Downregulation of Gldc attenuates myocardial ischemia reperfusion injury in vitro by modulating Akt and NF-κB signalings.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39747134", "kind": "science-record", "revision": 4, "content_hash": "sha256:b2b4ad8213ec15e6b413bf51b8fa248c93a03db64a09fa1a700f1006dc913361", "created_at": "2026-11-01T20:30:04Z", "updated_at": "2026-11-01T22:55:56Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Downregulation of Gldc attenuates myocardial ischemia reperfusion injury in vitro by modulating Akt and NF-κB signalings.", "doi": "10.1038/s41598-024-79445-5", "pmid": "39747134", "authors": ["Lian Shuang", "Youle Su", "Yue Zhang"], "journal": "Scientific reports", "year": 2025, "abstract": "Myocardial ischemia/reperfusion injury (MIRI) is a serious clinical complication that is caused by reperfusion therapy following myocardial infarction (MI). Mitochondria-related genes (Mito-RGs) play important roles in multiple diseases. However, the role of mitochondria-related genes in MIRI remains largely unknown. The GSE67308 dataset from the GEO database was utilized to identify MIRI-related gene modules through WGCNA. Meanwhile, differential expression analysis was conducted to identify differentially expressed genes (DEGs) in the GSE61592 dataset. Next, candidate Mito-RGs related to MIRI were screened by Venn analysis. Thereafter, a myocardial hypoxia/reperfusion (H/R) H9C2 cell model and a mouse ischemia/reperfusion (I/R) model were established to verify the expression level of glycine decarboxylase (Gldc) in MIRI in vitro and in vivo. Based on data from the GEO database, Gldc levels were notably upregulated in murine MIRI samples, compared to the control group. RT-qPCR and western blot confirmed that Gldc levels were obviously elevated in the heart of I/R mice and H/R-exposed cardiomyocytes. Moreover, the deficiency of Gldc notably increased the viability and reduced the apoptosis and inflammatory responses in H9C2 cells exposed to H/R. Meanwhile, Gldc downregulation significantly reduced p-NF-κB p65, Bax and cleaved caspase 3 levels and elevated p-Akt and Bcl-2 levels in H9C2 cells exposed to H/R. The ROC curve analysis further demonstrated that Gldc gene exhibited good diagnostic value for MIRI. Collectively, Gldc deficiency could attenuate H/R injury in cardiomyocytes in vitro through activating Akt and inactivating NF-κB signalings. These data suggested that GLDC may serve as both a diagnostic and therapeutic target for MIRI.", "claims": [{"id": "claim-method", "statement": "The “WGCNA” package in R language was utilized to screen key modules24. The data from the GSE61592 dataset were analyzed for screening differential expressed genes (DEGs). The DEGs were identified by the “limma” package (version 3.52.4) in R language with |log2FC| > 0.5 and FDR < 0.05 as screening threshold25.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39747134", "locator": "sections[4] \"Weighted gene co-expression network analysis (WGCNA)\" paragraph 2", "quote": "The “WGCNA” package in R language was utilized to screen key modules24."}, {"asset": "source:pmid:39747134", "locator": "sections[5] \"Differential expression analysis\" paragraph 2", "quote": "The data from the GSE61592 dataset were analyzed for screening differential expressed genes (DEGs)."}, {"asset": "source:pmid:39747134", "locator": "sections[5] \"Differential expression analysis\" paragraph 2", "quote": "The DEGs were identified by the “limma” package (version 3.52.4) in R language with |log2FC| > 0.5 and FDR < 0.05 as screening threshold25."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets (GSE61592, GSE67308, GSE130217, GSE97320 and GSE66360) used and analysed during the current study are available in the Gene Expression Omnibus (GEO) database [http://www.ncbi.nlm.nih.gov/geo/].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39747134", "locator": "sections[35] \"notes\" paragraph 1", "quote": "The datasets (GSE61592, GSE67308, GSE130217, GSE97320 and GSE66360) used and analysed during the current study are available in the Gene Expression Omnibus (GEO) database [http://www.ncbi.nlm.nih.gov/geo/]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The overlap among the 2377 MIRI-related genes, 4139 DEGs and 1140 Mito-RGs was assessed using a Venn diagram, resulting in the identification of 11 hub genes including Coq10a, Mrpl55, Bdh1, Gldc, Mthfd2, Alas2, Bcat2, Slc25a45, Ucp3, Cbr3 and Armcx1 (Fig. 1E and Table S2).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39747134", "locator": "sections[22] \"Identification of candidate Mito-RGs associated with MIRI\" paragraph 4", "quote": "The overlap among the 2377 MIRI-related genes, 4139 DEGs and 1140 Mito-RGs was assessed using a Venn diagram, resulting in the identification of 11 hub genes including Coq10a, Mrpl55, Bdh1, Gldc, Mthfd2, Alas2, Bcat2, Slc25a45, Ucp3, Cbr3 and Armcx1 (Fig. 1E and Table S2)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The overlap among the 2377 MIRI-related genes, 4139 DEGs and 1140 Mito-RGs was assessed using a Venn diagram, resulting in the identification of 11 hub genes including Coq10a, Mrpl55, Bdh1, Gldc, Mthfd2, Alas2, Bcat2, Slc25a45, Ucp3, Cbr3 and Armcx1 (Fig. 1E and Table S2).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:39747134"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Based on data from the GEO database, Gldc l", "tabase, Gldc levels were notably upregulated in murine MIRI samples, compared to the control group.", "oxia/reperfusion (H/R) H9C2 cell model and a mouse ischemia/reperfusion (I/R) model were establ"], "order_basis": "paper_text_order:784", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["MIRI samples, compared to the control group. RT-qPCR and western blot confirmed that Gldc levels", "I samples, compared to the control group. RT-qPCR and western blot confirmed that Gldc levels"], "order_basis": "paper_text_order:1062", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": [", compared to the control group. RT-qPCR and western blot confirmed that Gldc levels were obviously el"], "order_basis": "paper_text_order:1074", "id": "assay:3"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ably increased the viability and reduced the apoptosis and inflammatory responses in H9C2 cells exp", "icantly reduced p-NF-κB p65, Bax and cleaved caspase 3 levels and elevated p-Akt and Bcl-2 levels"], "order_basis": "paper_text_order:1276", "id": "assay:4"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Materials and methods Cell culture, transfection and treatment H9C2 cells (Procell) were cult", "Co., LTD). Approximately 105 H9C2 cells were transfected with 50 pmol of siRNA negative control, Gldc", "cells, Gldc specific small interfering RNA (siRNA) sequences were purchased from (GUIJI Biotec", "H9C2 cells were transfected with 50 pmol of siRNA negative control, Gldc siRNA1 or Gldc siRNA2"], "order_basis": "paper_text_order:1891", "id": "assay:5"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["tion and treatment H9C2 cells (Procell) were cultured in high-glucose DMEM supplemented with 10% FBS", "ation (H/R) injury in vitro, H9C2 cells were cultured in DMEM without glucose and serum and maintaine", "CO2) at 37 °C for 4 h. Next, cells were then cultured in complete DMEM containing glucose and serum a"], "order_basis": "paper_text_order:1935", "id": "assay:6"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The “WGCNA” package in R language was utilized to screen key modules24. The data from the GSE61592 dataset were analyzed for screening differential expressed genes (DEGs). The DEGs were identified by the “limma” package (version 3.52.4) in R language with |log2FC| > 0.5 and FDR < 0.05 as screening threshold25."], "order_basis": "consumes_earlier_output", "id": "assay:7"}]}