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Last update 08 May 2025

CHT

Last update 08 May 2025

Basic Info

Synonyms

CHT, CHT1, hCHT

+ [6]

Introduction

High-affinity Na(+)-coupled choline transmembrane symporter (PubMed:11027560, PubMed:11068039, PubMed:12237312, PubMed:12969261, PubMed:17005849, PubMed:23132865, PubMed:23141292, PubMed:27569547). Functions as an electrogenic, voltage-dependent transporter with variable charge/choline stoichiometry (PubMed:17005849). Choline uptake and choline-induced current is also Cl(-)-dependent where Cl(-) is likely a regulatory ion rather than cotransported ion (PubMed:11068039, PubMed:12237312, PubMed:17005849). Plays a critical role in acetylcholine (ACh) synthesis by taking up the substrate choline from the synaptic cleft into the presynaptic nerve terminals after neurotransmitter release (PubMed:27569547). SLC5A7/CHT1-mediated choline high-affinity transport in cholinergic neurons is the rate-limiting step for production of ACh, thereby facilitating communication by subsequent action potentials (PubMed:11027560). Localized predominantly in presynaptic terminal intracellular organelles, and translocated to the plasma membrane in active form in response to neuronal activity (PubMed:12969261, PubMed:15953352).

Drugs associated with CHT

VU6001221

Target

CHT

Mechanism

CHT blockers

Active Org.-

Originator Org.

Vanderbilt University

Active Indication-

Inactive Indication-

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CHT

100 Translational Medicine associated with CHT

0 Patents (Medical) associated with CHT

529

Literatures (Medical) associated with CHT

01 Apr 2025·Journal for ImmunoTherapy of Cancer

Targeting PD-1 and CD85j can restore intratumoral CD4⁺GzmB⁺T-cell functions to combat MHC-II-expressing tumors

Article

Author: Xiong, Hui ; Wang, Xu ; Fu, Shengling ; Hu, Shaojie ; Tian, Yitao ; Zou, Wenbin ; Wang, Xue ; Yuan, Zhiwei ; Xi, Yu ; Meng, Kelin ; Cai, Yixin ; Li, Lequn ; Yu, Taiyan ; Wang, Boyu ; Fu, Xiangning ; Qu, Rirong ; Wang, Tianlai ; Zeng, Chenxi

BackgroundA subset of CD4+T cells with cytotoxic activity has been identified, and these cells exert their effects by expressing perforin and granzymes. Despite the progress made in characterizing cytotoxic CD4+T cells in various diseases, the status of cytotoxic CD4+T cells in non-small cell lung cancer (NSCLC) and the underlying mechanisms involved in promoting intratumoral cytotoxic CD4+T-cell activation remain unclear.MethodsWe used flow cytometry to examine the phenotypic and functional properties of CD4+GzmB+T cells in the peripheral blood and tumor tissues of patients with NSCLC. Loss-of-function analyses and RNA sequencing were used to identify the underlying mechanisms involved in the effects of interleukin (IL)-15 on the restoration of CD4+GzmB+T-cell function in vitro. A patient-derived lung cancer explant model and an animal model were used to verify the effects of immune checkpoint inhibitors on CD4+GzmB+T-cell activation.ResultsIn patients with NSCLC, impaired cytolytic function of tumor-infiltrated granzyme B (GzmB)-expressing CD4+T cells was restored by IL-15 through activation of the AKT-FOXO1-T-bet axis. Moreover, IL-15 stimulation increased solute carrier family 7 member 5 (SLC7A5) expression in CD4+GzmB+T cells in an Protein Kinase B (AKT)-dependent manner, and inhibition of SLC7A5 abrogated the effect of IL-15 on CD4+GzmB+T cells. Additionally, we showed that the immune checkpoint molecules programmed cell death-1 (PD-1) and CD85j were mutually exclusively expressed in CD4+GzmB+T cells and that dual targeting of PD-1 and CD85j enhanced the effector function of CD4+GzmB+T cells by activating the AKT pathway. Notably, tumor cells expressing major histocompatibility complex (MHC)-II and IL-15 determine the effectiveness of CD4+GzmB+T-cell-mediated antitumor immunity in response to immunotherapy.ConclusionsOur study demonstrated that tumor-infiltrating CD4+GzmB+T cells fail to eliminate tumors. Dual blockade of PD-1 and CD85j alongside IL-15 restores the effector function of CD4+GzmB+T cells and drives CD4+GzmB+T-cell transformation in the tumor microenvironment to combat MHC-II-expressing tumors.

01 Mar 2025·Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology

Effects of nanopolystyrene and/or phoxim exposure on digestive function of Eriocheir sinensis

Article

Author: Zhu, Shuren ; Ma, Yuan ; Zhang, Jun ; Huang, Mengting ; Fan, Qianru ; Li, Xilei ; Che, Shunli ; Ding, Shuquan

Nanopolystyrene (NP) and phoxim (PHO) are pervasive environmental contaminants that pose a significant threat to the health of aquatic organisms, prompting widespread concern among researchers and the public alike. The hepatopancreas play important roles in the Chinese mitten crab (Eriocheir sinensis), such as digestion, absorption and detoxification. This study assessed the hepatopancreatic toxicity caused by the exposure of Eriocheir sinensis to environmentally relevant concentrations of NP and/or PHO. After a 21-day exposure period, NP (1.0 × 10¹⁰ particles/L) and PHO (24 μg/L) exposure resulted in reduced number of blister-like, resorptive, and fibrillar cells and an elevation in lipid droplets within the hepatopancreas compared to the control group. Furthermore, trypsin and lipase activity decreased, amylase activity increased, and a significantly decrease in the expression of digestion-related genes, including CHT, CarL, and CarB, suggested impairment in both digestive and metabolic functions. The marked upregulation of key genes, including PPARγ, GYK, PEPCK, and SCD, as well as key metabolites such as 4-methylzymosterol-carboxylate, zymosterone, lathosterol, 7-dehydro-desmosterol, vitamin D2, 24-methylene-cycloartanol, 5-dehydroepisterol, and sitosterol in the lipid metabolic pathway, showed that the peroxisome proliferator-activated receptor (PPAR) and steroid biosynthesis signaling pathways were highly affected by exposure to NP and/or PHO. These findings indicated that exposure to NP and/or PHO might adversely affect the hepatopancreatic physiological homeostasis in E. sinensis by causing tissue damage and interfering with digestive and metabolic functions. Our results provide ecotoxicological insights into the effects of nanopolystyrene and/or phoxim exposure on the digestive function of Eriocheir sinensis.

01 Mar 2025·Animal Nutrition

Long-term leucine supplementation increases body weight in goats by controlling appetite and muscle protein synthesis under protein-restricted conditions

Article

Author: Yan, Qiongxian ; Jiang, Aoyu ; Wu, Jian ; Lv, Xiaokang ; Zhou, Chuanshe ; Tan, Zhiliang ; Hua, Jinling ; Tang, Shaoxun ; Kang, Jinhe ; Liu, Zixin

An inadequate amino acid (AA) supply in animals under protein-restricted conditions can slow skeletal muscle growth. Protein translation can be activated by short-term leucine (Leu) stimulation; however, whether muscle mass increases under long-term Leu supplementation and how the gut and muscle respond to Leu supplementation are largely unknown. In this study, we investigated if muscle mass increases with long-term Leu supplementation under protein-restricted conditions. We identified changes in the link between the gut and muscles under different amino acid supply conditions, using goats as the study object. A total of 27 Xiangdong black male goats with average initial body weight (BW) of 10.88 ± 1.22 kg were randomly divided into three dietary treatments: a normal protein diet (NP, 14.24% crude protein [CP]); a low protein diet (LP, 8.27% CP with supplemental 1.66% rumen-protected lysine [RPLys] and 0.09% rumen-protected methionine [RPMet]); and LP diet with rumen-protected Leu (RPLeu) (LP + RPLeu, 8.75% CP with supplemental 1.66% RPLys, 0.09% RPMet and 1.46% RPLeu). The animal trial lasted for 110 d, consisting of 20 d of adaptation and a 90 d of experimental period. The results showed that long-term protein restriction increased gut tryptophan hydroxylase 1 (TPH1) activity (P < 0.001), tryptophan (Trp) catabolism (P < 0.001), and 5-hydroxytryptamine (5-HT) synthesis (P < 0.001), which all subsequently reduced goat appetite. Long-term Leu supplementation inhibited 5-HT synthesis (P < 0.001), decreased Trp catabolism in the gut, and increased appetite in goats. Long-term protein restriction enhanced jejunal and ileal branched-chain amino acid transferase (BCAT) (P < 0.001) and branched-chain α-Keto acid dehydrogenase (BCKD) (P = 0.048) activities, which increased branched-chain amino acid (BCAA) catabolism. Immunofluorescence results showed that protein restriction decreased the intestinal mucosal expression of solute carrier family 1 member 5 (SLC1A5) (P = 0.032) and solute carrier family 7 member 5 (SLC7A5) (P < 0.001), reduced BCAA transport from the mucosa to the blood, lowered BCAA levels in the blood (P < 0.001). Western blot results showed that protein restriction inhibited mammalian target of rapamycin (mTOR) pathway activation in goat muscles. Leu supplementation increased BCAA translocation from the intestine to the blood and promoted activation of the muscle mTOR pathway and protein synthesis. In conclusion, our results suggest that Leu supplementation in low-protein diets improves appetite and alleviates the inhibition of muscle protein synthesis in goats.

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CHT

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