologs of the concentrative nucleoside transporter, SPNT. Am J Physiol Renal Physiol. 2002; 283: F344–F349. doi: 10.1152/ajprenal.00274.2001 12110519
39. Pastor-Anglada M, Urtasun N, Pérez-Torras S. Intestinal Nucleoside Transporters: Function, Expression, and Regulation. Compr Physiol. 2018; 8: 1003–1017. doi: 10.1002/cphy.c170039 29978890
40. Nugent SG, Kumar D, Rampton DS, Evans DF. Intestinal luminal pH in inflammatory bowel disease: possible determinants and implications for therapy with aminosalicylates and other drugs. Gut. 2001; 48: 571–577. doi: 10.1136/gut.48.4.571 11247905
41. Zimmermann H. 5'-Nucleotidase: molecular structure and functional aspects. Biochem J. 1992; 285: 345–365. doi: 10.1042/bj2850345 1637327
Článok vyšiel v časopise
PLOS One
2019 Číslo 10
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Nejasný stín na plicích – kazuistika
- Masturbační chování žen v ČR − dotazníková studie
- Těžké menstruační krvácení může značit poruchu krevní srážlivosti. Jaký management vyšetření a léčby je v takovém případě vhodný?
- Fixní kombinace paracetamol/kodein nabízí synergické analgetické účinky
Najčítanejšie v tomto čísle
- Correction: Low dose naltrexone: Effects on medication in rheumatoid and seropositive arthritis. A nationwide register-based controlled quasi-experimental before-after study
- Combining CDK4/6 inhibitors ribociclib and palbociclib with cytotoxic agents does not enhance cytotoxicity
- Experimentally validated simulation of coronary stents considering different dogboning ratios and asymmetric stent positioning
- Risk factors associated with IgA vasculitis with nephritis (Henoch–Schönlein purpura nephritis) progressing to unfavorable outcomes: A meta-analysis