Serine-threonine Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is the key component in noncanonical Wnt5a signaling and has been shown to regulate its signaling. In this study, we found that CaMKII induced by Wnt5a remarkably reduced the protein stability of the silencing mediator of retinoic acid and thyroid hormone receptor (SMRT), a co-repressor of Notch signaling, through proteasomal degradation. Wnt5a was found to enhance Notch1 intracellular domain (Notch1-IC) transcription activity, which could be inhibited by treatment with KN93, a CaMKII inhibitor. The kinase activity of CaMKII was essential for the activation of Notch signaling. We also determined that CaMKII could enhance the association between Notch1-IC and RBP-Jk. Furthermore, the physical association between RBP-Jk and SMRT was substantially suppressed by CaMKII. We demonstrated that CaMKII directly bound and phosphorylated SMRT at Ser-1407, thereby facilitating SMRT translocation from the nucleus to the cytoplasm and proteasome-dependent degradation. These results suggest that CaMKII down-regulated the protein stability of SMRT through proteasomal degradation.
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http://dx.doi.org/10.1074/jbc.M112.356048 | DOI Listing |
Sleep Breath
January 2025
Nantong Key Laboratory of Translational Medicine in Cardiothoracic Diseases, and Research Institution of Translational Medicine in Cardiothoracic Diseases, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, China.
Background: Our previous study have demonstrated chronic intermittent hypoxia (CIH) induced cardiomyocyte apoptosis and cardiac dysfunction. However, the molecular mechanisms are complicated and varied. In this study, we first investigated the CaMKIIγ expression and signaling pathway in the pathogenesis of cardiomyocyte apoptosis after CIH.
View Article and Find Full Text PDFFASEB J
January 2025
Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
Sarcopenia is an age-related muscle atrophy syndrome characterized by the loss of muscle strength and mass. Although many agents have been used to treat sarcopenia, there are no successful treatments to date. In this study, we identified Danshensu sodium salt (DSS) as a substantial suppressive agent of muscle atrophy.
View Article and Find Full Text PDFNeuronal excitation-transcription (E-T) coupling pathways can be initiated by local increases of Ca concentrations within a nanodomain close to the L-type voltage-gated Ca channel (LTCC). However, molecular mechanisms controlling LTCC organization within the plasma membrane that help creation these localized signaling domains remain poorly characterized. Here, we report that neuronal depolarization increases Ca 1.
View Article and Find Full Text PDFJ Ethnopharmacol
January 2025
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China. Electronic address:
Ethnopharmacological Relevance: Di Dang Tang is a classic formula from Shang Han Lun, originally used to treat conditions such as blood stasis and heat accumulation. It is widely applied in the treatment of diabetes and its complications, but its effects on Type 2 Diabetes Mellitus-related Cognitive Dysfunction (T2DM-CD) remain unclear.
Aim Of The Study: The study aimed to investigate the metabolic characteristics of patients with T2DM-CD.
PLoS One
January 2025
Department of Cardiovascular Sciences, Anaesthesia, Critical Care and Pain Management, University of Leicester, Leicester, United Kingdom.
Sustained pathologic myocardial hypertrophy can result in heart failure(HF); a significant health issue affecting a large section of the population worldwide. In HF there is a marked elevation in circulating levels of the peptide urotensin II(UII) but it is unclear whether this is a result of hypertrophy or whether the high levels contribute to the development of hypertrophy. The aim of this study is to investigate a role of UII and its receptor UT in the development of cardiac hypertrophy and the signalling molecules involved.
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