Global-Scale Profiling of Differential Expressed Lysine-Lactylated Proteins in the Cerebral Endothelium of Cerebral Ischemia–Reperfusion Injury Rats

Yao, Yuan; Bade, Rengui; Li, Guotao; Zhang, Aoqi; Zhao, Haile; Fan, Lifei; Zhu, Runxiu; Yuan, Jun

doi:10.1007/s10571-022-01277-6

Cited by 18 publications

(21 citation statements)

References 52 publications

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“…A subcellular localization analysis of the 333 lactylated proteins was conducted by using UniProt database notes. As shown in Figure 3A, most of the lactylated proteins in human lungs were distributed in the cytoplasm (29.8%) and nucleus (29.1%), which is the same as the three subcellular localizations with the most lactylated proteins in human gastric cancer cells and other cell types [14–19]. In addition, our analysis revealed that secreted proteins, proteins associated with chromosomes, proteins in the extracellular space and at other locations were lactylated, demonstrating that the lactylation profile of human lungs shows diverse subcellular distributions (Figure 3A).…”

Section: Resultssupporting

confidence: 66%

“…However, it is interesting that the proline (P) residue was found to be enriched in the second position upstream of the Kla site in AGS human gastric cancer cells [11], while in our motifs, it was enriched in the third position downstream of the Kla site. We did not find any same enriched residues in the motifs of other species [15–19], which suggested that lactylated proteins exhibit a specific preference for substrates in different human tissue or cell lines, and the differences among species were great.…”

Section: Resultsmentioning

confidence: 88%

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Global profiling of lysine lactylation in human lungs

Yang,

Wang,

Kong

et al. 2023

Proteomics

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Lactate is closely related to various cellular processes, such as angiogenesis, responses to hypoxia, and macrophage polarization, while regulating natural immune signaling pathways and promoting neurogenesis and cognitive function. Lysine lactylation (Kla) is a novel posttranslational modification, the examination of which may lead to new understanding of the nonmetabolic functions of lactate and the various physiological and pathological processes in which lactate is involved, such as infection, tumorigenesis and tumor development. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), researchers have identified lactylation in human gastric cancer cells and some other species, but no research on lactylation in human lungs has been reported.In this study, we performed global profiling of lactylation in human lungs under normal physiological conditions, and 724 Kla sites in 451 proteins were identified. After comparing the identified proteins with those reported in human lactylation datasets, 141 proteins that undergo lactylation were identified for the first time in this study.Our work expands the database on human lactylation and helps advance the study on lactylation function and regulation under physiological and pathological conditions.

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Section: Resultssupporting

confidence: 66%

Section: Resultsmentioning

confidence: 88%

Global profiling of lysine lactylation in human lungs

Yang,

Wang,

Kong

et al. 2023

Proteomics

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“…The role of Kla in cerebral ischemia–reperfusion injury (CIRI) has been elucidated recently. Extensive Kla modifications were identified on proteins from cortical proteins of a CIRI rat, and most of the Kla modified proteins mediate neuronal apoptosis by their involvement in Ca 2+ signaling pathways (Yao et al., 2022). In addition to antibody‐based immunoprecipitation coupled with MS on proteomic studies, the bioorthogonal chemical reporter strategy has emerged as a powerful method for studying protein PTMs (Grammel & Hang, 2013; Parker & Pratt, 2020; Prescher & Bertozzi, 2005).…”

Section: Overview Of New Lysine Acylation Biomarkersmentioning

confidence: 99%

New Histone Lysine Acylation Biomarkers and Their Roles in Epigenetic Regulation

Cat

Zheng

2023

Current Protocols

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Protein posttranslational modification (PTM) is a biochemical mechanism benefitting cellular adaptation to dynamic intracellular and environmental conditions. Recently, several acylation marks have been identified as new protein PTMs occurring on specific lysine residues in mammalian cells: isobutyrylation, methacrylation, benzoylation, isonicotinylation, and lactylation. These acylation marks were initially discovered to occur on nucleosomal histones, but they potentially occur as prevalent biomarkers on non-histone proteins as well. The existence of these PTMs is a downstream consequence of metabolism and demonstrates the intimate crosstalk between active cellular metabolites and regulation of protein function. Emerging evidence indicates that these acylation marks on histones affect DNA transcription and are functionally distinct from the well-studied lysine acetylation. Herein, we discuss enzymatic regulation and metabolic etiology of these acylations, 'reader' proteins that recognize different acylations, and their possible physiological and pathological functions. Several of these modifications correlate with other well-studied acylations and fine-tune the regulation of gene expression. Overall, findings of these acylation marks reveal new molecular links between metabolism and epigenetics and open up many questions for future investigation.

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“…The results were validated in an oxygen-glucose deprivation cell model. [38] Through lysine-lactylation proteomics analysis on rat cerebral after ischemia followed by reperfusion, Yao et al [39] identified 1003 lactylation sites on 469 proteins, including 54 upregulated and 54 downregulated lysine-lactylation sites (vs controls) from 49 and 99 proteins, respectively. The authors further validated altered lactylation on the important Ca 2+ signaling proteins (Scl25a4, Slc25a5, Vdac1, and Vdac2) and proposed lactylation involvement in the underlying mechanism of cerebral ischemia–reperfusion injury via mediating mitochondrial apoptosis and neuronal death.…”

Section: Proteomics Studies Of Acute Ischemic Stroke In Animal Modelsmentioning

confidence: 99%

“…The authors further validated altered lactylation on the important Ca 2+ signaling proteins (Scl25a4, Slc25a5, Vdac1, and Vdac2) and proposed lactylation involvement in the underlying mechanism of cerebral ischemia–reperfusion injury via mediating mitochondrial apoptosis and neuronal death. [39] Using targeted proteomics, molecular mechanisms that drive the brain-lung interaction poststroke were studied in a MCAO mouse model. A 92 multiplex protein panel developed by Olink Proteomics® was used to analyze the content in bronchoalveolar lavage fluid and lung homogenates, Hgf, Tgf-α, and Ccl2 were identified and further validated by the enzyme-linked immunosorbent assay as dysregulated proteins in the lungs after cerebral ischemia, suggesting a potential important role in stroke-induced lung damage.…”

Section: Proteomics Studies Of Acute Ischemic Stroke In Animal Modelsmentioning

confidence: 99%

Proteomic investigations of acute ischemic stroke in animal models: a narrative review

Sun

Wei

2022

J Bio-X Res

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Acute ischemic stroke (AIS), a neurological injury resulting from blood clots, is the second most common cause of death worldwide. Novel therapeutics are urgently needed. Rapid developments in instrumentation and bioinformatics have resulted in increased use of mass spectrometry-based proteomics as an effective tool for the in-depth study of AIS. This review focuses on proteomics investigations of AIS in animal models. We highlight the study findings in system-wide protein abundance changes and molecular mechanisms underlying AIS with or without therapeutic intervention, as well as prestroke prognosis investigations. This review reveals that common molecular pathways related to ischemic injury and spontaneous recovery have been uncovered and part of AIS-changed proteins have been repeatedly identified, indicating the promise of proteomics in generating novel therapeutic targets and biomarker candidates. We also discuss challenges, alleviating strategies, and perspectives of mass spectrometrybased proteomics in AIS research and call for a broad application of systems-level investigations on preclinical AIS molecular mechanism elucidation, target discovery and validation, and therapeutics development.

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Global-Scale Profiling of Differential Expressed Lysine-Lactylated Proteins in the Cerebral Endothelium of Cerebral Ischemia–Reperfusion Injury Rats

Cited by 18 publications

References 52 publications

Global profiling of lysine lactylation in human lungs

Global profiling of lysine lactylation in human lungs

New Histone Lysine Acylation Biomarkers and Their Roles in Epigenetic Regulation

Proteomic investigations of acute ischemic stroke in animal models: a narrative review

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