Neurology, Год журнала: 2025, Номер 104(11)
Опубликована: Май 12, 2025
Язык: Английский
Theranostics, Год журнала: 2025, Номер 15(5), С. 1787 - 1821
Опубликована: Янв. 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.
Язык: Английский
Процитировано
2
The FASEB Journal, Год журнала: 2025, Номер 39(2)
Опубликована: Янв. 20, 2025
Abstract Macrophage infiltration and activation is a key factor in the progression of diabetic nephropathy (DN). However, aerobic glycolysis induced by m6A methylation modification plays role M1‐type macrophages, but specific mechanism remains unclear DN. In this study, expression demethylase Fto bone marrow derived macrophages primary kidney from db/db mice. Loss gain‐of‐function analysis were performed to assess Transcriptome MeRIP‐seq association was identified target gene Npas2. we found that exhibits low type 2 DN Npas2 mediated regulates glucose metabolism reprogramming participate process Furthermore, reduces level through Prrc2a‐dependent mechanism, decreasing its stability. This mediates inflammation M1 regulating Hif‐1α signaling pathway. may act as suppressor m6A/Npas2/Hif‐1α axis. findings providing new basis for prevention treatment
Язык: Английский
Процитировано
1
Renal Failure, Год журнала: 2025, Номер 47(1)
Опубликована: Фев. 26, 2025
The kidney is essential for lactate metabolism. Under normal conditions, the renal cortex mainly absorbs and metabolizes lactate, with minimal amounts excreted in urine. This process part of a glucose-lactate recycling system between medulla. In conditions such as acute injury (AKI) diabetic disease (DKD), kidney's ability to metabolize impaired, leading accumulation exacerbated dysfunction. Novel post-translational modifications, lactylation, are critical pathophysiology by modulating gene transcription, protein function, cellular Lactylation involved inflammatory responses tumor promotion AKI, mitochondrial dysfunction DKD, progression clear cell carcinoma (ccRCC). lactate-lactylation axis central Warburg effect ccRCC, where cells preferentially rely on glycolysis rather than oxidative phosphorylation. Understanding mechanisms metabolism lactylation diseases may offer new therapeutic strategies. review examines role esters, especially diseases, focus their regulatory potential targets.
Язык: Английский
Процитировано
1
Journal of Ethnopharmacology, Год журнала: 2024, Номер 335, С. 118698 - 118698
Опубликована: Авг. 14, 2024
Язык: Английский
Процитировано
4
Kidney International Reports, Год журнала: 2024, Номер 9(12), С. 3386 - 3402
Опубликована: Окт. 4, 2024
Язык: Английский
Процитировано
4
Nature Reviews Nephrology, Год журнала: 2024, Номер unknown
Опубликована: Дек. 16, 2024
Язык: Английский
Процитировано
3
Journal of Diabetes Investigation, Год журнала: 2025, Номер unknown
Опубликована: Янв. 22, 2025
ABSTRACT Aim/Introduction Senescence is a key driver of age‐related kidney dysfunction, including diabetic disease. Oxidative stress activates cellular senescence, induces abnormal glycolysis, and associated with pyruvate kinase muscle isoform 2 (PKM2) dysfunction; however, the mechanisms linking PK activation to senescence have not been elucidated. We hypothesized that PKM2 by TEPP‐46 could suppress oxidative stress‐induced renal tubular cell injury senescence. Materials Methods To investigate effects on we conducted β‐galactosidase staining western blot analysis human primary cells (pRPTECs) treated hydrogen peroxide or without TEPP‐46. IL‐6 levels glycolytic flux were measured. Cell viability apoptosis assessed via MTS assay caspase 3 cleavage. For in vivo experiments, utilized CD‐1 db/db mice, fibrotic type diabetes model, which exhibit fibrosis. After 4 weeks intervention, fibrosis expression markers analyzed. Results In pRPTECs, increased number β‐galactosidase‐positive cells, (p16, p21, p53), p38 phosphorylation; co‐incubation suppressed these alterations. Hydrogen reduced viability, induced apoptosis, mesenchymal alterations, lactate production secretion; inhibitor mitigated effects. intervention fibrosis, tended reduce senescence‐associated molecules kidney. Conclusions be molecular target for protection against organ damage,
Язык: Английский
Процитировано
0
Cell Proliferation, Год журнала: 2025, Номер unknown
Опубликована: Апрель 10, 2025
ABSTRACT Lactate is not only a byproduct of glycolysis, but also considered an energy source, gluconeogenic precursor, signalling molecule and protein modifier during the process cellular metabolism. The discovery lactylation reveals multifaceted functions lactate in metabolism opens new avenues for lactate‐related research. Both have been implicated regulating numerous biological processes, including tumour progression, ischemic–hypoxic injury, neurodevelopment immune‐related inflammation. kidney plays crucial role metabolism, influencing levels while being regulated by lactate. Previous studies demonstrated importance pathogenesis acute injury (AKI) chronic disease (CKD). This review explores these diseases, comparing function metabolic mechanisms normal diseased kidneys from perspective lactylation. key regulatory roles different organs, multiple systems, various pathological states underlying AKI‐to‐CKD progression are summarised. Moreover, potential therapeutic targets future research directions across diseases identified.
Язык: Английский
Процитировано
0
Frontiers in Pharmacology, Год журнала: 2025, Номер 16
Опубликована: Апрель 25, 2025
Язык: Английский
Процитировано
0
Neurology, Год журнала: 2025, Номер 104(11)
Опубликована: Май 12, 2025
Язык: Английский
Процитировано
0