ArticleMolecular endocrinology (Baltimore, Md.)2012
Acid ceramidase (ASAH1) is a global regulator of steroidogenic capacity and adrenocortical gene expression.
Article in Molecular endocrinology (Baltimore, Md.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 37 citations in OpenAlex.
- Metabolic targeting of ASAH1 in combination with carnosine as a therapeutic strategy for TNBC.Molecular metabolism · 2026Article
- IGF2R: a new player in the IGF2 loop sustaining adrenocortical carcinogenesis.Cell communication and signaling : CCS · 2026Article
- xNNPCD identifies regulators of programmed cell death by integrating perturbation transcriptomes with cancer dependency profiles.bioRxiv : the preprint server for biology · 2026Article
- Constraint-based modelling of metabolic dysregulation in Gaucher disease: mitochondrial dysfunction and disrupted cholesterol homeostasis.Orphanet journal of rare diseases · 2026Article
- Potential endogenous lipid ligands for the nuclear receptor transcription factor Steroidogenic Factor-1.Advances in biological regulation · 2026Review
- The association between brominated flame retardants and serum testosterone levels in American adult men: NHANES 2013-2016.Frontiers in public health · 2025Article
- ASAH1 facilitates TNBC by DUSP5 suppression-driven activation of MAP kinase pathway and represents a therapeutic vulnerability.Cell death & disease · 2024Article
- Lipid metabolism-related genes are involved in the occurrence of asthma and regulate the immune microenvironment.BMC genomics · 2024Article
- Hepatotoxicity assessment of innovative nutritional supplements based on olive-oil formulations enriched with natural antioxidants.Frontiers in nutrition · 2024Article
- Genetic background in the rat affects endocrine and metabolic outcomes of bisphenol F exposure.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Article
- Characterization of 2,2',4,4'-tetrabromodiphenyl ether (BDE47)-induced testicular toxicity via single-cell RNA-sequencing.Precision clinical medicine · 2022Article
- Screening of sphingolipid metabolism-related genes associated with immune cells in myocardial infarction: a bioinformatics analysis.Journal of thoracic disease · 2022Article
- The role of lipid second messengers in aldosterone synthesis and secretion.Journal of lipid research · 2022Review
- Acid ceramidase improves mitochondrial function and oxidative stress in Niemann-Pick type C disease by repressing STARD1 expression and mitochondrial cholesterol accumulation.Redox biology · 2021Article
- Article
- Verteporfin treatment controls morphology, phenotype, and global gene expression for cells of the human nucleus pulposus.JOR spine · 2020Article
- Inhibition of acid ceramidase regulates MHC class II antigen presentation and suppression of autoimmune arthritis.Cytokine · 2020Article
- Article
- Acid Ceramidase Depletion Impairs Neuronal Survival and Induces Morphological Defects in Neurites Associated with Altered Gene Transcription and Sphingolipid Content.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
In H295R human adrenocortical cells, ACTH rapidly activates ceramide (Cer) and sphingosine (SPH) turnover with a concomitant increase in SPH-1-phosphate secretion. These bioactive lipids modulate adrenocortical steroidogenesis, primarily by acting as second messengers in the protein kinase A/cAMP-dependent pathway. Acid ceramidase (ASAH1) directly regulates the intracellular balance of Cer, SPH, and SPH-1-phosphate by catalyzing the hydrolysis of Cer into SPH. ACTH/cAMP signaling stimulates ASAH1 transcription and activity, supporting a role for this enzyme in glucocorticoid production. Here, the role of ASAH1 in regulating steroidogenic capacity was examined using a tetracycline-inducible ASAH1 short hairpin RNA H295R human adrenocortical stable cell line. We show that ASAH1 suppression increases the transcription of multiple steroidogenic genes, including Cytochrome P450 monooxygenase (CYP)17A1, CYP11B1/2, CYP21A2, steroidogenic acute regulatory protein, hormone-sensitive lipase, 18-kDa translocator protein, and the melanocortin-2 receptor. Induced gene expression positively correlated with enhanced histone H3 acetylation at target promoters. Repression of ASAH1 expression also induced the expression of members of the nuclear receptor nuclear receptor subfamily 4 (NR4A) family while concomitantly suppressing the expression of dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1. ASAH1 knockdown altered the expression of genes involved in sphingolipid metabolism and changed the cellular amounts of distinct sphingolipid species. Finally, ASAH1 silencing increased basal and cAMP-dependent cortisol and dehydroepiandrosterone secretion, establishing ASAH1 as a pivotal regulator of steroidogenic capacity in the human adrenal cortex.
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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.