PTB domain and leucine zipper motif 1 (APPL1) inhibits myocardial ischemia/hypoxia-reperfusion injury via inactivation of apoptotic protease activating factor-1 (APAF-1)/Caspase9 signaling pathway

Bai, Lina; Yang, Junhua; Zhang, Hong; Liao, Wei; Cen, Yunguang

doi:10.1080/21655979.2021.1954841

Cited by 5 publications

(3 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Caspase-9 plays a crucial role in initiating apoptosis during the apoptotic process. Stimulation of apoptotic signaling activates the Caspase-9 precursor, which then triggers the Caspase-3 activation and initiates the Caspase cascade reaction, ultimately leading to apoptosis [36]. We further confirmed the anti-apoptotic effect of HCT-f by measuring the content and relative mRNA expression of Caspase-3 and Caspase-9, two proteins closely associated with apoptosis.…”

Section: Effects Of Hct-f On Apoptotic Cell Deathsupporting

confidence: 66%

Inhibition of LPS-Induced Skin Inflammatory Response and Barrier Damage via MAPK/NF-κB Signaling Pathway by Houttuynia cordata Thunb Fermentation Broth

Song,

Fang,

Wang

et al. 2024

Foods

View full text Add to dashboard Cite

Houttuynia cordata Thunb is rich in active substances and has excellent antioxidant and anti-inflammatory activity. Scanning electron microscopy and gel permeation chromatography were used to analyze the molecular characteristics of the fermentation broth of Houttuynia cordata Thunb obtained through fermentation with Clavispora lusitaniae (HCT-f). The molecular weight of HCT-f was 2.64265 × 105 Da, and the polydispersity coefficient was 183.10, which were higher than that of unfermented broth of Houttuynia cordata Thunb (HCT). By investigating the active substance content and in vitro antioxidant activity of HCT-f and HCT, the results indicated that HCT-f had a higher active substance content and exhibited a superior scavenging effect on 2,2-diphenyl-1-picrylhydrazyl radicals and hydroxyl radicals, with IC50 values of 11.85% and 9.01%, respectively. Our results showed that HCT-f could effectively alleviate the increase in the secretion of inflammatory factors and apoptotic factors caused by lipopolysaccharide (LPS) stimulation, and had a certain effect on repairing skin barrier damage. HCT-f could exert an anti-inflammatory effect by down-regulating signaling in the MAPK/NF-κB pathway. The results of erythrocyte hemolysis and chicken embryo experiments showed that HCT-f had a high safety profile. Therefore, this study provides a theoretical basis for the application of HCT-f as an effective ingredient in food and cosmetics.

show abstract

Section: Effects Of Hct-f On Apoptotic Cell Deathsupporting

confidence: 66%

Inhibition of LPS-Induced Skin Inflammatory Response and Barrier Damage via MAPK/NF-κB Signaling Pathway by Houttuynia cordata Thunb Fermentation Broth

Song,

Fang,

Wang

et al. 2024

Foods

View full text Add to dashboard Cite

show abstract

“…APPL1 is known to protect against cardiomyocyte senescence, cardiac fibrosis, and diabetic cardiomyopathy [ 61 – 63 ]. More importantly, APPL1 can function as a potential therapeutic target for myocardial I/R injury by antagonizing apoptosis, oxidative stress, cytotoxicity, and release of inflammatory cytokines [ 31 , 32 , 64 ]. In the same light, our experimentation uncovered that the downregulation of APPL1 mRNA was found in H/R-induced cardiomyocytes and miR-146a-5p mimics potently repressed APPL1 transcription.…”

Section: Discussionmentioning

confidence: 99%

METTL14-mediated N6-methyladenosine modification induces the ferroptosis of hypoxia/reoxygenation-induced cardiomyocytes

Zhao,

2024

J Cardiothorac Surg

View full text Add to dashboard Cite

Background Hypoxia/reoxygenation (H/R) induces cardiomyocyte ferroptosis, a core remodeling event in myocardial ischemia/reperfusion injury. Methyltransferase-like 14 (METTL14) emerges as a writer of N6-methyladenosine (m6A) modification. This study was conducted to decipher the role of METTL14 in H/R-induced cardiomyocyte ferroptosis. Methods Mouse cardiomyocytes HL-1 were cultured and underwent H/R treatment. The degree of ferroptosis after H/R treatment was appraised by the cell counting kit-8 assay, assay kits (ROS/GSH/Fe2+), and Western blotting (GPX4/ACSL4). The intracellular expressions of METTL14, pri-miR-146a-5p, miR-146a-5p, or adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) were examined by real-time quantitative polymerase chain reaction or Western blotting, with m6A quantification analysis and RNA immunoprecipitation to determine the total m6A level and the expression of pri-miR-146a-5p bound to DiGeorge critical region 8 (DGCR8) and m6A-modified pri-miR-146a-5p. The binding of miR-146a-5p to APPL1 was testified by the dual-luciferase assay. Results H/R treatment induced cardiomyocyte ferroptosis (increased ROS, Fe2+, and ACSL4 and decreased GSH and GPX4) and upregulated METTL14 expression. METTL14 knockdown attenuated H/R-induced cardiomyocyte ferroptosis. METTL14 induced the recognition of pri-miR-146a-5p by DGCR8 by increasing m6A modification on pri-miR-146a-5p, which promoted the conversion of pri-miR-146a-5p into miR-146a-5p and further repressed APPL1 transcription. miR-146a-5p upregulation or APPL1 downregulation limited the inhibitory effect of METTL14 downregulation on H/R-induced cardiomyocyte ferroptosis. Conclusion METTL14 promoted miR-146a-5p expression through the recognition and processing of pri-miR-146a-5p by DGCR8, which repressed APPL1 transcription and triggered H/R-induced cardiomyocyte ferroptosis.

show abstract

“…Bcl-2 protein can regulate the permeability of the mitochondrial membrane together with bax protein and release the Cyto-c in the mitochondria into the cytoplasm [21]. Cyto-c can bind to Apaf-1 protein, and the combination will promote the express of Caspase-9 protein to activate Caspase protein for apoptosis [22]. Diablo protein can bind to the interlocking family of apoptosis-inhibiting proteins [23].…”

Section: Introductionmentioning

confidence: 99%

A Cold-Inducible RNA Binding Protein Gene from Acanthopagrus schlegelii: Molecular Characterization, Expression, and Association with Apoptosis to Low-Temperature Stress

Mingliang,

Mingjun,

Yue

et al. 2023

Aquaculture Research

View full text Add to dashboard Cite

In this study, the complete cDNA sequence (1552 bp) of the cold-inducible RNA binding protein gene (cirbp gene) was successfully cloned from the liver in Acanthopagrus schlegelii (initial weight: 15.0 ± 2.3 g). Results showed that Ascirbp (cirbp gene from A. schlegelii) gene has 24 phosphorylation sites, no signal peptide, and no transmembrane helix structure. AsCIRBP, with a molecular weight of 18.84 ku and an isoelectric point of 9.04 was a stable protein that encodes 182 amino acids. Subcellular localization analysis of this protein showed that it was located in the nucleus. Sequence alignment results showed that the AsCIRBP amino acid sequences of various fishes including black porgy were highly conserved, especially the RNA recognition motif (RRM). Those results of real-time quantitative PCR (qRT-PCR) demonstrated that Ascirbp gene was specifically expressed in the liver tissue of black porgy and its expression was significantly increased under cold stress or cold acclimation. The RNA interference experiment results showed that Ascirbp-dsRNA could suppress the expression of Ascirbp gene in the liver of black porgy through intraperitoneal injection. After silencing the expression of Ascirbp gene, RNAi groups were more severely damaged in the structure of the liver tissue and more prone to apoptosis under cold stress than control groups. The results of the study on the linkage between Ascirbp gene expression and mitochondrial apoptosis pathways showed that changes in the expression of the Ascirbp gene had a significant effect on the expression of key genes of apoptosis. The most striking result from silencing the expression of the Ascirbp gene was that expressions of the bcl-2 and apaf-1 gene in the liver of black porgy decreased significantly, which can block the normal apoptotic process. After the disruption of the normal apoptotic process, the expressions of p53, bax, cyto-c, caspase-9, caspase-3, diablo, and caspase-1 gene were significantly affected. These results suggest that Ascirbp gene can inhibit apoptosis and protect tissue structure in the liver tissue of black porgy at low temperatures.

show abstract

PTB domain and leucine zipper motif 1 (APPL1) inhibits myocardial ischemia/hypoxia-reperfusion injury via inactivation of apoptotic protease activating factor-1 (APAF-1)/Caspase9 signaling pathway

Abstract: Cen (2021) PTB domain and leucine zipper motif 1 (APPL1) inhibits myocardial ischemia/hypoxia-reperfusion injury via inactivation of apoptotic protease activating factor-1 (APAF-1)/Caspase9 signaling pathway,

Cited by 5 publications

References 34 publications

Inhibition of LPS-Induced Skin Inflammatory Response and Barrier Damage via MAPK/NF-κB Signaling Pathway by Houttuynia cordata Thunb Fermentation Broth

Inhibition of LPS-Induced Skin Inflammatory Response and Barrier Damage via MAPK/NF-κB Signaling Pathway by Houttuynia cordata Thunb Fermentation Broth

METTL14-mediated N6-methyladenosine modification induces the ferroptosis of hypoxia/reoxygenation-induced cardiomyocytes

A Cold-Inducible RNA Binding Protein Gene from Acanthopagrus schlegelii: Molecular Characterization, Expression, and Association with Apoptosis to Low-Temperature Stress

Contact Info

Product

Resources

About