ABSTRACT
INTRODUCTION: Although oxidative stress has been demonstrated to mediate acute ethanol-induced changes in autophagy in the heart, the precise mechanism behind redox regulation in acute ethanol heart disease remains largely unknown. METHODS: Wild-type C57BL/6 mice were intraperitoneally injected with ethanol (3 g/kg/day) for 3 consecutive days. The effects of ethanol on cultured primary cardiomyocytes and H9c2 myoblasts were also studied in vitro. Levels of autophagic flux, cardiac apoptosis and function, reactive oxygen species (ROS) accumulation, NOX4, and NOX2 were examined. The NOX4 gene was knocked down with NOX4 siRNA. RESULTS: In this study, we demonstrated that schisandrin B inhibited acute ethanol-induced autophagy and sequent apoptosis. In addition, schisandrin B treatment improved cardiac function in ethanol-treated mice. Furthermore, NOX4 protein expression was increased during acute ethanol exposure, and the upregulation of NOX4 was significantly inhibited by schisandrin B treatment. The knockdown of NOX4 prevented ROS accumulation, cell autophagy, and apoptosis. CONCLUSION: These results highlight that NOX4 is a critical mediator of ROS and elaborate the role of the NOX4/ROS axis in the effect of schisandrin B on autophagy and autophagy-mediated apoptosis in acute ethanol exposure, which suggests a therapeutic strategy for acute alcoholic cardiomyopathy.
Subject(s)
Autophagy/drug effects , Cardiomyopathy, Alcoholic/prevention & control , Heart Injuries/prevention & control , Lignans/pharmacology , NADPH Oxidase 4/metabolism , Polycyclic Compounds/pharmacology , Protective Agents/pharmacology , Animals , Apoptosis/drug effects , Autophagy/genetics , Cyclooctanes/pharmacology , Cyclooctanes/therapeutic use , Down-Regulation , Ethanol/toxicity , Gene Knockdown Techniques , Heart Injuries/chemically induced , Heart Injuries/metabolism , Lignans/therapeutic use , Male , Mice, Inbred C57BL , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/pathology , NADPH Oxidase 4/antagonists & inhibitors , NADPH Oxidase 4/genetics , Polycyclic Compounds/therapeutic use , Primary Cell Culture , Protective Agents/therapeutic use , Reactive Oxygen Species/antagonists & inhibitors , Reactive Oxygen Species/metabolism , Signal Transduction/drug effectsABSTRACT
Lung cancer is a common malignant neoplasm that is prone to distant metastasis. Gastrointestinal metastasis from lung cancer is rather rare no matter what stage. Herein, we presented a case of pulmonary adenocarcinoma six months after thoracoscopic Lobectomy isolated metastasis to sigmoid colon. Then the patient underwent radical resection of metastatic tumors of sigmoid colon. The pathologic morphology and immunohistochemistry of lung adenocarcinoma is highly consistent with the sigmoid colon tumor and their gene profiles are likely similar expect for an AXIN1 mutation in primary tumor and not in the metastatic lesion.
