Cell Stress最新文献_第8页

Exploiting the circuit breaker cancer evolution model in human clear cell renal cell carcinoma. 人透明细胞肾细胞癌断路器癌进化模型的建立。

IF 6.4

Cell Stress Pub Date : 2020-06-25 DOI: 10.15698/cst2020.08.227

James J Hsieh, Emily H Cheng

{"title":"Exploiting the circuit breaker cancer evolution model in human clear cell renal cell carcinoma.","authors":"James J Hsieh, Emily H Cheng","doi":"10.15698/cst2020.08.227","DOIUrl":"10.15698/cst2020.08.227","url":null,"abstract":"The incessant interactions between susceptible humans and their respective macro/microenvironments registered throughout their lifetime result in the ultimate manifestation of individual cancers. With the average lifespan exceeding 50 years of age in humans since the beginning of 20th century, aging - the \"time\" factor - has played an ever-increasing role alongside host and environmental factors in cancer incidences. Cancer is a genetic/epigenetic disease due to gain-of-function mutations in cancer-causing genes (oncogene; OG) and/or loss-of-function mutations in tumor-suppressing genes (tumor suppressor genes; TSG). In addition to their integral relationship with cancer, a timely deployment of specific OG and/or TSG is in fact needed for higher organisms like human to cope with respective physiological and pathological conditions. Over the past decade, extensive human kidney cancer genomics have been performed and novel mouse models recapitulating human kidney cancer pathobiology have been generated. With new genomic, genetic, mechanistic, clinical and therapeutic insights accumulated from studying clear cell renal cell carcinoma (ccRCC)-the most common type of kidney cancer, we conceived a cancer evolution model built upon the OG-TSG signaling pair analogous to the electrical circuit breaker (CB) that permits necessary signaling output and at the same time prevent detrimental signaling overdrive. Hence, this viewpoint aims at providing a step-by-step mechanistic explanation/illustration concerning how inherent OG-TSG CBs intricately operate in concert for the organism's wellbeing; and how somatic mutations, the essential component for genetic adaptability, inadvertently triggers a sequential outage of specific sets of CBs that normally function to maintain and protect and individual tissue homeostasis.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"4 8","pages":"191-198"},"PeriodicalIF":6.4,"publicationDate":"2020-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38228742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

High mitochondrial calcium levels precede neuronal death in vivo in Alzheimer's disease. 阿尔茨海默病患者体内高线粒体钙水平先于神经元死亡。

IF 6.4

Cell Stress Pub Date : 2020-06-18 DOI: 10.15698/cst2020.07.226

Maria Calvo-Rodriguez, Brian J Bacskai

{"title":"High mitochondrial calcium levels precede neuronal death in vivo in Alzheimer's disease.","authors":"Maria Calvo-Rodriguez, Brian J Bacskai","doi":"10.15698/cst2020.07.226","DOIUrl":"https://doi.org/10.15698/cst2020.07.226","url":null,"abstract":"Alzheimer's disease (AD), the most common cause of dementia, affects millions of people worldwide. Suggested mechanisms of neurotoxicity in AD include impaired calcium (Ca2+) homeostasis and mitochondrial dysfunction, both contributing to neuronal damage. Little was known about the exact mitochondrial Ca2+ homeostasis in the living brain, particularly in AD. Only now, with the development of intravital imaging techniques and transgenic mouse models of the disease, we are able to directly observe Ca2+ levels in specific regions or particular subcellular compartments of cells, such as mitochondria. Using multiphoton microscopy, a Ca2+ reporter targeted to mitochondria and a mouse model of cerebral β amyloidosis (APP/PS1), our recent study (Nat Comms 2020, 11:2146) found elevated mitochondrial Ca2+ concentration in the transgenic mouse after plaque deposition, and after topical application of natural soluble amyloid beta (Aβ) oligomers to the healthy mouse brain at concentrations similar to those found in the human brain. Elevated Ca2+ in mitochondria preceded neuronal death and could be targeted for neuroprotective therapies in AD. Here, we describe our main findings and pose new questions for future studies aimed at better understanding mitochondrial Ca2+ dyshomeostasis in AD.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"4 7","pages":"187-190"},"PeriodicalIF":6.4,"publicationDate":"2020-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38144967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

The role of lipids in autophagy and its implication in neurodegeneration. 脂质在自噬中的作用及其在神经变性中的意义。

IF 6.4

Cell Stress Pub Date : 2020-05-19 DOI: 10.15698/cst2020.07.225

Sergio Hernandez-Diaz, Sandra-Fausia Soukup

{"title":"The role of lipids in autophagy and its implication in neurodegeneration.","authors":"Sergio Hernandez-Diaz, Sandra-Fausia Soukup","doi":"10.15698/cst2020.07.225","DOIUrl":"https://doi.org/10.15698/cst2020.07.225","url":null,"abstract":"Neurodegenerative diseases are, at present, major socio-economic burdens without effective treatments and their increasing prevalence means that these diseases will be a challenge for future generations. Neurodegenerative diseases may differ in etiology and pathology but are often caused by the accumulation of dysfunctional and aggregation-prone proteins. Autophagy, a conserved cellular mechanism, deals with cellular stress and waste product build-up and has been shown to reduce the accumulation of dysfunctional proteins in animal models of neurodegenerative diseases. Historically, progress in understanding the precise function of lipids has traditionally been far behind other biological molecules (like proteins) but emerging works demonstrate the importance of lipids in the autophagy pathway and how the disturbance of lipid metabolism is connected to neurodegeneration. Here we review how altered autophagy and the disturbance of lipid metabolism, particularly of phosphoinositols and sphingolipids, feature in neurodegenerative diseases and address work from the field that suggests that these potentially offer an opportunity of therapeutic intervention.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"4 7","pages":"167-186"},"PeriodicalIF":6.4,"publicationDate":"2020-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38144969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 16

Immune system activation by natural products and complex fractions: a network pharmacology approach in cancer treatment. 天然产物和复杂组分激活免疫系统:癌症治疗中的网络药理学方法。

IF 6.4

Cell Stress Pub Date : 2020-05-18 DOI: 10.15698/cst2020.07.224

Alejandra Gomez-Cadena, Alfonso Barreto, Susana Fioretino, Camilla Jandus

引用次数: 10

Mitochondria, mitophagy, and metabolic disease: towards assembling the puzzle. 线粒体、线粒体自噬和代谢性疾病:走向拼图。

IF 6.4

Cell Stress Pub Date : 2020-05-14 DOI: 10.15698/cst2020.06.222

Zhiyong Chen, Marine Berquez, Alessandro Luciani

{"title":"Mitochondria, mitophagy, and metabolic disease: towards assembling the puzzle.","authors":"Zhiyong Chen, Marine Berquez, Alessandro Luciani","doi":"10.15698/cst2020.06.222","DOIUrl":"https://doi.org/10.15698/cst2020.06.222","url":null,"abstract":"Dysregulation of the mitochondrial network in terminally differentiated cells contributes to a broad spectrum of disorders. Methylmalonic acidemia (MMA) is an autosomal recessive inborn error of intermediary metabolism caused by the deficiency of methylmalonyl-CoA mutase (MMUT) - a mitochondrial enzyme that mediates the degradation of certain amino acids and lipids. The loss of MMUT activity triggers an accumulation of toxic endogenous metabolites causing severe organ dysfunctions and life-threatening complications. How MMUT deficiency instigates mitochondrial distress and tissue damage remains poorly understood. Using cell and animal-based models, we recently discovered that MMUT deficiency disables the PINK1-induced translocation of PRKN/Parkin to MMA-damaged mitochondria, impeding their delivery and subsequent dismantling by macroautophagy/autophagy-lysosome degradation systems (Luciani et al. Nat Commun. 11(1):970). This promotes an accumulation of damaged and/or dysfunctional mitochondria that spark epithelial distress and tissue damage. Using a systems biology approach based on drug-disease network perturbation modeling, we predicted targetable pathways, whose modulation repairs mitochondrial dysfunctions in patient-derived kidney cells and ameliorates disease-relevant phenotypes in mmut-deficient zebrafish. These results unveil a link between primary MMUT deficiency, defective mitophagy, and cell distress, offering promising therapeutic avenues for MMA and other mitochondria-related diseases.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"4 6","pages":"147-150"},"PeriodicalIF":6.4,"publicationDate":"2020-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38055233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

HIF1α or mitophagy: which drives cardiomyocyte differentiation? HIF1α和有丝分裂：哪个驱动心肌细胞分化？

IF 6.4

Cell Stress Pub Date : 2020-05-11 DOI: 10.15698/cst2020.05.219

Beatriz Villarejo-Zori, Juan Ignacio Jiménez-Loygorri, Patricia Boya

引用次数: 0

Mitochondria in cancer. 癌症中的线粒体。

IF 6.4

Cell Stress Pub Date : 2020-05-11 DOI: 10.15698/cst2020.06.221

Debora Grasso, Luca X Zampieri, Tânia Capelôa, Justine A Van de Velde, Pierre Sonveaux

引用次数: 94

Copper - a novel stimulator of autophagy. 铜——一种新的自噬刺激剂。

IF 6.4

Cell Stress Pub Date : 2020-04-24 DOI: 10.15698/cst2020.05.218

Hans Zischka, Guido Kroemer

引用次数: 17

Towards understanding the role of Receptor Expression Enhancing Protein 5 (REEP5) in cardiac muscle and beyond. 了解受体表达增强蛋白5 (REEP5)在心肌及其他部位的作用。

IF 6.4

Cell Stress Pub Date : 2020-04-15 DOI: 10.15698/cst2020.06.223

Shin-Haw Lee, Sina Hadipour-Lakmehsari, Anthony O Gramolini

{"title":"Towards understanding the role of Receptor Expression Enhancing Protein 5 (REEP5) in cardiac muscle and beyond.","authors":"Shin-Haw Lee, Sina Hadipour-Lakmehsari, Anthony O Gramolini","doi":"10.15698/cst2020.06.223","DOIUrl":"https://doi.org/10.15698/cst2020.06.223","url":null,"abstract":"The sarco-endoplasmic reticulum (SR/ER) is the largest membrane-bound organelle in eukaryotic cells and plays important roles in essential cellular processes, and in development and progression of many cardiac diseases. However, many aspects of its structural organization remain largely unknown, particularly in cells with a highly differentiated SR/ER network. In a recently published study led by Lee et al. (Nat Commun 11(1):965), we reported a cardiac enriched SR/ER membrane protein REEP5 that is centrally involved in regulating SR/ER organization and cellular stress responses in cardiac myocytes. In vitro REEP5 depletion in mouse cardiac myocytes resulted in SR/ER membrane destabilization and luminal vacuolization along with decreased myocyte contractility and disrupted Ca2+ cycling. Further, in vivo CRISPR/Cas9-mediated REEP5 loss-of-function zebrafish mutants showed sensitized cardiac dysfunction to heart failure induction upon short-term verapamil treatment. Additionally, in vivo adeno-associated viral (AAV9)-induced REEP5 depletion in the mouse demonstrated cardiac dysfunction with dilated cardiac chambers, increased cardiac fibrosis, and reduced ejection fraction. These results demonstrate the critical role of REEP5 in SR/ER organization and function.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"4 6","pages":"151-153"},"PeriodicalIF":6.4,"publicationDate":"2020-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38055234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Role of RNA Binding Proteins with prion-like domains in muscle and neuromuscular diseases. 带有朊病毒样结构域的RNA结合蛋白在肌肉和神经肌肉疾病中的作用。

IF 6.4

Cell Stress Pub Date : 2020-03-10 DOI: 10.15698/cst2020.04.217

Gina Picchiarelli, Luc Dupuis

引用次数: 33