Global-scale profiling of differential expressed lysine-lactylated proteins in the cerebral endothelium of cerebral ischemia-reperfusion injury rats
Open accessAbstract
Acute ischemic stroke (AIS) is a serious threat to human health. Following AIS, cerebral ischemia-reperfusion injury (CIRI) must be treated to improve prognosis. By combining 4D label-free quantitative proteomics with lactylation modification-specific proteomics analysis, we assessed lysine lactylation (Kla) in cortical proteins of a CIRI rat model. We identified a total of 1003 lactylation sites on 469 proteins in this study, gathering quantitative information (PXD034232) on 660 of 310 proteins, which were further classified by cell composition, molecular function, and biological processes. In addition, we analyzed the metabolic pathways, domains, and protein-protein interaction networks. Lastly, we evaluated differentially expressed lysine lactylation sites, determining 49 upregulated proteins and 99 downregulated proteins with 54 upregulated sites and 54 downregulated sites in the experimental group in comparison with the healthy control group. Moreover, we identified the Kla of Scl25a4 and Slc25a5 in the Ca 2+ signaling pathway, but the Kla of Vdac1 was eliminated, as confirmed in vivo. Overall, these results provide new insights into lactylation involved in the underlying mechanism of CIRI because this post-translational modification affects the mitochondrial apoptosis pathway and mediates neuronal death. Therefore, this study may enable us to develop new molecules with therapeutic properties, which have both theoretical significance and broad clinical application prospects. A new model of cerebral ischemia-reperfusion injury (CIRI) induced by lactylation through the regulation of key proteins of the Ca 2+ signaling pathway.
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Lactate-associated lactylation modulates glial inflammatory states and neuronal synaptic function, supporting its role in neuroplasticity.
“Recent findings indicate that lactate-associated lactylation modulates glial inflammatory states and neuronal synaptic function, supporting its role in neuroplasticity (Yao et al., 2023; Hagihara et al., 2021).”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Yao et al., 2023
The Discussion (page unavailable) links lactate to neuronal excitability and plasticity, and proposes that lactylation of neuronal proteins may affect apoptosis after ischemia–reperfusion. It does not show that lactylation modulates neuronal synaptic function or glial inflammatory states; its discussion of astrocytes concerns lactate production, not inflammation. (LLM, conf=0.82)
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References 52 · Cited by 86
Research works printed but not linked: 5
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- Authors
- Yao, Y., Bade, R., Li, G., Zhang, A., Zhao, H., Fan, L., Zhu, R., & Yuan, J.
- Affiliations
- Inner Mongolia University (CN)
- Baotou Medical College (CN)
- Corresponding author
- Yao, Yuan
- Zhu, Runxiu
- Yuan, Jun
- Venue
- Cellular and Molecular Neurobiology
- Published
- 2022-08-27
- Volume
- 43
- Issue
- 5
- Pages
- 1989-2004
- ISSN
- 0272-4340 (ISSN-L)
- 1573-6830
- PMC
- PMC11412193
- OpenAlex
- W4293335078
- Cited by
- 86
- References
- 52
- Citations by year
- 2026: 19 · 2025: 38 · 2024: 19 · 2023: 9 · 2022: 1
- FWCI
- 6.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Cellular and Molecular Neurobiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Science and Technology Major Project of Inner Mongolia (2022YFSH0133, 2021GG0123)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Physical Sciences › Chemistry › Organic Chemistry › Click Chemistry and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- lysine lactylation, cerebral ischemia-reperfusion injury, acute ischemic stroke, brain endothelium, cortical proteins, differentially expressed proteins, SLC25A5, VDAC1, calcium signaling, mitochondrial apoptosis, neuronal cell death, post-translational modification
- MeSH terms
- Ischemic Stroke, Animals, Brain Ischemia, Humans, Lysine, Reperfusion Injury, Rats, Sprague-Dawley, Rats
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