Ask about this productRelated genes to: Jph2 antibody
- Gene:
- JPH2 NIH gene
- Name:
- junctophilin 2
- Previous symbol:
- -
- Synonyms:
- JP-2
- Chromosome:
- 20q13.12
- Locus Type:
- gene with protein product
- Date approved:
- 2000-12-08
- Date modifiied:
- 2019-04-23
Related products to: Jph2 antibody
Related articles to: Jph2 antibody
- T-tubules are structural components of the cardiomyocyte plasma membrane that are imperative for efficient excitation-contraction coupling and cardiac contraction. Junctophilin-2 (JPH2) has been postulated in multiple preclinical models to play a key role in T-tubule structure development, maintenance, and organisation by anchoring the sarcoplasmic reticulum to the sarcolemma and maintaining the spatial distance between excitation contraction coupling proteins. Animal studies have shown that JPH2 downregulation leads to T-tubule dysfunction and impaired cardiac contractility, and upregulation of JPH2 has been shown to rescue heart failure in animals, holding therapeutic promise. However, human-level data on JPH2's role in heart failure remain sparse, particularly regarding its protein abundance and functional relevance in human disease, which is imperative for validating therapeutic target selection. In this study, we examined JPH2 protein levels in 152 human samples, including healthy hearts, hearts with cardiovascular risk factors, and failing hearts of various etiologies. We found that JPH2 abundance remains unchanged in human heart failure, despite significant disruption in T-tubule structure and cardiac dysfunction in these patients. Our findings suggest that JPH2 abundance alone is insufficient to preserve T-tubule integrity in failing human hearts and challenge the role of JPH2 in human disease. This work underscores the critical need for human tissue-based models in cardiovascular research, highlighting their potential in bridging preclinical findings to clinical applications. - Source: PubMed
Publication date: 2026/04/17
Pitoulis FotiosPamias-Lopez BlancaBedi KennethCheng LanLee BenjaminAcker MichaelPeyster EliotMargulies KennethProsser BenjaminIbrahim Michael - Vandetanib is a novel multi-targeted tyrosine kinase inhibitor (TKI) that has demonstrated clinical efficacy in the long-term treatment of medullary thyroid carcinoma. However, its use is frequently associated with cardiovascular side effects, some of which may be life-threatening. Notably, multi-targeted TKIs have been increasingly implicated in the risk of cardiotoxicity. Among these, cardiac contractile dysfunction has emerged as a critical concern, yet the underlying mechanisms remain incompletely elucidated-particularly the phenomenon of excitation-contraction uncoupling. This study aims to investigate how vandetanib affects cardiac contractility, with a specific focus on sarcomeric protein degradation, and to identify potential molecular targets for reversing myofilament degradation. Chronic treatment with vandetanib led to a significant reduction in myocardial contractile function, the disruption of cardiac troponin T (cTnT), cardiac troponin I (cTnI) organization and downregulation of essential myofilament proteins, including cTnT (42.3% ± 5.6% protein loss)and MYOM1 (32.7% ± 4.9% protein loss), without notable suppression of calcium-handling proteins such as JPH2, p-PLN, and p-CaMKII. Calcium imaging revealed preserved sarcoplasmic reticulum (SR) calcium release, suggesting contractile dysfunction was not primarily calcium-driven. Instead, reduced myofilament calcium sensitivity and partial sarcomere disassembly were observed. Mechanistically, we identified upregulation of calpain expression and enzymatic overactivation as key mediators of sarcomeric protein degradation. Inhibition of calpain activity partially rescued vandetanib-induced loss of contractile proteins and preserved myofilament structure. Calpain1 overexpression aggravated, while calpain1 knockdown partially rescued, vandetanib-induced cTnT degradation. Our findings uncover a novel mechanism underlying TKI-induced cardiotoxicity, involving calpain-dependent degradation of cardiac myofilament proteins and independent of calcium dysregulation. This study highlights the critical role of sarcomere stability in maintaining cardiac function during TKI therapy and identifies calpain as a promising therapeutic target for cardioprotection, with calpain activation rather than calcium dysregulation being the key driver of vandetanib-induced cardiac dysfunction. - Source: PubMed
Publication date: 2026/02/27
Ji FangHuang JieYan JieLv SiLu LinWen HuLu JianYuan HuanGu YinshanLiao BinWu LinXie BingbinLi Miaoling - Doxorubicin (DOX) induces dose-dependent cardiotoxicity (DIC), which can lead to progressive heart failure and life-threatening arrhythmias. Guizhi Gancao Decoction (GGD), composed of dried twig of Cinnamomum aromaticum Nees (dry weight 12g) and dried roots and rhizomes of Glycyrrhiza uralensis Fisch. ex DC. (dry weight 6g), is a classical formula first recorded by Zhang Zhong-jing in the Shang Han Lun. It has been used for centuries in traditional Chinese medicine (TCM) to treat cardiovascular ailments associated with "heart-yang deficiency". However, its potential efficacy against DIC remains unexplored. - Source: PubMed
Publication date: 2026/02/17
Yao RuixueHuang JiayueShan XiaoliLi RongshanChen HuihuaZhao PeiLu RongZhang Chen - Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease and a leading cause of sudden cardiac death (SCD) in young adults and athletes. It exhibits marked clinical variability, which may be influenced by genetic background and environmental factors. Although is the most frequently implicated gene, data from Latin American and admixed populations remain scarce. In this study, we describe three unrelated Ecuadorian patients with clinically diagnosed HCM who harbored variants. Two patients carried likely pathogenic mutations (p.Glu258Lys and p.His875Profs*8), while novel missense variants (p.Ala536Pro and p.Thr274Met) were identified as variants of uncertain significance (VUS). Additional variants were detected in , , , , , and , but given their classification as VUS or a lack of association with HCM, they are described only as incidental findings. An ancestry analysis revealed heterogeneous contributions of Native American, European, and African backgrounds, reflecting the admixed composition of the Ecuadorian population. This case series underscores the phenotypic heterogeneity of HCM, even among patients with variants, and highlights the importance of genomic testing in underrepresented populations to improve diagnosis, family screening, and SCD risk stratification. - Source: PubMed
Publication date: 2026/01/21
Paz-Cruz EliusGuevara-Ramírez PatriciaTamayo-Trujillo RafaelRuiz-Pozo Viviana ACadena-Ullauri SantiagoIbarra-Castillo RitaLaso-Bayas José LuisMeza-Chico LeonelCabrera-Andrade AlejandroZambrano Ana Karina - Patients receiving doxorubicin (DOX) chemotherapy are susceptible to cardiac and brain tissue damage, with oxidative stress (OS) as the primary mechanism of injury. The purpose of this research is to identify effective agents to reduce the level of DOX-induced OS in the heart and brain through bioinformatics and in vitro. - Source: PubMed
Publication date: 2026/01/23
Zeng XianghuiZeng QingfengLuo QiLuo Jianping