LANCL1

更新于：2025-05-07

基本信息

别名

40 kDa erythrocyte membrane protein、Glutathione S-transferase LANCL1、GPR69A

+ [4]

简介

Functions as a glutathione transferase. Catalyzes conjugation of the glutathione (GSH) to artificial substrates 1-chloro-2,4-dinitrobenzene (CDNB) and p-nitrophenyl acetate. Mitigates neuronal oxidative stress during normal postnatal development and in response to oxidative stresses probably through GSH antioxidant defense mechanism (By similarity). May play a role in EPS8 signaling. Binds glutathione (PubMed:19528316).

关联

项与 LANCL1 相关的药物

US20230348622

专利挖掘

靶点

LANCL1

作用机制-

在研机构

香港大学

原研机构

香港大学

在研适应症

肿瘤

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 LANCL1 相关的临床结果

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100 项与 LANCL1 相关的转化医学

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0 项与 LANCL1 相关的专利（医药）

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项与 LANCL1 相关的文献（医药）

2025-04-01·Journal of Dairy Science

Omega-3 fatty acid supplementation from late pregnancy to early lactation attenuates the endocannabinoid system and immune proteome in preovulatory follicles and endometrium of Holstein dairy cows

Article

作者: Levin, Y ; Itkin, M ; Zachut, M ; Dos S Silva, P ; Kra, G ; Moallem, U ; Malitsky, S ; Butenko, Y

Activation of the endocannabinoid system (ECS) elicits negative effects on the reproductive system in mammals. Supplementation with n-3 fatty acid (FA) lowers ECS activation and has anti-inflammatory effects. Thus, we hypothesized that supplementing cows with n-3 FA will downregulate components of the ECS and immune system in preovulatory follicles and in the endometrium. Twenty-four multiparous Holstein dairy cows were supplemented from d 256 of pregnancy to d 70 postpartum as follows: (1) control (CTL; n = 12), prepartum with 250 g/d per cow calcium salts of FA and postpartum at 1.6% of the diet (DM basis); or (2) extruded flaxseed (FLX; n = 12) supplement rich in α-linolenic acid (C18:3n-3), prepartum with 700 g/d per cow and postpartum at 6.4% of diet (DM basis). Ovaries were monitored at 30 DIM, and following estrous cycle synchronization we aspirated the follicular fluids (FF) of follicles ≥7 mm, separated the granulosa cells (GRC), and performed endometrium biopsies at 58 ± 5 DIM. The FF were analyzed for concentrations of estradiol (E₂) and progesterone (P₄), and E₂-active follicles were declared when E₂/P₄ was >1. The FA and endocannabinoid (eCB) profiles were determined in plasma and in the reproductive tissues. Proteomic analyses and mRNA abundances were determined in GRC and endometrium. Supplementation of n-3 FA increased the proportion of total n-3 FA and decreased the ratio of n-6 to n-3 ratio in plasma, FF and GRC compared with CTL. In plasma and FF, n-3 FA supplementation decreased the proportion of the n-6 FA eCB precursor arachidonic acid (ARA; C20:4n-6), and increased the abundance of the n-3 FA-derived eCB eicosapentaenoyl ethanolamide compared with CTL. In the endometrium, n-3 FA supplementation reduced the abundance of the n-6 FA-derived eCB 2-arachidonoylglycerol (2-AG) compared with CTL. Proteomic analysis of GRC showed that n-3 FA supplementation increased the abundance of FA-binding-protein-5, which is involved in intracellular transport of eCB, as well as the abundances of the cytokine receptor like factor-2 and glutathione-S-transferase-LANCL1, whereas it reduced the abundances of several complement proteins: complement factors I, D, H, complement components C7 chain and C8 β chain, and complement component 1 Q subcomponent-binding protein, mitochondrial (C1QBP). In addition, the abundance of superoxide dismutase (SOD3) was lower in FLX GRC than in CTL. In the endometrium, n-3 FA supplementation decreased the abundance of a few immune-related proteins. In the GRC, n-3 FA supplementation reduced the relative mRNA abundances of cannabinoid receptors 1 and 2 compared with CTL. Across treatments, a positive correlation was found between the relative abundance in FF of the eCB anandamide with C7, C1QBP, and SOD3 in GRC, whereas FF 2-AG had a negative correlation with them. Overall, in line with our premise, dietary n-3 FA supplementation attenuated the levels of some eCB and reduced the expression of several proteins and genes related to the ECS and immune system in the preovulatory follicle and in the endometrium, which may be part of the etiology of the positive effects of n-3 FA on the reproductive system in dairy cows.

2025-04-01·Neuroscience

Discovering genetically-supported drug targets for multisite chronic pain through multi-omics Mendelian randomization and single-cell RNA-sequencing

Article

作者: Lin, Liling ; Qiu, Junxiong ; Lin, Jianwei ; Fu, Yanni ; Cui, Ziyang

Multisite chronic pain (MCP) is a highly prevalent disorder with substantial unmet therapeutic needs.We conducted multi-omics Mendelian randomization and Bayesian colocalization to identify potential therapeutic targets for MCP. Summary-level data of gene expressions and protein abundance levels were obtained from corresponding quantitative trait loci studies, respectively. Summary-level data for MCP was leveraged from the UK Biobank. The transcriptome-wide association study (TWAS), Mendelian randomization, and Bayesian colocalization approaches were applied to investigate the potential causal effects of gene expressions and protein levels on MCP in both blood and brain tissues. Phenome-wide Mendelian randomization analysis (MR-PheWAS), single-cell sequencing data, protein-protein interaction (PPI), and reaction pathway analysis were further conducted to digging the underlying mechanisms. Our analysis identified and validated two plasma targets for MCP, namely KLC1 and LANCL1, at both gene expression levels and protein levels across multi-methodologies. Moreover, MR-PheWAS observed additional benefits associated with these two targets. Through analyses based on single-cell sequencing data, we identified critical cell types for KLC1, primarily megakaryocytes, and neurons, notably linked to the axon guidance pathway, while LANCL1 showed associations with B lymphocytes, neurons, and the electron transport pathway. In dorsal root ganglions, we identified enrichments of both LANCL1 and KLC1 in putative silent nociceptors. The effects are possibly mediated through axonal transport and the activation of NMDARs, supported by PPI and reaction pathway analysis. Our multi-dimensional analysis suggests that genetically determined KLC1 and LANCL1 are causally linked to MCP risk, holding promise as appealing drug targets for MCP.

2025-04-01·Experimental Neurology

Corrigendum to “LanCL1 protects developing neurons from long-term isoflurane anesthesia-induced neurotoxicity” [Experimental Neurology 381 (2024) 114880]