Andrographolide regulates H3 histone lactylation by interfering with p300 to alleviate aortic valve calcification

Wang, Chunli; Wang, Shunshun; Wang, Zijun; Han, Juanjuan; Jiang, Nan; Qu, Linghang; Xu, Kang

doi:10.1111/bph.16332

Cited by 18 publications

(2 citation statements)

References 48 publications

(61 reference statements)

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“…Expression of pro-inflammatory genes induced by TNF-α was reversed by CA. The unique combination of matrix molecules, including ACAN and COL2A1 provides cartilage from damage due to load [21][22][23]. The integrity of ECM is the basis for protecting chondrocytes from stimuli.…”

Section: Discussionmentioning

confidence: 99%

Cholic acid mitigates osteoarthritis by inhibiting the NF-κB/PERK/SIRT1 signaling pathway

SHENG,

YI,

et al. 2024

BIOCELL

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Introduction: Cholic acid (CA) is a natural steroid useful in treating chronic bronchitis and cholecystitis. On the other hand, its potential impact on osteoarthritis (OA) is unknown. Objective: Using an in vitro and in vivo osteoarthritis model, we sought to assess the chondroprotective properties of CA. Methods: We employed the Cell Counting Kit-8 to measure the impact of CA on chondrocyte activity to assess the toxicity of the cells. Multiple molecular biology experimental techniques were used to investigate potential signaling pathways that CA may use to prevent inflammation and give chondrocytes protection. Furthermore, how CA affects the OA model in Sprague-Dawley (SD) rats was evaluated. Results: CA significantly suppressed the up-regulation of the interleukin-1 β (IL-1β), cyclooxygenase-2 (COX-2), and matrix metalloproteinase 13 (MMP-13) and the downregulation of aggrecan and type II collagen A1 (COL2A) in chondrocytes treated tumor necrosis factor-alpha (TNF-α). Differentially expressed genes (DEG) enrichment revealed IL-17, TNF, chemokine, cytokine-cytokine receptor, toll-like receptor, and nucleotide oligomerization domain-like receptor were the primary signaling pathways. The enriched DEGs included CXCL6, CCL20, MMP3, CXCL3, CXCL11, CCL5, CXCL10, MMP9, MMP13, and CXCL2; these DEGs are involved in inflammatory responses and their expression induced by TNF-α was reversed by CA treatment. CA inhibits p65 nuclear translocation and inhibitory subunit kappa B alpha (IκBα) phosphorylation induced by TNF-α. Furthermore, CA attenuated protein expression of protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositolrequiring transmembrane kinase/endoribonuclease 1α (IRE1α), glucose regulatory protein 78 (GRP78), and sirtuin 1 (SIRT1), and down-regulation of phosphorylation of AMP-activated protein kinase-α (p-AMPKα) in TNF-α-treated chondrocytes. Conclusions: CA significantly ameliorated cartilage degradation in the OA rat model. CA alleviated the inflammatory response through the nuclear factor kappa B/PERK/SIRT1 axis and ameliorated cartilage degradation.

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Section: Discussionmentioning

confidence: 99%

Cholic acid mitigates osteoarthritis by inhibiting the NF-κB/PERK/SIRT1 signaling pathway

SHENG,

YI,

et al. 2024

BIOCELL

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“…Andrographolide (AGP) effectively reduced calcium deposition in valve interstitial cells (VICs) and improved aortic valve calcification. Wang and colleagues showed that AGP reduces calcification by disrupting H3Kla through p300 [161]. Research has demonstrated that lactylation modification plays a role in the development of atherosclerosis, making it a significant focus in atherosclerosis research, as shown in Figure 2C.…”

Section: Atherosclerosis and Lactylationmentioning

confidence: 99%

Lactylation Modification in Cardiometabolic Disorders: Function and Mechanism

Li,

Cai,

Tang

et al. 2024

Metabolites

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Cardiovascular disease (CVD) is recognized as the primary cause of mortality and morbidity on a global scale, and developing a clear treatment is an important tool for improving it. Cardiometabolic disorder (CMD) is a syndrome resulting from the combination of cardiovascular, endocrine, pro-thrombotic, and inflammatory health hazards. Due to their complex pathological mechanisms, there is a lack of effective diagnostic and treatment methods for cardiac metabolic disorders. Lactylation is a type of post-translational modification (PTM) that plays a regulatory role in various cellular physiological processes by inducing changes in the spatial conformation of proteins. Numerous studies have reported that lactylation modification plays a crucial role in post-translational modifications and is closely related to cardiac metabolic diseases. This article discusses the molecular biology of lactylation modifications and outlines the roles and mechanisms of lactylation modifications in cardiometabolic disorders, offering valuable insights for the diagnosis and treatment of such conditions.

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Lactylome Analysis Unveils Lactylation‐Dependent Mechanisms of Stemness Remodeling in the Liver Cancer Stem Cells

Feng,

Wu,

Chi

et al. 2024

Advanced Science

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Lactate plays a critical role as an energy substrate, metabolite, and signaling molecule in hepatocellular carcinoma (HCC). Intracellular lactate‐derived protein lysine lactylation (Kla) is identified as a contributor to the progression of HCC. Liver cancer stem cells (LCSCs) are believed to be the root cause of phenotypic and functional heterogeneity in HCC. However, the impact of Kla on the biological processes of LCSCs remains poorly understood. Here enhanced glycolytic metabolism, lactate accumulation, and elevated levels of lactylation are observed in LCSCs compared to HCC cells. H3K56la was found to be closely associated with tumourigenesis and stemness of LCSCs. Notably, a comprehensive examination of the lactylome and proteome of LCSCs and HCC cells identified the ALDOA K230/322 lactylation, which plays a critical role in promoting the stemness of LCSCs. Furthermore, this study demonstrated the tight binding between aldolase A (ALDOA) and dead box deconjugate enzyme 17 (DDX17), which is attenuated by ALDOA lactylation, ultimately enhancing the regulatory function of DDX17 in maintaining the stemness of LCSCs. This investigation highlights the significance of Kla in modulating the stemness of LCSCs and its impact on the progression of HCC. Targeting lactylation in LCSCs may offer a promising therapeutic approach for treating HCC.

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Andrographolide regulates H3 histone lactylation by interfering with p300 to alleviate aortic valve calcification

Cited by 18 publications

References 48 publications

Cholic acid mitigates osteoarthritis by inhibiting the NF-κB/PERK/SIRT1 signaling pathway

Cholic acid mitigates osteoarthritis by inhibiting the NF-κB/PERK/SIRT1 signaling pathway

Lactylation Modification in Cardiometabolic Disorders: Function and Mechanism

Lactylome Analysis Unveils Lactylation‐Dependent Mechanisms of Stemness Remodeling in the Liver Cancer Stem Cells

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