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Last update 08 May 2025

GCSH

Last update 08 May 2025

Basic Info

Synonyms

GCSH, Glycine cleavage system H protein, mitochondrial, glycine cleavage system protein H

+ [2]

Introduction

The glycine cleavage system catalyzes the degradation of glycine. The H protein (GCSH) shuttles the methylamine group of glycine from the P protein (GLDC) to the T protein (GCST). Has a pivotal role in the lipoylation of enzymes involved in cellular energetics such as the mitochondrial dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex (DLAT), and the mitochondrial dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex (DLST) (PubMed:36190515).

Drugs associated with GCSH

T-690

Target

GCSH

Mechanism

GCSH inhibitors

Active Org.

Takeda Pharmaceutical Co., Ltd.

Originator Org.

Takeda Pharmaceutical Co., Ltd.

Active Indication

Neurodegenerative Diseases

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GCSH

100 Translational Medicine associated with GCSH

0 Patents (Medical) associated with GCSH

Literatures (Medical) associated with GCSH

01 Dec 2024·Minerva Cardiology and Angiology

Bioinformatics analysis of the role of cuproptosis gene in acute myocardial infarction

Article

Author: Huang, Dongling ; Wang, Fan ; Wang, Wei ; Fang, Chunyun ; Chen, Wenjing ; Wei, Wanxia ; Sun, Shiling

BACKGROUNDImmune infiltration plays a vital role in the course of acute myocardial infarction (AMI). Cuproptosis is a new type of programmed cell death discovered recently. Currently, there is no study on the mechanism of cuproptosis gene regulating immune infiltration in AMI. Therefore, by integrating cuproptosis-related genes and GEO database-related microarray data, this study analyzed the association between cuproptosis genes and immune infiltration and built a risk model.METHODSThe GSE59867 was used to extract cuproptosis gene expression profile. The R limma package was used to analyze the differentially expressed genes associated with AMI-Cuproptosis. The risk model was constructed according to AMI-cuproptosis differentially expressed genes. Prediction of AMI-cuproptosis-related gene drugs through Coremine Medical database. The upstream miRNAs were predicted using miRWalk, TargetScan, and miRDB libraries, and a miRNA-mRNA network was constructed.RESULTSCuproptosis-related genes (DLST, LIAS, DBT, ATP7A, LIPT1, PDHB, GCSH, DLD, DLAT) were down-regulated in AMI patients. One (ATP7B) gene was up-regulated in AMI patients (P<0.05). These 10 Cuproptosis-related genes were significantly associated with immune cell infiltration. Based on these 10 differential genes, the AMI risk prediction model was constructed, and the AUC value was 0.825, among which the abnormal expression of DLST was a risk factor for AMI. Additionally, we also predicted DLAT upstream miRNAs and associated drug targets, finding that 9 miRNAs were upstream of DLST.CONCLUSIONSDLST is a potential cuproptosis gene associated with AMI, but its specific mechanism remains unclear and requires further investigation in future studies.

01 Dec 2024·International Immunopharmacology

Co-Colorectal cancer stem cells employ the FADS1/DDA axis to evade NK cell-mediated immunosuppression after co-cultured with NK cells under hypoxia

Article

Author: Geng, Shan ; Zhu, Lei ; Shi, Shan ; Yu, Shaohong ; Yu, Caiyu ; Liu, Qiang ; Wang, Yanping

Colorectal cancer (CRC) ranks as China's second most common cancer and fifth top cancer death cause. The study highlights the role of Natural Killer (NK) cells in targeting cancer stem cells (CSCs) that evade immune responses in CRC. Colorectal cancer stem cells (CCSCs) were stem from HT-29 cells and co-cultured with NK cells under normoxic or hypoxic conditions. The impact of this co-culture was evaluated using CCK8 assays for NK cell viability, ELISA for cytokine level changes, and flow cytometry for assessing NK cell apoptosis and activation. Comprehensive metabolomic and transcriptomic analyses were also performed to identify key genes and metabolites involved in the interaction between CCSCs and NK cells Co-culture of CCSCs with NK cells under hypoxia reduced NK cytotoxicity, increased NK apoptosis, and altered cytokine secretion by decreasing IFN-γ and TNF-α levels while increasing IL-6. Transcriptomic and metabolomic analysis identified 4 genes (FADS1, ALDH3A2, GCSH, MTCL1) and 3 metabolites (glyoxylic acid, spermine, DDA) as significant. Interfering with FADS1 counteracted the suppression of IFN-γ and TNF-α induced by CSC cells. Curiously, this inhibition caused by si-FADS1 could be neutralized by the addition of exogenous DDA. Co-culturing with NK cells notably increased spermine levels. Exogenous spermine resulted in a significant reduction in HT-29 cell death rates at 32 µM, 64 µM, and 128 µM, compared to NK cells without spermine. Our research explored CCSCs employed the FADS1/DDA axis to evade NK cell-mediated immunosuppression after co-cultured with NK cells under hypoxia.

01 Dec 2024·Diabetes, Obesity and Metabolism

Associations between cuprotosis‐related genes and the spectrum of metabolic dysfunction‐associated fatty liver disease: An exploratory study

Article

Author: Chen, Sui‐Dan ; Zhang, Xin‐Lei ; Zheng, Ming‐Hua ; Li, Ke ; Byrne, Christopher D. ; Zhou, Meng ; Targher, Giovanni ; Tian, Na ; Wang, Fudi ; Jin, Xin‐Zhe ; Chen, Li‐Li ; Li, Gang ; George, Jacob ; Song, Zi‐Jun ; Feng, Gong ; Yuan, Hai‐Yang ; Liu, Wen‐Yue

AbstractAimsTo explore the associations between cuprotosis‐related genes (CRGs) across different stages of liver disease in metabolic dysfunction‐associated fatty liver disease (MAFLD), including hepatocellular carcinoma (HCC).Materials and MethodsWe analysed several bulk RNA sequencing datasets from patients with MAFLD (n = 331) and MAFLD‐related HCC (n = 271) and two MAFLD single‐cell RNA sequencing datasets. To investigate the associations between CRGs and MAFLD, we performed differential correlation, logistic regression and functional enrichment analyses. We also validated the findings in an independent Wenzhou PERSONS cohort of MAFLD patients (n = 656) used for a genome‐wide association study (GWAS).ResultsGLS, GCSH and ATP7B genes showed significant differences across the MAFLD spectrum and were significantly associated with liver fibrosis stages. GLS was closely associated with fibrosis stages in patients with MAFLD and those with MAFLD‐related HCC. GLS is predominantly expressed in monocytes and T cells in MAFLD. During the progression of metabolic dysfunction‐associated fatty liver to metabolic‐associated steatohepatitis, GLS expression in T cells decreased. GWAS revealed that multiple single nucleotide polymorphisms in GLS were associated with clinical indicators of MAFLD.ConclusionsGLS may contribute to liver inflammation and fibrosis in MAFLD mainly through cuprotosis and T‐cell activation, promoting the progression of MAFLD to HCC. These findings suggest that cuprotosis may play a role in MAFLD progression, potentially providing new insights into MAFLD pathogenesis.

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