ArticleCell death & disease2019
Adrenomedullin alleviates the pyroptosis of Leydig cells by promoting autophagy via the ROS-AMPK-mTOR axis.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers.
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123 citing papers in PubMed, 268 citations in OpenAlex.
- DNMT1 Regulates Testosterone Synthesis in Aged Rat Leydig Cells via FTO-Mediated HSP90AA1 mAging cell · 2026Article
- Rg1 activates the AMPK/mTOR-autophagy axis and inhibits the NOD-like receptor 3 inflammasome to alleviate pyroptosis in periodontal ligament fibroblasts.Odontology · 2026Article
- Endothelial cell-specific knockout of ATG5 ameliorates inflammation and renal fibrosis by regulating pyroptosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Targeting programmed cell death in male infertility: pathogenic mechanisms and therapeutic strategies.Molecular biology reports · 2026Review
- Natural astaxanthin enhances testosterone synthesis by improving mitochondrial function and reducing oxidative stress in Leydig cells.Poultry science · 2026Article
- REDD1 deficiency alleviates podocyte PANoptosis and restores autophagy in diabetic kidney disease.Molecular medicine (Cambridge, Mass.) · 2026Article
- METTL14 modulates the autophagy-pyroptosis pathway in fibroblasts by modifying BECN1 through mCell biology and toxicology · 2026Article
- Targeting AMPK Networks for Male Reproductive Health: Mechanisms and Emerging Therapies.Cells · 2026Review
- Curcumin modulates hepatic pyroptosis-autophagy crosstalk induced by aflatoxin B1 via rumen microbiota-blood-liver axis.Microbiome · 2026Article
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- Pyroptosis: mechanism and therapeutic strategies with intervertebral disc degeneration.Experimental & molecular medicine · 2026Review
- Hesperetin alleviates neuronal pyroptosis by promoting mitophagy via DHCR24/BACE1 signaling pathway after subarachnoid hemorrhage in mice.Apoptosis : an international journal on programmed cell death · 2026Article
- Cross-talk among novel programmed cell death pathways: a decisive network in renal ischemia-reperfusion injury.Frontiers in immunology · 2026Review
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Empagliflozin Inhibits Cadmium-Induced Hepatic Cell Apoptosis Through Endoplasmic Reticulum Stress and Autophagy Pathways.Biological trace element research · 2025Article
- Antcin-H, a natural triterpene derived fromJournal of traditional and complementary medicine · 2025Article
- The Role of Environmental Endocrine Disruptors on Leydig Cell Death and Senescen.The world journal of men's health · 2025Review
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- Vincamine induces cytoprotective autophagy via regulation of ampk/mtor signaling pathway in gentamicin-induced hepatotoxicity and nephrotoxicity in rats.Scientific reports · 2025Article
- Article
63 more citing papers are in PubMed but not listed here.
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12 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adrenomedullin (ADM) exerts anti-oxidant, anti-inflammatory and anti-apoptotic effects in Leydig cells. However, the role and mechanism of ADM in the pyroptosis of Leydig cells are poorly understood. This study first showed the protective effects of ADM on the pyroptosis and biological functions of Leydig cells exposed to lipopolysaccharide (LPS) by promoting autophagy. Primary rat Leydig cells were treated with various concentrations of LPS and ADM, together with or without N-acetyl-L-cysteine (NAC) or 3-methyladenine (3-MA). Cell proliferation was detected through CCK-8 and BrdU incorporation assays, and ROS level was measured with the DCFDA assay. Real-time PCR, western blot, immunofluorescence, transmission electron microscopy, TUNEL and flow cytometry were performed to examine ADM's effect on the pyroptosis, autophagy and steroidogenic enzymes of Leydig cells and AMPK/mTOR signalling. Like NAC, ADM dose-dependently reduced LPS-induced cytotoxicity and ROS overproduction. ADM also dose-dependently ameliorated LPS-induced pyroptosis by reversing the increased expression of NLRP3, ASC, caspase-1, IL-1β, IL-18, GSDMD, caspase-3, caspase-7, TUNEL-positive and PI and active caspase-1 double-stained positive rate, DNA fragmentation and LDH concentration, which could be rescued via co-incubation with 3-MA. ADM dose-dependently increased autophagy in LPS-induced Leydig cells, as confirmed by the increased expression of LC3-I/II, Beclin-1 and ATG-5; decreased expression of p62 and autophagosomes formation; and increased LC3-II/LC3-I ratio. However, co-treatment with 3-MA evidently decreased autophagy. Furthermore, ADM dose-dependently rescued the expression of steroidogenic enzymes, including StAR, P450scc, 3β-HSD and CYP17, and testosterone production in LPS-induced Leydig cells. Like rapamycin, ADM dose-dependently enhanced AMPK phosphorylation but reduced mTOR phosphorylation in LPS-induced Leydig cells, which could be rescued via co-incubation with 3-MA. In addition, pyroptosis was further decreased, and autophagy was further promoted in LPS-induced Leydig cells upon co-treatment with ADM and rapamycin. ADM may protect the steroidogenic functions of Leydig cells against pyroptosis by activating autophagy via the ROS-AMPK-mTOR axis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.