The lactate dehydrogenase (LDH) isoenzyme spectrum enables optimally controlling T cell glycolysis and differentiation

Chen, Xuyong; Liu, Lingling; Kang, Siwen; Gnanaprakasam, JN Rashida; Wang, Ruoning

doi:10.1126/sciadv.add9554

Cited by 14 publications

(8 citation statements)

References 43 publications

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“…Compared with the drastically decreased RocF activity, ArgG seemed to retain most of its activity, which seems to imply that the isofunctional enzymes of ArgG may be present in Bt. Organisms often have multiple replacement genes or proteins for important enzymes or proteins 27 In fact, according to the GO annotations of genome sequencing in our previous work, 25,26 two presumptive isofunctional genes (BSP001038 and BSP001049) were detected in Bt LLP29. In addition, because ArgG is a ratelimiting enzyme for arginine synthesis, its expression level is usually very low.…”

Section: Discussionmentioning

confidence: 96%

Urea Cycle of Bacillus thuringiensis Affects Its Survival under UV Stress

Zhang,

Chen,

et al. 2024

J. Agric. Food Chem.

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Bacillus thuringiensis (Bt) is widely used to produce biological pesticides. However, its persistence is limited because of ultraviolet (UV) rays. In our previous study, we found that exogenous intermediates of the urea cycle were beneficial to Bt for survival under UV stress. To further explore the effect of the urea cycle on the resistance mechanism of Bt, the rocF/argG gene, encoding arginase and argininosuccinate synthase, respectively, were knocked out and recovered in this study. After the target genes were removed, respectively, the urea cycle in the tested Bt was inhibited to varying degrees. The UV stress test showed that the urea cycle disorder could reduce the resistance of Bt under UV stress. Meanwhile, the antioxidant enzyme activities of Bt were also decreased to varying degrees due to the knockout of the target genes. All of these results revealed that the urea cycle can metabolically regulate the stress resistance of Bt.

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Section: Discussionmentioning

confidence: 96%

Urea Cycle of Bacillus thuringiensis Affects Its Survival under UV Stress

Zhang,

Chen,

et al. 2024

J. Agric. Food Chem.

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“…Down-regulation of LDHB expression disrupts lactate-to-pyruvate conversion, leading to impaired mitochondrial ATP production and inhibition of oxidative phosphorylation. Overexpression of LDHB in mouse muscle enhances mitochondrial gene expression and respiratory capacity [59,60]. MLC1, also known as astrocyte membrane protein 1, played a crucial role in cerebral neurovascular development and physiology [61,62].…”

Section: Discussionmentioning

confidence: 99%

Study on the Characteristics of Coarse Feeding Tolerance of Ding’an Pigs: Phenotypic and Candidate Genes Identification

Song,

Xue,

Wang

et al. 2024

Genes

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Ding’an (DA) pig, a prominent local breed in Hainan Province, exhibits notable advantages in coarse feeding tolerance and high-quality meat. To explore the potential genetic mechanism of coarse feeding tolerance in DA pigs, 60-day-old full sibling pairs of DA and DLY (Duroc-Landrace-Yorkshire) pigs were subjected to fed normal (5%) and high (10%) crude fiber diets for 56 days, respectively. The findings showed that increasing the crude fiber level had no impact on the apparent digestibility of crude fiber, intramuscular fat, and marbling scores in DA pigs, whereas these factors were significantly reduced in DLY pigs (p < 0.05). Through differential expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) of the colonic mucosal transcriptome data, 65 and 482 candidate genes with coarse feeding tolerance in DA pigs were identified, respectively. Joint analysis screened four key candidate genes, including LDHB, MLC1, LSG1, and ESM1, potentially serving as key regulated genes for coarse feeding tolerance. Functional analysis revealed that the most significant pathway enriched in differential genes associated with coarse feeding tolerance in Ding’an pigs was the signaling receptor binding. The results hold substantial significance for advancing our understanding of the genetic mechanisms governing coarse feeding tolerance in Ding’an pigs.

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“…Lactate dehydrogenase (LDH) isozymes are tetramer of the translation products of the LDHA and LDHB genes. Chen et al [26] found that deletion of LDHA inhibited glycolysis, cell proliferation and differentiation, whereas deletion of LDHB promoted glycolysis but inhibited T-cell differentiation. In CD8+ effector T cells, the glycolytic enzyme lactate dehydrogenase A (LDHA) is induced by phosphoinositide 3-kinase (PI3K) signaling, and ablation of LDHA inhibits protein kinase B (AKT) and forkhead box 1 (Foxo1) activity, leading to decreased T cell effector function.…”

Section: Glucosementioning

confidence: 99%

Targeting metabolism to improve CAR-T cells therapeutic efficacy

Liu,

Zhao,

Gao

et al. 2024

Chinese Medical Journal

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Chimeric antigen receptor T (CAR-T) cell therapy achieved advanced progress in the treatment of hematological tumors. However, the application of CAR-T cell therapy for solid tumors still faces many challenges. Competition with tumor cells for metabolic resources in an already nutrient-poor tumor microenvironment is a major contributing cause to CAR-T cell therapy’s low effectiveness. Abnormal metabolic processes are now acknowledged to shape the tumor microenvironment, which is characterized by increased interstitial fluid pressure, low pH level, hypoxia, accumulation of immunosuppressive metabolites, and mitochondrial dysfunction. These factors are important contributors to restriction of T cell proliferation, cytokine release, and suppression of tumor cell-killing ability. This review provides an overview of how different metabolites regulate T cell activity, analyzes the current dilemmas, and proposes key strategies to reestablish the CAR-T cell therapy’s effectiveness through targeting metabolism, with the aim of providing new strategies to surmount the obstacle in the way of solid tumor CAR-T cell treatment.

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The lactate dehydrogenase (LDH) isoenzyme spectrum enables optimally controlling T cell glycolysis and differentiation

Cited by 14 publications

References 43 publications

Urea Cycle of Bacillus thuringiensis Affects Its Survival under UV Stress

Urea Cycle of Bacillus thuringiensis Affects Its Survival under UV Stress

Study on the Characteristics of Coarse Feeding Tolerance of Ding’an Pigs: Phenotypic and Candidate Genes Identification

Targeting metabolism to improve CAR-T cells therapeutic efficacy

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