Asian Journal of Surgery, Journal Year: 2025, Volume and Issue: unknown
Published: April 1, 2025
Language: Английский
Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)
Published: Nov. 3, 2023
Abstract Cardiovascular diseases pose a major threat worldwide. Common cardiovascular include acute myocardial infarction (AMI), heart failure, atrial fibrillation (AF) and atherosclerosis. Glycolysis process often has changed during these diseases. Lactate, the end-product of glycolysis, been overlooked in past but gradually identified to play biological functions recent years. Similarly, role lactate disease is being recognized. Targeting production, regulating transport, modulating circulating levels may serve as potential strategies for treatment future. The purpose this review integrate relevant clinical basic research on pathophysiological years clarify important guide further studies exploring other
Language: Английский
Citations
57
Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)
Published: Feb. 5, 2024
Abstract For decades, lactate has been considered a byproduct of glycolysis. The shuttle hypothesis shifted the paradigm, demonstrating that not only plays important roles in cellular metabolism but also communications, which can transcend compartment barriers and occur within among different cells, tissues organs. Recently, discovery induce novel post-translational modification, named lysine lactylation (Kla), brings forth new avenue to study nonmetabolic functions for lactate, inspired ‘gold rush’ academic commercial interest. Zhang et al. first showed Kla is manifested histones as epigenetic marks, then mounting evidences demonstrated occurs diverse non-histone proteins. widespread faithfully orchestrates numerous biological processes, such transcription, inflammatory responses. Notably, dysregulation touches myriad pathological processes. In this review, we comprehensively reviewed curated existing literature retrieve identified sites on both proteins summarized recent major advances toward its regulatory mechanism. We thoroughly investigated function underlying signaling pathway summarize how regulates various processes normal physiological states. addition, further highlight effects development human diseases including inflammation response, tumorigenesis, cardiovascular nervous system other complex diseases, might potentially contribute deeply understanding interpreting mechanism pathogenicity. Graphical
Language: Английский
Citations
37
International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(5), P. 1833 - 1854
Published: Jan. 1, 2024
The Warburg Effect is one of the most well-known cancer hallmarks.This metabolic pattern centered on lactate has extremely complex effects various aspects tumor microenvironment, including remodeling, immune suppression, cell migration, and drug resistance development.Based accumulating evidence, metabolites are likely to participate in regulation biological processes microenvironment form a feedback loop.Therefore, further revealing key mechanism lactate-mediated oncological reasonable scientific idea.The discovery refinement histone lactylation recent years laid firm foundation for above idea.Histone post-translational modification that occurs at lysine sites histones.Specific enzymes, known as "writers" "erasers", catalyze addition or removal, respectively, lactacyl group target sites.An increasing number investigations have reported this multiple cellular procedures.In review, we discuss close connection between series tumorigenesis, infiltration, energy metabolism.Finally, review provides insightful perspectives, identifying promising avenues exploration potential clinical application field research.
Language: Английский
Citations
29
Advanced Science, Journal Year: 2024, Volume and Issue: 11(19)
Published: March 17, 2024
Abstract Activated microglia in the retina are essential for development of autoimmune uveitis. Yin‐Yang 1 (YY1) is an important transcription factor that participates multiple inflammatory and immune‐mediated diseases. Here, increased YY1 lactylation retinal within experimental uveitis (EAU) group observed. contributed to boosting microglial activation promoting their proliferation migration abilities. Inhibition suppressed attenuated inflammation EAU. Mechanistically, cleavage under targets & tagmentation （CUT&Tag） analysis revealed promoted by regulating a set genes, including STAT3, CCL5, IRF1, IDO1 , SEMA4D . In addition, p300 identified as writer lactylation. decreased vivo vitro. Collectively, results showed dysfunction upregulating cytokine secretion cell proliferation. Therapeutic effects can be achieved targeting lactate/p300/YY1 lactylation/inflammatory genes axis.
Language: Английский
Citations
29
Circulation Research, Journal Year: 2024, Volume and Issue: 134(11), P. 1427 - 1447
Published: April 17, 2024
Medial arterial calcification is a chronic systemic vascular disorder distinct from atherosclerosis and commonly observed in patients with kidney disease, diabetes, aging individuals. We previously showed that NR4A3 (nuclear receptor subfamily 4 group A member 3), an orphan nuclear receptor, key regulator apo (apolipoprotein) A-IV-induced progression; however, its role poorly understood.
Language: Английский
Citations
28
Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)
Published: Jan. 10, 2024
As more is learned about lactate, it acts as both a product and substrate functions shuttle system between different cell populations to provide the energy for sustaining tumor growth proliferation. Recent discoveries of protein lactylation modification mediated by lactate play an increasingly significant role in human health (e.g., neural osteogenic differentiation maturation) diseases tumors, fibrosis inflammation, etc.). These views are critically first described detail this review. Hence, here, we focused on new target, lactylation, which may be "double-edged sword" diseases. The main purpose review was describe how multiple physiological pathological processes their potential mechanisms through in-depth summary preclinical vitro vivo studies. Our work aims ideas treating accelerate translation from bench bedside.
Language: Английский
Citations
20
Theranostics, Journal Year: 2025, Volume and Issue: 15(5), P. 1787 - 1821
Published: Jan. 2, 2025
Lactate is an indispensable substance in various cellular physiological functions and plays regulatory roles different aspects of energy metabolism signal transduction. Lactylation (Kla), a key pathway through which lactate exerts its functions, has been identified as novel posttranslational modification (PTM). Research indicates that Kla essential balancing mechanism variety organisms involved many biological processes pathways. closely related to disease development represents potential important new drug target. In line with existing reports, we searched for newly discovered sites on histone nonhistone proteins; reviewed the mechanisms (particularly focusing enzymes directly reversible regulation Kla, including "writers" (modifying enzymes), "readers" (modification-binding "erasers" (demodifying enzymes); summarized crosstalk between PTMs help researchers better understand widespread distribution diverse functions. Furthermore, considering "double-edged sword" role both pathological contexts, this review highlights "beneficial" states (energy metabolism, inflammatory responses, cell fate determination, development, etc.) "detrimental" pathogenic or inducive effects processes, particularly malignant tumors complex nontumor diseases. We also clarify molecular health disease, discuss feasibility therapeutic Finally, describe detection technologies their applications diagnosis clinical settings, aiming provide insights treatment diseases accelerate translation from laboratory research practice.
Language: Английский
Citations
2
Advanced Science, Journal Year: 2023, Volume and Issue: 10(31)
Published: Sept. 26, 2023
Abstract Blood vessels play a role in osteogenesis and osteoporosis; however, the of vascular metabolism these processes remains unclear. The present study finds that ovariectomized mice exhibit reduced blood vessel density bone expression endothelial glycolytic regulator pyruvate kinase M2 (PKM2). Endothelial cell (EC)‐specific deletion Pkm2 impairs worsens osteoporosis mice. This is attributed to impaired ability mesenchymal stem cells (BMSCs) differentiate into osteoblasts. Mechanistically, EC‐specific reduces serum lactate levels secreted by ECs, which affect histone lactylation BMSCs. Using joint CUT&Tag RNA sequencing analyses, collagen type I alpha 2 chain (COL1A2), cartilage oligomeric matrix protein (COMP), ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), transcription factor 7 like (TCF7L2) as osteogenic genes regulated H3K18la are identified. PKM2 overexpression addition, exercise restore phenotype PKM2‐deficient Furthermore, metabolomics indicate patients with have relatively low levels. Additionally, related BMSCs downregulated osteoporosis. In conclusion, glycolysis ECs fuels BMSC differentiation osteoblasts through lactylation, partially ameliorates increasing
Language: Английский
Citations
40
Metabolic Brain Disease, Journal Year: 2023, Volume and Issue: 38(5), P. 1543 - 1553
Published: March 4, 2023
Language: Английский
Citations
34
Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(22)
Published: Nov. 14, 2024
Glioblastoma (GBM), an aggressive brain malignancy with a cellular hierarchy dominated by GBM stem cells (GSCs), evades antitumor immunity through mechanisms that remain incompletely understood. Like most cancers, GBMs undergo metabolic reprogramming toward glycolysis to generate lactate. Here, we show lactate production patient-derived GSCs and microglia/macrophages induces tumor cell epigenetic histone lactylation, activating modification leads immunosuppressive transcriptional programs suppression of phagocytosis via upregulation CD47, "don't eat me" signal, in cells. Leveraging these findings, pharmacologic targeting augments efficacy anti-CD47 therapy. Mechanistically, lactylated interacts the heterochromatin component chromobox protein homolog 3 (CBX3). Although CBX3 does not possess direct lactyltransferase activity, binds acetyltransferase (HAT) EP300 induce increased substrate specificity lactyl-CoA shift cytokine profile. Targeting inhibits growth both cell–intrinsic phagocytosis. Collectively, results suggest mediates metabolism-induced contributes CD47-dependent immune evasion, which can be leveraged augment immuno-oncology therapies.
Language: Английский
Citations
13