Ask about this productRelated genes to: PRKACA antibody
- Gene:
- PRKACA NIH gene
- Name:
- protein kinase cAMP-activated catalytic subunit alpha
- Previous symbol:
- -
- Synonyms:
- PKACa
- Chromosome:
- 19p13.1
- Locus Type:
- gene with protein product
- Date approved:
- 2001-06-22
- Date modifiied:
- 2016-01-27
Related products to: PRKACA antibody
Related articles to: PRKACA antibody
- Pathogenic missense variants in PRKACA cause craniofacial, skeletal, and cardiac defects similar to Ellis-van Creveld syndrome. We report an individual with a previously unreported, de novo 3 amino acid deletion in PRKACA, identified on trio genome sequencing, and phenotypic features including severe neonatal hypotonia, appendicular skeletal abnormalities, osteopenia, aortic dilation, coronary dilation and vascular tortuosity. To assess this variant's effects, we performed in vitro and in vivo studies, generated an in-silico model, and assessed cell ciliation in induced pluripotent stem cells from the patient. Although the protein product of the PRKACA (PKA-Cα) 3 amino acid deletion variant is catalytically active, it shows reduced interaction with the regulatory subunits of PKA (particularly type II), resulting in overactivation of the PKA pathway and/or an inability to initiate hedgehog signaling. The deletion affects a key portion of PKA-C important for substrate tethering. Patient-derived iPSC have reduced ciliation compared to controls. Collectively, this supports that the PRKACA variant is pathogenic, and we propose that it is causal for our patient's unique skeletal dysplasia and vasculopathy phenotypes. This expands the phenotypic spectrum of pathogenic variants in PRKACA and suggests that affected individuals may require periodic screening for aortic and coronary dilation as well as osteopenia. - Source: PubMed
Publication date: 2026/05/18
Weaver K NicoleBroeckel Jan WBrown KariWasserman HalleyWu JianNeal AshleyPrada Carlos EKleinschmidt Neil LennartMachal Erik M FBertinetti DanielaRuiz-Perez Victor LTaylor SusanBrugmann SamanthaHerberg Friedrich - Cylindrospermopsin (CDN) is a highly toxic secondary metabolite of cyanobacteria that is reported to induce severe organ toxicity. The current investigation was conducted to explore cardiotoxic potential of CDN in a dose-dependent manner. Thirty-two Sprague Dawley rats were apportioned into control, CDN low dose (0.105 μg/kg) group, CDN (0.140 μg/kg) moderate dose group, and CDN high dose (0.175 μg/kg) treated group through oral route. CDN administration induced severe disruption of sympathetic β-adrenergic pathway via suppressing the expression of cAMP responsive element-binding protein 1 (CREB1), guanine nucleotide-binding protein (GNAS), Protein Kinase CAMP-Activated Catalytic Subunit Alpha (PRKACA), β1-adrenoceptor (ADRB1)/β2-adrenoceptor (ADRB2) while upregulating the expression of phospholamban (PLN) at all the tested doses. Besides, CDN intoxication reduced HR while escalating IVSd, IVSs, PWd, PWs, LVIDd, ESV, EDV and LVIDs in a dose-response manner. The catalytic activities of HO-1, GPx, SOD, GSR, CAT, and GST were suppressed while the levels of MDA and ROS were augmented following the exposure to CDN. Additionally, CDN administration upregulated the levels of CK-MB, LDH, CRP, CPK, Troponin (I and T), and BNP. Cardiac tissues exhibited elevated levels of COX-2, NF-κB, IL-6, IL-1β, and TNF-α in a dose-dependent manner. Moreover, CDN exposure induced severe myocardial disruptions including vascular congestion, myofibrillar degeneration, cytoplasmic vacuolization, extensive fibers disarray, and a high rate of inflammatory cells infiltration. These findings highlight the cardiotoxic potential of CDN at all the tested doses thereby warranting further clinical investigation to elucidate these impacts in humans. - Source: PubMed
Publication date: 2026/05/15
Al-Aream Maha AAlsharif Khalaf FAlzahrani Fuad MAlzahrani Khalid JAzmat Muhammad BilalEissa MohamedHassan Hesham M - Endometriosis is a prevalent gynecological disorder characterized by chronic inflammation. Pyroptosis, a type of programmed proinflammatory cell death, plays a crucial role in various inflammatory diseases. However, its specific mechanism in endometriosis remains unclear. This study integrated transcriptome data of patients with endometriosis from the GEO database with a pyroptosis-related gene set to identify core pyroptosis markers associated with endometriosis. Bioinformatics methods were employed to analyze the expression profiles and diagnostic values of these genes. The expression of these genes was validated in clinical specimens using qRT-PCR. The specific role of NLRP1 in endometriosis was subsequently explored using CCK-8, wound healing, Transwell, qRT-PCR and Western blot assays on cell lines. We identified eight pyroptosis markers closely related to endometriosis, among which the expression of NLRP1, PRKACA, and IL-6 were significantly upregulated in patients with endometriosis. The expression patterns of these genes were also confirmed in clinical specimens and cell lines. The results of functional experiments indicated that NLRP1 knockdown inhibited the proliferation, migration, and invasion of 12Z cells. Mechanistic studies revealed that downregulating NLRP1 expression reduced the expression of key molecules in the NF-κB signaling pathway and downstream caspase-1, GSDMD-N. This suggests that NLRP1 promotes pyroptosis by activating the NF-κB signaling pathway, thereby driving the progression of endometriosis. This study reveals a novel mechanism through which NLRP1 activates pyroptosis through the NF-κB signaling pathway and promotes the progression of endometriosis. NLRP1 may serve as a potential diagnostic biomarker and therapeutic target for endometriosis. - Source: PubMed
Publication date: 2026/05/14
Cong ShanshanZhang BingDai ShuqinFu YaoMaowulieti GulijianatiJiang LipingYuan HuaZhao Shaojie - Fibrolamellar hepatocellular carcinoma (FLC) is a rare and distinct histologic subtype of hepatocellular carcinoma that typically arises in non-cirrhotic livers of adolescents and young adults without underlying viral hepatitis or chronic liver disease. Accounting for less than 1% of all primary liver cancers, FLC is characterized by unique clinical, radiologic, and molecular features, most notably the highly characteristic fusion. Due to its rarity and frequently nonspecific presentation, diagnosis is often delayed or misinterpreted as by benign hepatic lesions such as focal nodular hyperplasia or adenoma. This report presents a rare case of metastatic FLC in a young adult who initially presented with right upper quadrant pain, anemia, and preserved hepatic function. Imaging revealed a large hepatic mass with a central non-enhancing area suggestive of necrosis, and histopathologic evaluation aided in the diagnosis based on characteristic lamellar fibrosis, polygonal eosinophilic cells, and positive CK7 and HepPar-1 staining. Confirmatory molecular testing through fusion was not performed. Planned treatment with a combination regimen of nivolumab and neratinib was scheduled; however, the patient deteriorated rapidly, and systemic therapy could not be initiated before death. Through this case and accompanying review, we aim to highlight the diagnostic complexity, molecular underpinnings, and current therapeutic approaches of FLC. This case was notable for advanced peritoneal carcinomatosis at presentation, severe thrombocytosis, and the diagnostic and therapeutic challenges posed by metastatic fibrolamellar carcinoma without molecular confirmation. Taken together, this underscores the importance of early recognition, molecular testing, and coordinated clinical management in optimizing outcomes for this uncommon malignancy. - Source: PubMed
Publication date: 2026/05/06
El Darzi RoyAshy ChristopherKhrayzat AliChahine SallyTawil AymanTemraz Sally - Imidacloprid (IMI), a widely used neonicotinoid insecticide, has been associated with neurotoxic effects; however, the system-level mechanisms underlying these effects remain incompletely understood. Here, we integrated network toxicology with multi-omics analyses to investigate IMI-induced neurotoxicity in SH-SY5Y cells and the whole-organism model, Caenorhabditis elegans (C. elegans). Network toxicology identified 284 potential IMI-related targets, and protein-protein interaction network analysis further prioritized 45 core targets, including HSP90AA1, ESR1, MAPK3, SRC, MAPK1, IL6, BCL2, PRKACA, and MAPK8. Molecular docking suggested potential binding interactions between IMI and several core targets, while qRT-PCR provided transcript-level support for a subset of hub genes. Transcriptomic profiling revealed pronounced model-specific responses. In SH-SY5Y cells, IMI primarily induced neuron-related molecular alterations, characterized by disruption of voltage-gated calcium channel activity and enrichment of multiple synaptic pathways. In contrast, C. elegans exhibited broader organism-level transcriptomic remodeling involving developmental processes, extracellular structure organization, and stress-adaptive pathways, including the MAPK and FoxO signaling pathways. Untargeted metabolomics in SH-SY5Y cells further revealed biochemical remodeling related to the neuroactive ligand-receptor interaction pathway, glutathione metabolism, oxidative phosphorylation, and ABC transporter pathways. In addition, IMI significantly increased intracellular ROS levels and disrupted glutathione redox homeostasis, as reflected by altered GSH and GSSG levels and the GSH/GSSG ratio. Integrated analysis identified neuroactive ligand-receptor interaction and glutathione metabolism as shared pathway-level features across datasets, supporting a mechanistic model in which disruption of receptor-mediated neurotransmission is accompanied by redox imbalance. Overall, this study provides a systems-level view of IMI-induced neurotoxicity and highlights both shared pathway-level features and pronounced model-specific biological responses. - Source: PubMed
Publication date: 2026/05/05
Hou XingangWang KaiHou ZhiguangWei LipingZhang ZhengZheng XiaojiaoWang YuzhenLv MengTian JiangxinWang ZhaoyangMa ChaoZhao FanrongHan Jiajun