Apoptosis最新文献

Object

Acute myocardial infarction (AMI) is a serious cardiovascular disease for which there are still no effective therapeutic options available, and melanoma-associated antigen-A13 (Magea13), a member of the MAGE superfamily, has an unknown role in AMI. This study aims to investigate the potential role and molecular mechanisms of Magea13 in myocardial injury associated with AMI through in vivo and in vitro experiments.

Methods

Firstly, differentially expressed genes (DEGs) and signaling pathways were screened by RNA sequencing. Cardiac-specific Magea13 overexpression was achieved with the adeno-associated virus type 9 serotype system. Subsequently, these rats underwent left anterior descending coronary artery (LAD) ligation, followed by histopathological examination, biochemical assay, and Western blot analysis to evaluate the efficacy and feasibility of Magea13 in AMI. Meanwhile, the Magea13-overexpressing rat cardiomyocyte cell line (H9c2) was also subjected to hypoxia-glucose deficiency/reperfusion to mimic AMI injury to further validate its effects in vitro.

Results

The cardiomyocyte-specific overexpression of Magea13 was observed to attenuate myocardial injury in rats with acute myocardial infarction. Furthermore, Magea13 overexpression was demonstrated to attenuate OGD/R-induced H9c2 cell injury. Mechanistic studies have suggested that the protective effect of Magea13 may be mediated through the cAMP-PKA pathway.

Conclusion

Magea13 has been demonstrated to offer protection against AMI myocardial injury through the cAMP-PKA signaling pathway and is therefore a promising therapeutic and predictive target for AMI myocardial injury.

Peritoneal metastasis (PM) is the primary site of distant metastasis in gastric cancer (GC) and is associated with an advanced disease stage and poor prognosis. Due to its high resistance to chemotherapy, disseminated peritoneal lesions are often untreatable. A primary reason for therapy resistance in cancer cells is often their defective cell death execution mechanisms. Ferroptosis, a newly identified type of regulated cell death, is strongly linked to the emergence and formation of tumors. Earlier studies have demonstrated the significant role of RNA-binding proteins in ferroptosis. Nevertheless, the fundamental process linking Staufen Double-Stranded RNA Binding Protein 1 (STAU1) to ferroptosis in the peritoneal metastasis of gastric cancer is yet to be clarified. This study shows that the RNA-binding protein STAU1 is crucial for regulating ferroptosis in gastric cancer cells. Elevated levels of STAU1 are linked to unfavorable outcomes in individuals diagnosed with gastric cancer. STAU1 was up-regulated by PLAGL2 and decreased the stability of NCOA4 mRNA by binding to the 3ʹ-untranslated region. Decreased NCOA4 expression inhibits the accumulation of reactive iron, the occurrence of the Fenton reaction, and cellular ROS generation in the GC cells. Additionally, we showed that NCOA4 is crucial in the process of ferritinophagy triggered by the reduction of STAU1 in gastric cancer cells. Ultimately, the process safeguards GC cells from ferroptosis. These findings elucidate the function of PLAGL2/STAU1/NCOA4 in the ferroptosis of gastric cancer cells and provide theoretical backing for possible diagnostic markers and treatment targets for peritoneal metastasis in gastric cancer.

The human body to prolonged high-altitude environments exposure can cause the decreased hepcidin and the disorder of iron homeostasis. Few animal studies have examined the molecular basis of iron metabolism disorder and the impact of hepcidin on the complex phenotype of high-altitude environments. In this study, we display reduced hepcidin level and impaired iron homeostasis upon hypobaric hypoxia, accompanied by mitochondrial dysfunction, abnormal blood cells and metabolic disorder. Importantly, mice overexpressing hepcidin show resistance to hypoxia-induced mitochondrial injury in liver and improve the body homeostasis. The comprehensive characterization of the metabolic pathways analysis demonstrates the porphyrin metabolism modulated by hepcidin may play a significant role in improving blood cell abnormalities upon high altitude hypoxia. In addition, hepcidin transcription is inhibited by histone modification and interruption of SMAD signaling pathway in hepatocytes in response to hypoxic stress to decrease hepcidin level. Our data highlight the key role of hepcidin in regulating the complex phenotype of high-altitude environments by altered metabolic and mitochondrial function. These results provide a theoretical reference to understanding the role of hepcidin in maintaining physiological function in high altitude, thus assisting in the development of strategies to better prevent and alleviate imbalance of energy homeostasis and adverse effects.

Humans can perceive five canonical tastes: salty, sour, umami, sweet, and bitter. These tastes are transmitted through the activation of ion channels and receptors. Bitter taste receptors (Taste Family 2 Receptors; T2Rs) are a sub-family of 25 G-protein coupled receptor (GPCR) isoforms that were first identified in type II taste bud cells. T2Rs are activated by a broad array of bitter agonists, which cause an increase in intracellular calcium (Ca²⁺) and a decrease in cyclic adenosine 3’,5’-monophosphate (cAMP). Interestingly, T2Rs are expressed beyond the oral cavity, where they play diverse non-taste roles in cell physiology and disease. Here, we summarize the literature that explores the role of T2Rs in apoptosis. Activation of T2Rs with bitter agonists induces apoptosis in several cancers, the airway epithelia, smooth muscle, and more. In many of these tissues, T2R activation causes mitochondrial Ca²⁺ overload, a main driver of apoptosis. This response may be a result of T2R cellular localization, nuclear Ca²⁺ mobilization and/or a remnant of the established immunological roles of T2Rs in other cell types. T2R-induced apoptosis could be pharmacologically leveraged to treat diseases of altered cellular proliferation. Future work must explore additional extra-oral T2R-expressing tissues for apoptotic responses, develop methods for in-vivo studies, and discover high affinity bitter agonists for clinical application.