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Beclin-1 1

丹参酮IIA 1

细胞凋亡 1

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lncR-GAS5 upregulates the splicing factor to impair endothelial autophagy, leading to atherogenesis

《医学前沿（英文）》 2023年第17卷第2期页码 317-329 doi: 10.1007/s11684-022-0931-4

摘要： Long noncoding RNAs (lncRNAs) play a critical role in the regulation of atherosclerosis. Here, we investigated the role of the lncRNA growth arrest-specific 5 (lncR-GAS5) in atherogenesis. We found that the enforced expression of lncR-GAS5 contributed to the development of atherosclerosis, which presented as increased plaque size and reduced collagen content. Moreover, impaired autophagy was observed, as shown by a decreased LC3II/LC3I protein ratio and an elevated P62 level in lncR-GAS5-overexpressing human aortic endothelial cells. By contrast, lncR-GAS5 knockdown promoted autophagy. Moreover, serine/arginine-rich splicing factor 10 (SRSF10) knockdown increased the LC3II/LC3I ratio and decreased the P62 level, thus enhancing the formation of autophagic vacuoles, autolysosomes, and autophagosomes. Mechanistically, lncR-GAS5 regulated the downstream splicing factor SRSF10 to impair autophagy in the endothelium, which was reversed by the knockdown of SRSF10. Further results revealed that overexpression of the lncR-GAS5-targeted gene miR-193-5p promoted autophagy and autophagic vacuole accumulation by repressing its direct target gene, SRSF10. Notably, miR-193-5p overexpression decreased plaque size and increased collagen content. Altogether, these findings demonstrate that lncR-GAS5 partially contributes to atherogenesis and plaque instability by impairing endothelial autophagy. In conclusion, lncR-GAS5 overexpression arrested endothelial autophagy through the miR-193-5p/SRSF10 signaling pathway. Thus, miR-193-5p/SRSF10 may serve as a novel treatment target for atherosclerosis.

关键词： lncR-GAS5 miR-193-5p splicing factor SRSF10 autophagy atherogenesis

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The critical role of autophagy in plant responses to abiotic stresses

Yu WANG,Jie ZHOU,Jingquan YU

《农业科学与工程前沿（英文）》 2017年第4卷第1期页码 28-36 doi: 10.15302/J-FASE-2017130

摘要： Autophagy is an evolutionary conserved recycling process in eukaryotes whereby intracellular components are engulfed by autophagosomes, which are subsequently transferred to the vacuoles for further degradation and reuse. In organisms like yeast and metazoans, autophagy is actively engaged during environmental perturbation either by degrading denatured proteins and organelles or by interfacing with stress related signaling molecules. Studies over the last decade have also revealed numerous important mechanisms where autophagy is widely involved in plant abiotic stress responses. Autophagy serves as a pivotal route for nutrient remobilization by the degradation of superfluous or damaged cellular cytoplasmic material and organelles. It is also reported to regulate the accumulation of reactive oxygen species, to maintain the cellular redox balance of plants under stressful conditions. Furthermore, autophagy is essential in regulating cellular toxicity by removing aggregated and/or denatured proteins and thereby improving plant stress tolerance. In this review, recent advances in our understanding of autophagy, along with pathways and regulatory networks through which it influences many aspects of plant growth and development in response to nutrient starvation, oxidative stress, osmotic stress and extreme temperatures are discussed.

关键词： abiotic stresses autophagy extreme temperature nutrient starvation osmotic stress oxidative stress

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Autophagy and the nutritional signaling pathway

Long HE,Shabnam ESLAMFAM,Xi MA,Defa LI

《农业科学与工程前沿（英文）》 2016年第3卷第3期页码 222-230 doi: 10.15302/J-FASE-2016106

摘要： During their growth and development, animals adapt to tremendous changes in order to survive. These include responses to both environmental and physiological changes and autophagy is one of most important adaptive and regulatory mechanisms. Autophagy is defined as an autolytic process to clear damaged cellular organelles and recycle the nutrients via lysosomic degradation. The process of autophagy responds to special conditions such as nutrient withdrawal. Once autophagy is induced, phagophores form and then elongate and curve to form autophagosomes. Autophagosomes then engulf cargo, fuse with endosomes, and finally fuse with lysosomes for maturation. During the initiation process, the ATG1/ULK1 (unc-51-like kinase 1) and VPS34 (which encodes a class III phosphatidylinositol (PtdIns) 3-kinase) complexes are critical in recruitment and assembly of other complexes required for autophagy. The process of autophagy is regulated by autophagy related genes (ATGs). Amino acid and energy starvation mediate autophagy by activating mTORC1 (mammalian target of rapamycin) and AMP-activated protein kinase (AMPK). AMPK is the energy status sensor, the core nutrient signaling component and the metabolic kinase of cells. This review mainly focuses on the mechanism of autophagy regulated by nutrient signaling especially for the two important complexes, ULK1 and VPS34.

关键词： Autophagy ULK1 complex VPS34 complex AMPK mTOR nutrient signaling

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Autoimmune regulator regulates autophagy in THP-1 human monocytes

Liang SHI, Li-Hua HU, Yi-Rong LI

《医学前沿（英文）》 2010年第4卷第3期页码 336-341 doi: 10.1007/s11684-010-0096-4

摘要： The autoimmune regulator (AIRE) is a crucial factor for the induction of central tolerance, and mutations in this gene lead to abnormal immune responses. However, the role of AIRE in autophagy in immune cells, especially in monocytes, is obscure. In the present study, we found that overexpression of AIRE in THP-1 human monocytes resulted in increased endogenous light chain 3 (LC3)-II level and elevated LC3 positive vesicles. Moreover, an autophagy inhibitor or knockdown of AIRE by small interference RNA attenuated these effects. In contrast, the expression of p62/SQSTM1 remained unchanged in THP-1 cells after the corresponding treatment. Our findings indicate that AIRE plays a role in the regulation of autophagy in THP-1 human monocytes.

关键词： autoimmune regulator autophagy monocytes light chain 3 (LC3)

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Superenhancers activate the autophagy-related genes Beclin1 and LC3B to drive metastasis and drug resistance

《医学前沿（英文）》 2022年第16卷第6期页码 883-895 doi: 10.1007/s11684-022-0919-0

摘要： Metastasis and drug resistance are the leading causes of poor prognosis in patients with osteosarcoma. Identifying the relevant factors that drive metastasis and drug resistance is the key to improving the therapeutic outcome of osteosarcoma. Here, we reported that autophagy was highly activated in metastatic osteosarcoma. We found increased autophagolysosomes in metastatic osteosarcoma cell lines by using electron microscopy, Western blot, and immunofluorescence experiments. We further examined the expression of the autophagy-related genes Beclin1 and LC3B in 82 patients through immunohistochemistry and found that Beclin1 and LC3B were highly related to unfavorable prognosis of osteosarcoma. Knockdown of Beclin1 and LC3B reduced invasion, metastasis, and proliferation in metastatic osteosarcoma cells. In vitro and in vivo studies also demonstrated that inhibiting by 3-MA inhibited cell growth and metastasis. Moreover, we demonstrated that autophagy-related genes were activated by SEs and that the inhibition of SEs by JQ-1 decreased the metastasis of osteosarcoma. Overall, our findings highlighted the association of autophagy with osteosarcoma progression and shed new light on autophagy-targeting therapy for osteosarcoma.

关键词： osteosarcoma autophagy metastasis drug resistance Beclin1 LC3B

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Resveratrol reduces intracellular reactive oxygen species levels by inducing autophagy through the AMPK-mTOR

Jun Song, Yeping Huang, Wenjian Zheng, Jing Yan, Min Cheng, Ruxing Zhao, Li Chen, Cheng Hu, Weiping Jia

《医学前沿（英文）》 2018年第12卷第6期页码 697-706 doi: 10.1007/s11684-018-0655-7

摘要：

Oxidative stress induced by free fatty acid aggravates endothelial injury, which leads to diabetic cardiovascular complications. Reduction of intracellular oxidative stress may attenuate these pathogenic processes. The dietary polyphenol resveratrol reportedly exerts potential protective effects against endothelial injury. This study determined whether resveratrol can reduce the palmitic acid (PA)-induced generation of reactive oxygen species (ROS) and further explored the underlying molecular mechanisms. We found that resveratrol significantly reduced the PA-induced endothelial ROS levels in human aortic endothelial cells. Resveratrol also induced endothelial cell autophagy, which mediated the effect of resveratrol on ROS reduction. Resveratrol stimulated autophagy via the AMP-activated protein kinase (AMPK)-mTOR pathway. Taken together, these data suggest that resveratrol prevents PA-induced intracellular ROS by autophagy regulation via the AMPK-mTOR pathway. Thus, the induction of autophagy by resveratrol may provide a novel therapeutic candidate for cardioprotection in metabolic syndrome.

关键词： resveratrol reactive oxygen species AMPK mTOR autophagy

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Increased expression of coronin-1a in amyotrophic lateral sclerosis: a potential diagnostic biomarker and therapeutic target

《医学前沿（英文）》 2022年第16卷第5期页码 723-735 doi: 10.1007/s11684-021-0905-y

摘要： Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. At present, no definite ALS biomarkers are available. In this study, exosomes from the plasma of patients with ALS and healthy controls were extracted, and differentially expressed exosomal proteins were compared. Among them, the expression of exosomal coronin-1a (CORO1A) was 5.3-fold higher than that in the controls. CORO1A increased with disease progression at a certain proportion in the plasma of patients with ALS and in the spinal cord of ALS mice. CORO1A was also overexpressed in NSC-34 motor neuron-like cells, and apoptosis, oxidative stress, and autophagic protein expression were evaluated. CORO1A overexpression resulted in increased apoptosis and oxidative stress, overactivated autophagy, and hindered the formation of autolysosomes. Moreover, CORO1A activated Ca²⁺-dependent phosphatase calcineurin, thereby blocking the fusion of autophagosomes and lysosomes. The inhibition of calcineurin activation by cyclosporin A reversed the damaged autolysosomes. In conclusion, the role of CORO1A in ALS pathogenesis was discovered, potentially affecting the disease onset and progression by blocking autophagic flux. Therefore, CORO1A might be a potential biomarker and therapeutic target for ALS.

关键词： amyotrophic lateral sclerosis coronin-1a autophagy pathogenesis

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丹参酮IIA通过Beclin-1介导的自噬性凋亡抑制非小细胞肺癌 Article

白莎莎, 崔赛男, 温文浩, 梁丽娴, 白静, 林慧媛, 崔永飞, 杨蕾, 刘中秋, 郑远, 张荣

《工程（英文）》 2022年第19卷第12期页码 128-138 doi: 10.1016/j.eng.2021.07.014

摘要：

肺癌是癌症死亡的主要原因，因此有必要制定一种新的治疗策略。丹参酮IIA（Tan IIA）是常用中药丹参的一种有效成分，为开发治疗肺癌的新策略提供了新方向。Tan IIA 在体外和体内均可通过诱导自噬性细胞凋亡从而抑制肺癌。Tan IIA 在人类非小细胞肺癌（NSCLC）细胞系中增加凋亡细胞以及剪切型-半
胱氨酸天冬氨酸蛋白水解酶（cleaved caspase）3 和cleaved caspase 9 的表达，降低B淋巴细胞瘤（Bcl-2）与Bcl-2 相关X蛋白（Bax）的比值；自噬激活剂雷帕霉素可促进此过程，而自噬抑制剂3-甲基腺嘌呤（3-MA）减弱此作用。Tan IIA 诱导更多的自噬体，上调轻链3β（LC-3B）I 和LC-3B II，减少螯合体1（SQSTM1/p62）的表达，caspase 3 拮抗剂未能减弱此作用。此外，LC-3B基因（LC3B）过表达和白噬基因5（ATG-5）下调细胞株的实验结果进一步证实Tan IIA 诱导NSCLC细胞发生了自噬相关调亡。过表达和沉默Beclin-1都明显减弱Tan IIA 的作用，提示Tan IIA 诱导的自噬相关调亡依赖于Beclin-1。总之，研究证明Tan IIA是一种潜在的新的抗癌治疗选择。

关键词：丹参酮IIA 自噬细胞凋亡 Beclin-1