检索结果-南通市图书馆

Amiodarone induces autophagy/mitophagy by activating sirtuin-3 in acute myelocytic leukemia

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

中国药理学与毒理学杂志 2019年第10期 778-779页

作者： ZHANG Jin SUN De-juan ZHANG Lan OU Yang-liang State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University School of Life Science and Engineering Southwest Jiaotong University

OBJECTIVE To find a new treatment strategy foracute myelocytic leukemia(AML), we tried to find new targets. Sirtuin-3(SIRT3), a NAD+-dependent protein deacetylase localized primarily in the mitochondrion,is well-known to regulate autophagy, which is an evolutionarily conserved, multi-step lysosomal degradation process and also implicated in many diseases, such as AML.Accumulating evidence has revealed that SIRT3 may act as a tumor suppressor in AML, and thus activating SIRT3 will represent a potential therapeutic avenue.METHODS Aotophagy related protein expression and SIRT3 were analyzed by The Cancer Genome Atlas(TCGA)analysis. SIRT3 activator was selected by using in silico screening and anti-proliferative activities. The target selectivity of amiodarone was determined by co-crystal structure and deacetylase activity assays. The mechanisms of amiodarone-induced autophagy/mitophagy were investigated by fluorescence microscope, Western blotting, flow cytometry analysis, immunocytochemistry, as well as i TRAQ-based proteomics analysis. The therapeutic effect of amiodarone was assessed by xenograft AML mouse model. RESULTS TCGA dataset, we identified that SIRT3 was a key prognostic factor in AML, which was closely associated with the survival of patients. Subsequently, we computationally and experimentally screened a series of candidate activators of SIRT3 from Drugbank,and found the best candidate compound amiodarone,which was further validated by co-crystal structure of SIRT3/amiodarone. Interestingly, amiodarone induced autophagy via SIRT3-mediated AMPK-m TOR-ULK1-Beclin-1 pathway in U937 and HL-60 cells. Moreover,this activator induced mitophagy via SIRT3-deacetylating FOXO3 a and thus triggering PINK1/Parkin pathway in AML cells. The i TRAQ-based proteomics analyses revealed that amiodarone induced mitophagy by downregulating 14-3-3γ, upregulating and deacetylating Beclin-1,as well as activating FOXO3 a-HIF1α-BNIP3 and VDAC1.What is more, deacetylation proteomics analyses revealed that amiodarone could activat

关键词： amiodarone sirtuin-3 activator autophagy mitophagy acute myelocytic leukemia

Folic acid-induced animal model of kidney disease

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Animal Models and Experimental Medicine 2021年第4期4卷 329-342页

作者： Liang-Jun Yan Department of Pharmaceutical Sciences College of PharmacyUniversity of North Texas Health Science CenterFort WorthTexasUSA

The kidneys are a vital organ that is vulnerable to both acute kidney injury(AKI)and chronic kidney disease(CKD)which can be caused by numerous risk factors such as ischemia,sepsis,drug toxicity and drug overdose,exposure to heavy metals,and diabetes.In spite of the advances in our understanding of the pathogenesis of AKI and CKD as well AKI transition to CKD,there is still no available therapeutics that can be used to combat kidney disease effectively,highlighting an urgent need to further study the pathological mechanisms underlying AKI,CKD,and AKI progression to CKD.In this regard,animal models of kidney disease are indispensable.This article reviews a widely used animal model of kidney disease,which is induced by folic acid(FA).While a low dose of FA is nutritionally beneficial,a high dose of FA is very toxic to the kidneys.Following a brief description of the procedure for disease induction by FA,major mechanisms of FA-induced kidney injury are then reviewed,including oxidative stress,mitochondrial abnormalities such as impaired bioenergetics and mitophagy,ferroptosis,pyroptosis,and increased expression of fibroblast growth factor 23(FGF23).Finally,application of this FA-induced kidney disease model as a platform for testing the efficacy of a variety of therapeutic approaches is also discussed.Given that this animal model is simple to create and is reproducible,it should remain useful for both studying the pathological mechanisms of kidney disease and identifying therapeutic targets to fight kidney disease.

关键词： acute kidney injury chronic kidney disease ferroptosis fibroblast growth factor 23 folic acid mitochondria mitophagy oxidative stress pyroptosis

维普期刊数据库

Multitasking guardian of mitochondrial quality:Parkin function and Parkinson’s disease

在线全文

学校读者我要写书评

暂无评论

Translational Neurodegeneration 2021年第1期10卷 40-57页

作者： Iryna Kamienieva Jerzy Duszynski Joanna Szczepanowska Nencki Institute of Experimental Biology Polish Academy of Science02-093 WarsawPoland

The familial form of Parkinson's disease(PD)is linked to mutations in specific genes.The mutations in parkin are one of the most common causes of early-onset PD.Mitochondrial dysfunction is an emerging active player in the pathology of neurodegenerative diseases,because mitochondria are highly dynamic structures integrated with many cellular functions.Herein,we overview and discuss the role of the parkin protein product,Parkin E3 ubiquitin ligase,in the cellular processes related to mitochondrial function,and how parkin mutations can result in pathology in vitro and in vivo.

关键词： Mitochondria Parkinson's disease Parkin PINK1 mitophagy Parkin mutations

Effect of active components group of Xiaoxuming decoction on cerebral mitophagy after focal cerebral ischemia/reperfusion injury

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

中国药理学与毒理学杂志 2019年第10期 841-842页

作者： BAI Xue DU Xiao HE Xiao-li Institute of Medicinal Plant Development Chinese Academy of Medical Sciences and Peking Union Medical College

OBJECTIVE To explore the effect of the active components group of Xiaoxuming decoction(XXMD)on mitophagy after cerebral ischemia/reperfusion(I/R) in MCAO rats. METHODS Male Sprague-Dawley rats were randomly divided into 4 groups: sham group, XXMD and rapamycin group. The I/R models were induced by middle cerebral artery occlusion. The effects of XXMD and rapamycin on behavioral study of focal cerebral I/R in rats were measured by Zea-Longa′ s level standard scoring method and neurological defect score(m NSS). The volume percentage and hemispheric swelling of rat cerebral infarction were detected by TTC staining. Proteins in the mitophagy were detected by Western blotting. RESULTS The behavioral results showed that compared with the model group, XXMD decoction and rapamycin could significantly alleviate the neurological deficit scores after I/R, decreased the m NSS score(Pmitophagy were activated at 24 h after cerebral I/R, and then it was inhibited. XXMD can protect mitochondrial structures, regulate the level of mitophagy at different points after cerebral I/R, inhibit the excessive activation of mitophagy in 24 h after I/R, and improve the level of mitophagy in the later stage of I/R.

关键词： active components Xiaoxuming decoction cerebral ischemic reperfusion mitochondrial function mitophagy

mitophagy in the Skeletal Muscle Is Suppressed in Spleen Qi Deficiency

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Chinese Medicine 2019年第1期10卷 11-18页

作者： Dan Ma Wenjun Liu Lu Wang Xinzhu Xu Lingzhi Wang Huaxin Yu Xudong Liu Huihui Liu Deshan Wang Dehong Shan School of Basic Medicine Liaoning University of Traditional Chinese Medicine Shenyang China Teaching and Experimental Center Liaoning University of Traditional Chinese Medicine Shenyang China

Objective: Mitochondrial impairment in the skeletal muscle contributes to useless of limbs in spleen qi deficiency;however the genesis of such impairment is not clear. Herein, PTEN-induced putative kinase 1 (PINK1)-Parkin pathway and mitophagy were studied to explore the machinery of mitochondrial impairment. Methods: 16 male SD rats were randomly divided in the control group and spleen qi deficiency group (model group);transmission electron microscope was used to observe mitochondrial morphology;mitochondrial oxidative phosphorylation was assessed by testing mitochondrial membrane potential (MMP) and levels of ATP and ROS;western blot was used to analyze expressions of PINK1, Parkin, microtubule-associated protein 1 light chain 3-II (LC3-II) and p62. Results: Compared with those in the control group, mitochondria became small, less and scattered, MMP and the ATP level were reduced, the ROS level was elevated, PINK1 expression was decreased, p62 expression was increased, but Parkin and LC3-II expressions were not altered, in the model group. Conclusions: Suppression of mitophagy might be related to the mitochondrial damage in the skeletal muscle when spleen qi deficiency develops.

关键词： Spleen Qi Deficiency mitophagy PINK1 Parkin LC3 p62 Muscle

Functional implications of mitochondrial reactive oxygen species generated by oncogenic viruses

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Frontiers in Biology 2014年第6期9卷 423-436页

作者： Young Bong CHOI Edward William HARHAJ Department of Oncology Sidney Kimmel Comprehensive Cancer Center Johns Hopkins School of Medicine Baltimore MD 21287 USA

Between 15% and 20% of human cancers are associated with infection by oncogenic viruses. Oncogenic viruses, including HPV, HBV, HCV and HTLV-1, target mitochondria to influence cell proliferation and survival. Oncogenic viral gene products also trigger the production of reactive oxygen species which can elicit oxidative DNA damage and potentiate oncogenic host signaling pathways. Viral oncogenes may also subvert mitochondria quality control mechanisms such as mitophagy and metabolic adaptation pathways to promote virus replication. Here, we will review recent progress on viral regulation of mitophagy and metabolic adaptation and their roles in viral oncogenesis.

关键词： mitochondria mitophagy virus ROS oncogenes

Autophagy in liver diseases

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Hepatology 2021年第1期13卷 6-65页

作者： Elias Kouroumalis Argryro Voumvouraki Aikaterini Augoustaki Dimitrios N Samonakis Liver Research Laboratory University of Crete Medical SchoolHeraklion 71110Greece 1^st Department of Internal Medicine AHEPA University HospitalThessaloniki 54636Greece Department of Gastroenterology and Hepatology University Hospital of CreteHeraklion 71110Greece

Autophagy is the liver cell energy recycling system regulating a variety of homeostatic mechanisms.Damaged organelles,lipids and proteins are degraded in the lysosomes and their elements are re-used by the cell.Investigations on autophagy have led to the award of two Nobel Prizes and a health of important reports.In this review we describe the fundamental functions of autophagy in the liver including new data on the regulation of autophagy.Moreover we emphasize the fact that autophagy acts like a two edge sword in many occasions with the most prominent paradigm being its involvement in the initiation and progress of hepatocellular carcinoma.We also focused to the implication of autophagy and its specialized forms of lipophagy and mitophagy in the pathogenesis of various liver diseases.We analyzed autophagy not only in well studied diseases,like alcoholic and nonalcoholic fatty liver and liver fibrosis but also in viral hepatitis,biliary diseases,autoimmune hepatitis and rare diseases including inherited metabolic diseases and also acetaminophene hepatotoxicity.We also stressed the different consequences that activation or impairment of autophagy may have in hepatocytes as opposed to Kupffer cells,sinusoidal endothelial cells or hepatic stellate cells.Finally,we analyzed the limited clinical data compared to the extensive experimental evidence and the possible future therapeutic interventions based on autophagy manipulation.

关键词： Autophagy Lipophagy mitophagy Fatty liver disease Fibrosis Liver sinusoidal cells

Human survival and immune mediated mitophagy in neuroplasticity disorders

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Neural Regeneration Research 2019年第4期14卷 735-735页

作者： Ian James Martins Centre of Excellence in Alzheimer’s Disease Research and Care Sarich Neuroscience Research Institute Edith Cowan University School of Psychiatry and Clinical Neurosciences The University of Western Australia McCusker Alzheimer’s Research Foundation Hollywood Medical Centre

Dear editors,Neurodegenerative diseases are now associated with the global obesity and diabetes epidemic in the developing and developed world.Neurodegenerative diseases are a heterogeneous group of disorders with complex factors such as neurohumoral,endocrine and environmental factors involved in induction of these neurodegenerative diseases.The future of science and medicine in neurodegenerative diseases is now dependent on nutritional genomics with insulin resistance a major factor in the induction of neurodegenerative diseases.Nutritional genomics now involves the anti-aging gene Sirtuin 1(Sirt 1)that is important to the prevention of insulin resistance with its critical involvement in the immune system(Martins,2018a,b).Sirt 1 inactivation leads to toxic immune reactions connected to the acceleration of neuron death in various communities.Appetite control with relevance to immunometabolism has become of critical importance to the treatment of neurodegeneration(Figure 1).Nutritional diets activate the heat shock gene Sirt 1 to prevent the increase in heat shock proteins connected to autoimmune disease,mitophagy(Martins,2018a,b)and irreversible programmed cell death in global populations(Figure 1).

关键词： Human survival immune mediated mitophagy neuroplasticity disorders

维普期刊数据库

Nanoscale monitoring of mitochondria and lysosome interactions for drug screening and discover

在线全文

学校读者我要写书评

暂无评论

Nano Research 2019年第5期12卷 1009-1015页

作者： Qixin Chen Xintian Shao Zhiqi Tian Yang Chen Payel Mondal Fei Liu Fengshan Wang Peixue Ling Weijiang He Kai Zhang Zijian Guo Jiajie Diao School of Pharmaceutical Sciences Shandong UniversityJinan 250101China Shandong Academy of Pharmaceutical Science Key Laboratory of BiopharmaceuticalsEngineering Laboratory of Polysaccharide DrugsNational-Local Joint Engineering Laboratory of Polysaccharide DrugsJinan 250101China Department of Cancer Biology University of Cincinnati College of MedicineCincinnatiOH 45267USA Department of Biochemistry University of Illinois at Urbana-ChampaignUrbanaIL 61801USA State Key Laboratory of Coordination Chemistry Coordination Chemistry InstituteSchool of Chemistry and Chemical EngineeringNanjing University Nanjing 210093China

Technology advances in genomics,proteomics,and metabolomics largely expanded the pool of potential therapeutic targets.Compared with the in vitro setting,cell-based screening assays have been playing a key role in the processes of drug discovery and development.Besides the commonly used strategies based on colorimetric and cell viability,we reason that methods that capture the dynamic cellular events will facilitate optimal hit identification with high sensitivity and specificity.Herein,we propose a live-cell screening strategy using structured illumination microscopy (SIM) combined with an automated cell colocalization analysis software,CellprofilerTM,to screen and discover drugs for mitochondria and lysosomes interaction at a nanoscale resolution in living cells.This strategy quantitatively benchmarks the mitochondria-lysosome interactions such as mitochondria and lysosomes contact (MLC) and mitophagy.The automatic quantitative analysis also resolves fine changes of the mitochondria-lysosome interaction in response to genetic and pharmacological interventions.Super-resolution live-cell imaging on the basis of quantitative analysis opens up new avenues for drug screening and development by targeting dynamic organelle interactions at the nanoscale resolution,which could facilitate optimal hit identification and potentially shorten the cycle of drug discovery.

关键词： drug screening mitochondria lysosome mitophagy structured illumination microscopy