LDHA exacerbates myocardial ischemia-reperfusion injury through inducing NLRP3 lactylation DOI Creative Commons
Fang Li,

Zhenfei Yu,

Xiaoling Qian

et al.

BMC Cardiovascular Disorders, Journal Year: 2024, Volume and Issue: 24(1)

Published: Nov. 16, 2024

Myocardial ischemia-reperfusion (I/R) injury caused by revascularization treatment is the leading cause of cardiac damage aggravation in ischemic heart disease. Increasing evidence has unraveled crucial role pyroptosis myocardial I/R injury. Of note, lactylation been validated to be participated modulating pyroptosis. Hence, this study was aimed elaborate potential and mechanism damage. We established cell model through inducing hypoxia/reoxygenation (H/R) H9c2 cells. It uncovered that H/R stimulation drove cardiomyocyte upregulated total level. Further, we demonstrated promoting contributed H/R-evoked pyroptosis, whereas silencing LDHA led opposite results. More than that, confirmed facilitate NLRP3 at K245 site increase its protein stability. Our findings indicated activation abolished function deficiency H/R-treated In concert with aforementioned outcomes, knockout attenuated infarct size mice upregulation counteracted effects on I/R-evoked vivo. To summarize, current research provided persuasive promoted via enhancing induce

Language: Английский

Post-translational protein lactylation modification in health and diseases: a double-edged sword DOI Creative Commons
Hang Gong, Zhong Huang, Long Cheng

et al.

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

19
Astrocyte-derived lactate aggravates brain injury of ischemic stroke in mice by promoting the formation of protein lactylation DOI Creative Commons
Xiao‐Yi Xiong,

Xinru Pan,

Xia-Xia Luo

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(11), P. 4297 - 4317

Published: Jan. 1, 2024

Aim:Although lactate supplementation at the reperfusion stage of ischemic stroke has been shown to offer neuroprotection, whether role accumulated ischemia phase is neuroprotection or not remains largely unknown.Thus, in this study, we aimed investigate roles and mechanisms brain regulating injury stroke.Methods Results: Pharmacological inhibition production by either inhibiting LDHA glycolysis markedly attenuated mouse stroke.In contrast, additional supplement further aggravates injury, which may be closely related induction neuronal death A1 astrocytes.The contributing increased promotive formation protein lysine lactylation (Kla), while post-treatment did influence Kla levels with neuroprotection.Increased were found mainly neurons HPLC-MS/MS analysis immunofluorescent staining.Then, pharmacological blocking shuttle showed decreased brains.Additionally, Ldha specific knockout astrocytes (Aldh1l1 CreERT2 ; fl/fl mice, cKO) mice MCAO constructed results that level was accompanied a decrease volume cerebral infarction cKO compared control groups.Furthermore, writer p300 its antagonist A-485 significantly alleviates glial activation reduction level, resulting extending window improving functional recovery for stroke.Conclusion: Collectively, derived from promoting formation, suggesting presents new therapeutic targets treatment stroke.

Language: Английский

Citations

14
Comprehensive review of histone lactylation: Structure, function, and therapeutic targets DOI

Kaiwen Xu,

Zhang Keyi,

Yanshuang Wang

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 225, P. 116331 - 116331

Published: May 29, 2024

Language: Английский

Citations

13
Glycolysis: an emerging regulator of osteoarthritis DOI Creative Commons

Dingming Jiang,

Jianan Guo,

Yingquan Liu

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 9, 2024

Osteoarthritis (OA) has been a leading cause of disability in the elderly and there remains lack effective therapeutic approaches as mechanisms pathogenesis progression have yet to be elucidated. As OA progresses, cellular metabolic profiles energy production are altered, emerging reprogramming highlights importance specific pathways disease progression. crucial part glucose metabolism, glycolysis bridges inflammatory dysfunctions. Moreover, glycolytic pathway is involved different areas metabolism inflammation, associated with variety transcription factors. To date, it not fully elucidated whether changes its key enzymes onset or OA. This review summarizes important role mediating inducing tissue inflammation injury, aim providing further insights into pathological functions proposing new targets for treatment

Language: Английский

Citations

11
Unlocking the multifaceted molecular functions and diverse disease implications of lactylation DOI
Fengyang Jing, Jianyun Zhang, Heyu Zhang

et al.

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

Citations

8
H3K18 lactylation accelerates liver fibrosis progression through facilitating SOX9 transcription DOI

Shujun Wu,

Jianhong Li,

Yanfei Zhan

et al.

Experimental Cell Research, Journal Year: 2024, Volume and Issue: 440(2), P. 114135 - 114135

Published: June 18, 2024

Language: Английский

Citations

6
Therapeutic potential of microglial SMEK1 in regulating H3K9 lactylation in cerebral ischemia-reperfusion DOI Creative Commons

Wei-Yue Si,

Chunlin Yang,

Shu-Li Wei

et al.

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Dec. 26, 2024

Acute ischemic stroke (AIS) triggers immune responses and neuroinflammation, contributing to brain injury. Histone lactylation, a metabolic stress-related histone modification, plays critical role in various diseases, but its involvement cerebral ischemia remains unclear. This study utilized transient middle artery occlusion/reperfusion (MCAO/R) model an oxygen–glucose deprivation/reoxygenation (OGD/R) investigate the of microglial lactylation ischemia–reperfusion Lactate overload post-AIS increased while reduced SMEK1 expression microglia correlated with elevated lactate neuroinflammation. Microglia-specific deficiency enhanced production by inhibiting pyruvate dehydrogenase kinase 3-pyruvate (PDK3-PDH) pathway, increasing H3 lysine 9 (H3K9la), activating Ldha Hif-1α transcription, promoting glycolysis. overexpression improved neurological recovery mice. highlights as novel regulator potential therapeutic target for mitigating neuroinflammation enhancing after AIS. identifies

Language: Английский

Citations

5
Sucrose induces BoVDAC2 expression to preserve mitochondrial function and mitigate programmed cell death in broccoli DOI
Min Luo, Jiahui Chen, Shifeng Cao

et al.

Postharvest Biology and Technology, Journal Year: 2025, Volume and Issue: 222, P. 113382 - 113382

Published: Jan. 5, 2025

Language: Английский

Citations

0
H3K18 lactylation-mediated nucleotide-binding oligomerization domain-2 (NOD2) expression promotes bilirubin-induced pyroptosis of astrocytes DOI Creative Commons
Jing Li, Siyu Li, Qian Sun

et al.

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: March 12, 2025

Histone lactylation, a newly glycosis-related histone modification, plays crucial role in the regulation of gene expression various immune cells. However, lactylation astrocytes remains unclear. Here, this study showed that H3K18 (H3K18la) levels were upregulated primary under unconjugated bilirubin (UCB) stimulation and hippocampus encephalopathy (BE) rats. Inhibition glycolysis decreased H3K18la attenuated pyroptosis both vitro vivo. CUT& Tag RNA-seq results revealed was enriched at promoter nucleotide-binding oligomerization domain 2 (NOD2) promoted its transcription. Moreover, NOD2 boosted activation downstream mitogen-activated protein kinase (MAPK) nuclear factor-kappa B (NF-κB) signaling pathways, which exacerbated neuroinflammation BE. Collectively, provides novel understanding epigenetic astrocytes, interruption H3K18la/NOD2 axis may represent therapeutic strategy for treating encephalopathy.

Language: Английский

Citations

0
Lactylation of nuclear receptor coactivator 4 promotes ferritinophagy and glycolysis of neuronal cells after cerebral ischemic injury DOI

Xiaoyin He,

Zhenzhen Wang,

Qingbo Ge

et al.

Neuroreport, Journal Year: 2024, Volume and Issue: 35(14), P. 895 - 903

Published: July 24, 2024

Ischemic stroke remains a major cause of disability and mortality. Nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy is involved in cerebral ischemic injury. Additionally, lactylation regulates the progression ischemia This study aimed to investigate impact NCOA4 on glycolysis hippocampal neuron cells its modification. Middle artery occlusion (MCAO) mouse oxygen-glucose deprivation (OGD)-treated HT22 cell models were generated. Ferritinophagy was evaluated via detecting ferrous iron (Fe 2+ ), glutathione, malondialdehyde, protein levels. Glycolysis assessed by examining glucose consumption, lactate production, extracellular acidification rate. The using immunoprecipitation immunoblotting. Brain injury vivo analyzed measuring brain infarct neurological function. results showed that expression increased blood patients with acute stroke, peri-infarct region MCAO mice (increased percentage: 142.11%) OGD-treated 114.70%). Knockdown inhibited induced OGD. Moreover, OGD promoted at lysine (K)450 sites, which enhanced stability. interfering attenuated infarction dysfunction mice. Lactylation K450 sites promotes cells, thereby accelerating These findings suggest novel pathogenesis stroke.

Language: Английский

Citations

4