Ask about this productRelated genes to: Pde2a Blocking Peptide
- Gene:
- PDE2A NIH gene
- Name:
- phosphodiesterase 2A
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 11q13.4
- Locus Type:
- gene with protein product
- Date approved:
- 1997-11-10
- Date modifiied:
- 2016-10-05
Related products to: Pde2a Blocking Peptide
Related articles to: Pde2a Blocking Peptide
- Mitochondrial calcium signaling, particularly its glucagon-mediated oscillatory dynamics, plays a pivotal role in regulating hepatic metabolism and is known to be disrupted in steatotic liver disease. We recently identified the mitochondrial Na/Caexchanger NCLX as a key mediator of glucagon-induced mitochondrial calcium oscillations, essential for proper gluconeogenic function. Here, using hepatocyte-specific NCLX knockout (cKO) mice, we demonstrate that NCLX is critical for intrahepatic lipolysis and fatty acid oxidation (FAO); its loss impairs glucagon-stimulated lipid droplet catabolism and blunts FAO. Mechanistically, we find that NCLX deficiency disrupts allosteric activation of lipolytic enzymes and increases CPT1 sensitivity to malonyl-CoA-mediated inhibition, resulting in defective lipolysis and FAO. We further show that glucagon regulates hepatic NCLX via cAMP/PKA-dependent phosphorylation at NCLX Ser258. Notably, PDE2A acts as a negative regulator of this pathway by degrading mitochondrial cAMP. Hepatic mitochondrial PDE2A abundance and cAMP-degrading activity are elevated in HFD, and in vivo BAY 60-7550 treatment suppresses mitochondrial cAMP degradation and augments PKA signaling in steatosic livers. Pharmacologic inhibition of PDE2A with BAY 60-7550 enhances NCLX phosphorylation, restores mitochondrial calcium efflux and oscillations, and stimulates FAO in an NCLX-dependent manner. Importantly, we uncover that cAMP/PKA-dependent phosphorylation of NCLX at Ser258 is suppressed in human steatotic livers, and that pharmacologic inhibition of PDE2A ameliorates hepatic FAO and steatosis in both dietary and genetic MASLD models. Collectively, our findings establish the glucagon-PKA-PDE2A-NCLX signaling axis as a key metabolic rheostat integrating mitochondrial calcium dynamics with lipid homeostasis, providing a promising therapeutic target for MASLD. - Source: PubMed
Publication date: 2026/08/25
Assali Essam ATaha MahmoudSalhab AhmadAmer JohnnyKrishnan Karthickeyan ChellaKostic MarkoVeliova MichaelaBrownstein Alexandra JShirihai Orian SSafadi RifaatSekler Israel - Emerging evidence indicated that long non-coding RNAs (lncRNAs) play critical roles in mammalian reproductive physiology, yet their roles in asthenozoospermia (AS), a major contributor to male infertility, remain elusive. Here, we identify as a candidate lncRNA associated with impaired sperm function. expression was significantly elevated in semen from AS patients and negatively correlated with sperm concentration, total motility, and progressive motility. In mouse testes, was detected in spermatogonia, spermatocytes and spermatids with predominant cytoplasmic localization as well as in GC-2spd cells. Furthermore, overexpression reduced cell viability and migration and increased intracellular reactive oxygen species (ROS), whereas knockdown enhanced viability and migration and lowered ROS in GC-2spd cells. Bulk RNA-seq analysis revealed that the phosphodiesterase 2A (Pde2a), a key cGMP/cAMP-hydrolyzing enzyme, were upregulated when was knockdown. The GO enrichment and KEGG analysis of differentially expressed genes suggested the cyclic guanosine monophosphate (cGMP) process were enriched. Further validation found that suppressed . In clinical semen samples, and expression levels were inversely correlated, and both were closely associated with semen quality parameters. Collectively, these findings implicated and its downstream target as potential pathogenic regulators of sperm motility in AS. By linking lncRNA-mediated modulation of cGMP signaling and oxidative stress to spermatogenic cell function, our results demonstrated a plausible signaling axis underlying AS and suggests as promising candidates for biomarker development and therapeutic investigation in male infertility. - Source: PubMed
Publication date: 2026/08/07
Guo BingrouKe JunyiMai HanranZhang TingLu ZhaojinZheng ZilinLuo JieyiZhang YifanYan MeiYang ShuoQu YanxiaJiang FanLiu XiaopingChen HaoZuo Liandong - Adrenergic stimulation of brown adipocytes induces a robust detachment of mitochondria from lipid droplets (LD), which is followed by lipolysis and lipid catabolism. However, the signals inducing mitochondria attachment or detachment, and their role in lipid metabolism, remain unknown. Here, we reconstituted mitochondria-LD interaction in brown adipocyte tissue (BAT) ex vivo. We find that removal of mitochondria from lipid droplets permits higher lipolytic activity of recombinant lipases. Testing the effect of thermogenic secondary messengers and metabolites on attachment and detachment identified elevated mitochondrial matrix calcium as a potent inducer of detachment. Further, deletion of the mitochondrial sodium/calcium exchanger, NCLX, resulted in reduced attachment and increased detachment, while activation of NCLX increased attachment. We find that elevated matrix calcium causes detachment by inducing architectural transformation of peridroplet mitochondria (PDM) from their typical LD-surface-bound crescent shape into a round shape. PDE2A inhibition activates NCLX and increases PDM content in BAT in vitro and in vivo. We conclude that a surge in mitochondrial matrix calcium ions serves as a potent signal to induce mitochondrial detachment from lipid droplets, thereby facilitating lipolysis. - Source: PubMed
Publication date: 2026/07/03
Acin-Perez RebecaAssali Essam AVeliova MichaelaNgo JenniferBrownstein Alexandra JVillalobos FranciscoPetcherski AntonHernansanz-Agustin PabloKim-Vasquez DoyeonXu ShiliTamboline MikaylaSilva Raquel MariaUpcher AlexanderShu CynthiaFerriss Daniel ELiesa MarcEnriquez Jose AntonioSekler IsraelShirihai Orian S - Metabolic reprogramming is closely linked to tumor proliferation, invasion, and immune escape. Despite its central role in amino acid metabolism, the regulatory mechanisms of asparagine metabolism in hepatocellular carcinoma (HCC) progression remain poorly characterized. Rather than focusing on canonical metabolic genes, prognostic markers were identified from co-expression modules associated with asparagine metabolism signatures. Using the TCGA database and asparagine metabolism-related gene sets, a prognostic risk-scoring model was developed through differential expression analysis, univariate Cox regression, and the LASSO algorithm and externally validated with the GEO dataset (GSE14620). Survival analysis, ROC curve evaluation, nomogram construction, scRNA-seq, GSEA, and drug sensitivity analysis were performed to systematically delineate the molecular mechanisms by which asparagine metabolism drives HCC progression. A three-gene signature comprising BOP1, SAC3D1, and PDE2A effectively stratified patients into high- and low-risk groups. High-risk patients exhibited markedly poorer overall survival, enrichment in tumor proliferation-associated pathways, increased tumor purity, reduced immune cell infiltration, and a substantially higher TP53 mutation rate (38% vs. 13%). In contrast, the low-risk group showed enrichment in pathways linked to hepatoblastoma suppression and liver function, alongside improved predicted response to immunotherapy. Single-cell analysis identified NK cells and endothelial cells as central mediators of asparagine metabolism-driven HCC progression, with BOP1, SAC3D1, and PDE2A displaying dynamic expression patterns during differentiation. Furthermore, the high-risk group was predicted to be more sensitive to chemotherapeutics such as cyclophosphamide and 5-fluorouracil. These findings highlight a potential interplay between nitrogen metabolism and asparagine metabolism in HCC and suggest mechanisms by which these pathways may influence NK cell and endothelial cell function to promote disease progression. This study establishes a novel prognostic model and identifies potential chemotherapeutic vulnerabilities in high-risk patients, warranting further experimental and clinical validation. - Source: PubMed
Publication date: 2026/05/15
Feng JiantingWei KaihuaLi NanaLi YinshiDu FeiLv MengjiaoMa LifeiWang SuwenNiu ShuliangFeng Liang - Suicide is a complex public health challenge. Although psychosocial factors are important, molecular dysregulations in the prefrontal cortex (PFC) have been implicated in suicidal behavior. - Source: PubMed
Publication date: 2026/05/20
Ramos-Rosales Daniel FEcheverria-Carrillo Cristian ABarraza-Salas MarceloCervantes-Flores MaribelSalas-Pacheco Sergio MMéndez-Hernández Edna MCastellanos-Juárez Francisco XLlave-León Osmel LaSandoval-Carrillo Ada ASalas-Pacheco José M