Lactylation in health and disease: physiological or pathological?

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

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Unlocking the multifaceted molecular functions and diverse disease implications of lactylation

Biological reviews/Biological reviews of the Cambridge Philosophical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 16, 2024

ABSTRACT In recent years, a significant breakthrough has emerged in biology, the identification of lactylation, novel post‐translational process. This intriguing modification is not limited to specific class proteins but occurs across diverse range, including histones, signalling molecules, enzymes, and substrates. It can exert broad regulatory role various diseases, ranging from developmental anomalies neurodegenerative disorders inflammation cancer. Thus, it presents exciting opportunities for exploring innovative treatment approaches. As result, there been surge research interest, leading deeper understanding molecular mechanisms functions underlying lactylation within physiological pathological processes. Here, we review detection biological disease effects, providing systematic overview this modification.

Language: Английский

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Lactate and Lactylation in Sepsis: A Comprehensive Review

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 4405 - 4417

Published: July 1, 2024

Sepsis is a disorder of the immune response to infection or infectious factors with high morbidity and mortality in clinical settings. The lactylation lysine residues, fueled by lactate, plays pivotal role its pathophysiology. In conducting literature review on sepsis-related research, we employed systematic approach ensure comprehensiveness accuracy. Initially, conducted an extensive search through PubMed database, utilizing range keywords including "sepsis", "lactate", "lactylation", "epigenetic modification". aim was capture most recent research related pathophysiological mechanisms sepsis, metabolic disorders, lactylation. results revealed close link between sepsis dysfunction, particularly regulating responses inflammatory processes. Lactate, not only energy byproduct produced during glycolysis, affects activity various proteins, those involved regulation cell signaling, context changes levels may be closely associated severity prognosis disease. summary, lactylation, as emerging type epigenetic modification, provides new perspective for diagnosis treatment sepsis. Future needs further elucidate exact explore potential therapeutic target.

Language: Английский

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Insight into the roles of lactylation in macrophages: functions and clinical implications

Clinical Science, Journal Year: 2025, Volume and Issue: 139(02), P. 151 - 169

Published: Jan. 1, 2025

Lactylation, a post-translational modification, has been linked to gene transcription regulation through epigenetic modulation in various pathophysiological processes. The lactylation regulatory proteins, known as writers, erasers, and readers, govern their dynamics by adding, removing, recognizing lactyl groups on proteins. Macrophages, cells of the immune system, maintain homeostasis, responding dynamically diverse internal external stimuli. Emerging researches unveil that lactylation, inducing macrophage activation polarization, affects functionality pathological conditions such inflammation, tumor microenvironment, fibrosis. Evidence progressively indicates lactate-driven alterations levels within macrophages can influence pathogenesis numerous diseases. This review aims systematically summarize research progress macrophages, explore its functions mechanisms which contributes pathology different disease phenotypes, propose future directions along with potential diagnostic therapeutic strategies.

Language: Английский

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Metabolic Reprogramming and Its Regulatory Mechanism in Sepsis-Mediated Inflammation

Journal of Inflammation Research, Journal Year: 2023, Volume and Issue: Volume 16, P. 1195 - 1207

Published: March 1, 2023

Abstract: Sepsis is a systemic inflammatory disease caused by an infection that can lead to multiple organ failure. alters energy metabolism, leading metabolic reprogramming of immune cells, which consequently disrupts innate and adaptive responses, triggering hyperinflammation immunosuppression. This review summarizes its regulatory mechanism in sepsis-induced immunosuppression, highlights the significance intricacies cell reprogramming, emphasizes pivotal role mitochondria regulation treatment sepsis. provides up-to-date overview relevant literature inform future research directions understanding sepsis immunometabolism. Metabolic has great promise as new target for future. Keywords: cell, hyperinflammation, immunometabolism,

Language: Английский

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The relationship and clinical significance of lactylation modification in digestive system tumors

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: July 15, 2024

Lactylation, an emerging post-translational modification, plays a pivotal role in the initiation and progression of digestive system tumors. This study presents comprehensive review lactylation tumors, underscoring its critical involvement tumor development progression. By focusing on metabolic reprogramming, modulation microenvironment, molecular mechanisms regulating progression, potential targeting as therapeutic strategy is highlighted. The research reveals that participates gene expression regulation cell signaling by affecting states histones non-histone proteins, thereby influencing pathways immune evasion cells. Furthermore, this assesses feasibility target, providing insights for clinical treatment gastrointestinal cancers. Future should concentrate elucidating lactylation, developing efficient inhibitors, validating their efficacy trials, which could transform current cancer immunotherapy approaches. In summary, emphasizes crucial tumorigenesis through detailed analysis significance.

Language: Английский

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Malvidin promotes PGC-1α/Nrf2 signaling to attenuate the inflammatory response and restore mitochondrial activity in septic acute kidney injury

Chemico-Biological Interactions, Journal Year: 2023, Volume and Issue: 388, P. 110850 - 110850

Published: Dec. 20, 2023

Language: Английский

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Lactate and Lactylation: Clinical Applications of Routine Carbon Source and Novel Modification in Human Diseases

Molecular & Cellular Proteomics, Journal Year: 2023, Volume and Issue: 22(10), P. 100641 - 100641

Published: Sept. 6, 2023

Cell metabolism generates numerous intermediate metabolites that could serve as feedback and feed-forward regulation substances for posttranslational modification. Lactate, a metabolic product of glycolysis, has recently been conceptualized to play pleiotropic role in shaping cell identities through rewiring epigenetic modifications. Lactate-derived carbons, sourced from glucose, mediate the crosstalk among lactate, lactylation. Furthermore, multiple fates lactate make it an ideal substrate imaging clinical application. Several studies have identified crucial protein lactylation human diseases associated with fate determination, embryonic development, inflammation, neoplasm, neuropsychiatric disorders. Herein, this review will focus on lactate-derived carbon provide useful information further research therapeutic approaches diseases. We comprehensively discuss its reprogramming modification during translation prospects hyperpolarized signal, lactyl diseases, application other techniques omics.

Language: Английский

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Potential biomarker for diagnosis and therapy of sepsis: Lactylation

Immunity Inflammation and Disease, Journal Year: 2023, Volume and Issue: 11(10)

Published: Oct. 1, 2023

As a disease that has plagued human health for decades, sepsis so far had no specific diagnostic or therapeutic indicators. The discovery of lactylation modifications not only uncovered the deep-rooted causes changing between lactate level and pathophysiology immunology sepsis, but also reaffirmed inevitable link metabolic reprogramming epigenetic in sepsis. Lactylation modification became potential marker diagnosis guiding treatment

Language: Английский

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Methylsulfonylmethane (MSM) Supplementation in Adult Horses Supports Improved Skeletal Muscle Inflammatory Gene Expression Following Exercise

Animals, Journal Year: 2025, Volume and Issue: 15(2), P. 215 - 215

Published: Jan. 14, 2025

Methylsulfonylmethane (MSM) is a sulfur-containing molecule with reported anti-inflammatory and antioxidant activities. Exercise causes the formation of free radicals stimulates inflammatory gene expression in leukocytes skeletal muscle. The hypothesis that dietary supplementation MSM alters exercise-mediated oxidant response was assessed unfit adult thoroughbred geldings. Ten geldings (6.7 ± 1.6 yr) were assigned to diet supplemented without (CON, n = 5) or 21 g (n for 30 days. Following period, horses performed standardized exercise test (SET) blood collections before (t 0), 10 min, 1 h, 4 24 h post-SET. Skeletal muscle biopsies retrieved from middle gluteus post-SET total RNA isolation. All rested 120 days experiment repeated cross-over design. Plasma capacity unaffected (p > 0.05) by either MSM. glutathione peroxidase activity less < than CON. IL6, IL8, IL10, TNFα diet. Transcriptomic analysis revealed 35 genes differentially expressed (DEG; p 2-fold more exercise; no DEGs noted. A comparison contrasts contained greater number exercise-responsive (630; logFC 0.2; q CON (237), many these mapping immune (71) cytokine signal transduction (60) pathways. These results suggest as aid improved responses following exercise.

Language: Английский

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