Increased renal elimination of endogenous and synthetic pyrimidine nucleosides in concentrative nucleoside transporter 1 deficient mice.
Increased renal elimination of endogenous and synthetic pyrimidine nucleosides in concentrative nucleoside transporter 1 deficient mice.
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DOI：
10.1038/s41467-023-38789-8
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发表时间：
2023-06-01
影响因子：
16.6
通讯作者：
Govindarajan, Rajgopal
中科院分区：
文献类型：
--
作者：
Persaud, Avinash K. K.;Bernier, Matthew C. C.;Massey, Michael A. A.;Agrawal, Shipra;Kaur, Tejinder;Nayak, Debasis;Xie, Zhiliang;Weadick, Brenna;Raj, Ruchika;Hill, Kasey;Abbott, Nicole;Joshi, Arnav;Anabtawi, Nadeen;Bryant, Claire;Somogyi, Arpad;Cruz-Monserrate, Zobeida;Amari, Foued;Coppola, Vincenzo;Sparreboom, Alex;Bakfer, Sharyn D. D.;Unadkat, Jashvant D. D.;Phelps, Mitch A. A.;Govindarajan, Rajgopal
Concentrative nucleoside transporters (CNTs) are active nucleoside influx systems, but their in vivo roles are poorly defined. By generating CNT1 knockout (KO) mice, here we identify a role of CNT1 in the renal reabsorption of nucleosides. Deletion of CNT1 in mice increases the urinary excretion of endogenous pyrimidine nucleosides with compensatory alterations in purine nucleoside metabolism. In addition, CNT1 KO mice exhibits high urinary excretion of the nucleoside analog gemcitabine (dFdC), which results in poor tumor growth control in CNT1 KO mice harboring syngeneic pancreatic tumors. Interestingly, increasing the dFdC dose to attain an area under the concentration-time curve level equivalent to that achieved by wild-type (WT) mice rescues antitumor efficacy. The findings provide new insights into how CNT1 regulates reabsorption of endogenous and synthetic nucleosides in murine kidneys and suggest that the functional status of CNTs may account for the optimal action of pyrimidine nucleoside analog therapeutics in humans. Concentrative nucleoside transporters (CNTs) are cellular nucleoside influx systems, but their in vivo roles are poorly defined. By generating CNT1 knockout (KO) mice, here the authors show a role of CNT1 in the renal reabsorption of endogenous and synthetic nucleosides.
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影响因子：
5.6
作者：
Fasullo M;Endres L
通讯作者：
Endres L
影响因子：
1.3
作者：
Jaramillo, Adrian Christopher;Hubeek, Isabelle;Peters, Godefridus J.
通讯作者：
Peters, Godefridus J.
影响因子：
5.8
作者：
AHMED, NK;HAGGITT, RC;WELCH, AD
通讯作者：
WELCH, AD
DOI：
10.1152/ajpregu.00293.2007
发表时间：
2007-11-01
影响因子：
2.8
作者：
Govindarajan, Rajgopal;Bakken, Aimee H.;Unadkat, Jashvant D.
通讯作者：
Unadkat, Jashvant D.
影响因子：
19.6
作者：
Dunn, SR;Qi, ZH;Sharma, K
通讯作者：
Sharma, K