当前位置： SCI文献检索 > NATURE MEDICINE期刊下所有文献 > The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress.

The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress.

Abstract：

:Autophagy, an evolutionarily conserved process for the bulk degradation of cytoplasmic components, serves as a cell survival mechanism in starving cells. Although altered autophagy has been observed in various heart diseases, including cardiac hypertrophy and heart failure, it remains unclear whether autophagy plays a beneficial or detrimental role in the heart. Here, we report that the cardiac-specific loss of autophagy causes cardiomyopathy in mice. In adult mice, temporally controlled cardiac-specific deficiency of Atg5 (autophagy-related 5), a protein required for autophagy, led to cardiac hypertrophy, left ventricular dilatation and contractile dysfunction, accompanied by increased levels of ubiquitination. Furthermore, Atg5-deficient hearts showed disorganized sarcomere structure and mitochondrial misalignment and aggregation. On the other hand, cardiac-specific deficiency of Atg5 early in cardiogenesis showed no such cardiac phenotypes under baseline conditions, but developed cardiac dysfunction and left ventricular dilatation one week after treatment with pressure overload. These results indicate that constitutive autophagy in the heart under baseline conditions is a homeostatic mechanism for maintaining cardiomyocyte size and global cardiac structure and function, and that upregulation of autophagy in failing hearts is an adaptive response for protecting cells from hemodynamic stress.

journal_name

Nat Med

journal_title

Nature medicine

authors

Nakai A,Yamaguchi O,Takeda T,Higuchi Y,Hikoso S,Taniike M,Omiya S,Mizote I,Matsumura Y,Asahi M,Nishida K,Hori M,Mizushima N,Otsu K

doi

10.1038/nm1574

subject

Has Abstract

pub_date

2007-05-01 00:00:00

pages

619-24

issue

5

eissn

1078-8956

issn

1546-170X

pii

nm1574

journal_volume

13

pub_type

杂志文章

相关文献

NATURE MEDICINE文献大全
  • Donor CD19 CAR T cells exert potent graft-versus-lymphoma activity with diminished graft-versus-host activity.

    abstract：:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies. However, graft-versus-host disease (GVHD) and relapse after allo-HSCT remain major impediments to the success of allo-HSCT. Chimeric antigen receptors (CARs) direct tumor cell recognition of...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4258

    authors： Ghosh A,Smith M,James SE,Davila ML,Velardi E,Argyropoulos KV,Gunset G,Perna F,Kreines FM,Levy ER,Lieberman S,Jay HV,Tuckett AZ,Zakrzewski JL,Tan L,Young LF,Takvorian K,Dudakov JA,Jenq RR,Hanash AM,Motta AC,Murph

    更新日期：2017-02-01 00:00:00

  • Protective immunity from a germinal center sanctuary.

    abstract：:A new study provides mechanistic insights into how live attenuated simian immunodeficiency virus (SIV) vaccines (LAVs) can protect monkeys from infection with pathogenic SIV. The authors show that replicating LAVs stimulate a protective immune response from a safe haven in the germinal centers of lymph nodes (pages 16...

    journal_title：Nature medicine

    pub_type： 评论,杂志文章

    doi：10.1038/nm.2986

    authors： Robinson HL,Amara RR

    更新日期：2012-11-01 00:00:00

  • ORP150 protects against hypoxia/ischemia-induced neuronal death.

    abstract：:Oxygen-regulated protein 150 kD (ORP150) is a novel endoplasmic-reticulum-associated chaperone induced by hypoxia/ischemia. Although ORP150 was sparingly upregulated in neurons from human brain undergoing ischemic stress, there was robust induction in astrocytes. Cultured neurons overexpressing ORP150 were resistant t...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/85463

    authors： Tamatani M,Matsuyama T,Yamaguchi A,Mitsuda N,Tsukamoto Y,Taniguchi M,Che YH,Ozawa K,Hori O,Nishimura H,Yamashita A,Okabe M,Yanagi H,Stern DM,Ogawa S,Tohyama M

    更新日期：2001-03-01 00:00:00

  • Inducible nitric oxide synthase gene expression in the brain during systemic inflammation.

    abstract：:Inducible nitric oxide synthase (iNOS) is a transcriptionally regulated enzyme that synthesizes nitric oxide from L-arginine that has a key role in the pathophysiology of systemic inflammation and sepsis. Transgenic animals with a null mutation for the iNOS gene are resistant to hypotension and death caused by Escheri...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0596-581

    authors： Wong ML,Rettori V,al-Shekhlee A,Bongiorno PB,Canteros G,McCann SM,Gold PW,Licinio J

    更新日期：1996-05-01 00:00:00

  • Spontaneous combined hyperlipidemia, coronary heart disease and decreased survival in Dahl salt-sensitive hypertensive rats transgenic for human cholesteryl ester transfer protein.

    abstract：:The acceleration of atherosclerosis by polygenic (essential) hypertension is well-characterized in humans; however, the lack of an animal model that simulates human disease hinders the elucidation of pathogenic mechanisms. We report here a transgenic atherosclerosis-polygenic hypertension model in Dahl salt-sensitive ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/70956

    authors： Herrera VL,Makrides SC,Xie HX,Adari H,Krauss RM,Ryan US,Ruiz-Opazo N

    更新日期：1999-12-01 00:00:00

  • Persistence of HIV-1 receptor-positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition.

    abstract：:To explore the mechanism by which herpes simplex virus (HSV)-2 infection is related to HIV-1 acquisition, we conducted in situ analysis of the cellular infiltrate from sequential biopsies of HSV-2 lesions from patients on and off antiviral therapy. CD4(+) and CD8(+) T cells and a mixed population of plasmacytoid and m...

    journal_title：Nature medicine

    pub_type： 临床试验,杂志文章

    doi：10.1038/nm.2006

    authors： Zhu J,Hladik F,Woodward A,Klock A,Peng T,Johnston C,Remington M,Magaret A,Koelle DM,Wald A,Corey L

    更新日期：2009-08-01 00:00:00

  • Aura of mystery.

    abstract：:It begins as a slowly expanding spot of light or similar visual disturbance, often accompanied by phantom noises and other sensory distortions. People who experience such 'auras' know all too well that these early warning signs will culminate in a head-splitting migraine, yet scientists have little idea what causes th...

    journal_title：Nature medicine

    pub_type： 新闻

    doi：10.1038/nm0913-1083

    authors： Dolgin E

    更新日期：2013-09-01 00:00:00

  • The TAM receptor Mertk protects against neuroinvasive viral infection by maintaining blood-brain barrier integrity.

    abstract：:The TAM receptors Tyro3, Axl and Mertk are receptor tyrosine kinases that dampen host innate immune responses following engagement with their ligands Gas6 and Protein S, which recognize phosphatidylserine on apoptotic cells. In a form of apoptotic mimicry, many enveloped viruses display phosphatidylserine on the outer...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3974

    authors： Miner JJ,Daniels BP,Shrestha B,Proenca-Modena JL,Lew ED,Lazear HM,Gorman MJ,Lemke G,Klein RS,Diamond MS

    更新日期：2015-12-01 00:00:00

  • A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia.

    abstract：:Efforts to identify and annotate cancer driver genetic lesions have been focused primarily on the analysis of protein-coding genes; however, most genetic abnormalities found in human cancer are located in intergenic regions. Here we identify a new long range-acting MYC enhancer controlled by NOTCH1 that is targeted by...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3665

    authors： Herranz D,Ambesi-Impiombato A,Palomero T,Schnell SA,Belver L,Wendorff AA,Xu L,Castillo-Martin M,Llobet-Navás D,Cordon-Cardo C,Clappier E,Soulier J,Ferrando AA

    更新日期：2014-10-01 00:00:00

  • Decreased expression of AMPA receptor messenger RNA and protein in AIDS: a model for HIV-associated neurotoxicity.

    abstract：:HIV infection can cause extensive neuronal loss and clinically a severe dementia. The cause of the neurotoxicity remains unclear as neurons are not infected, but disturbance of glutamate-linked calcium entry has been implicated. In this study, we have shown a decrease in HIV-infected brain of the expression of mRNA an...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1195-1174

    authors： Everall IP,Hudson L,al-Sarraj S,Honavar M,Lantos P,Kerwin R

    更新日期：1995-11-01 00:00:00

  • Functional genomics of Neisseria meningitidis pathogenesis.

    abstract：:The pathogenic bacterium Neisseria meningitidis is an important cause of septicemia and meningitis, especially in childhood. The establishment and maintenance of bacteremic infection is a pre-requisite for all the pathological sequelae of meningococcal infection. To further understand the genetic basis of this essenti...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/81380

    authors： Sun YH,Bakshi S,Chalmers R,Tang CM

    更新日期：2000-11-01 00:00:00

  • Time to 'walk the walk' about industry ties to enhance health.

    abstract：:Overwhelming evidence that relationships between universities, physicians and the medical products industry benefit patients explains the ubiquitous calls to encourage such relationships. Yet accumulating 'conflict of interest' regulations in academic health centers, government and industry have had the opposite effec...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0411-437

    authors： Stossel TP,Stell LK

    更新日期：2011-04-01 00:00:00

  • Leukocytes mediate retinal vascular remodeling during development and vaso-obliteration in disease.

    abstract：:Retinal ischemia can cause vision-threatening pathological neovascularization. The mechanisms of retinal ischemia are not fully understood, however. Here we have shown that leukocytes prune the retinal vasculature during normal development and obliterate it in disease. Beginning at postnatal day 5 (P5) in the normal r...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm877

    authors： Ishida S,Yamashiro K,Usui T,Kaji Y,Ogura Y,Hida T,Honda Y,Oguchi Y,Adamis AP

    更新日期：2003-06-01 00:00:00

  • Glucocorticoids can promote androgen-independent growth of prostate cancer cells through a mutated androgen receptor.

    abstract：:The androgen receptor (AR) is involved in the development, growth and progression of prostate cancer (CaP). CaP often progresses from an androgen-dependent to an androgen-independent tumor, making androgen ablation therapy ineffective. However, the mechanisms for the development of androgen-independent CaP are unclear...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/76287

    authors： Zhao XY,Malloy PJ,Krishnan AV,Swami S,Navone NM,Peehl DM,Feldman D

    更新日期：2000-06-01 00:00:00

  • Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I.

    abstract：:Oxidative damage from elevated production of reactive oxygen species (ROS) contributes to ischemia-reperfusion injury in myocardial infarction and stroke. The mechanism by which the increase in ROS occurs is not known, and it is unclear how this increase can be prevented. A wide variety of nitric oxide donors and S-ni...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3212

    authors： Chouchani ET,Methner C,Nadtochiy SM,Logan A,Pell VR,Ding S,James AM,Cochemé HM,Reinhold J,Lilley KS,Partridge L,Fearnley IM,Robinson AJ,Hartley RC,Smith RA,Krieg T,Brookes PS,Murphy MP

    更新日期：2013-06-01 00:00:00

  • Simultaneous PET-MRI: a new approach for functional and morphological imaging.

    abstract：:Noninvasive imaging at the molecular level is an emerging field in biomedical research. This paper introduces a new technology synergizing two leading imaging methodologies: positron emission tomography (PET) and magnetic resonance imaging (MRI). Although the value of PET lies in its high-sensitivity tracking of bioma...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1700

    authors： Judenhofer MS,Wehrl HF,Newport DF,Catana C,Siegel SB,Becker M,Thielscher A,Kneilling M,Lichy MP,Eichner M,Klingel K,Reischl G,Widmaier S,Röcken M,Nutt RE,Machulla HJ,Uludag K,Cherry SR,Claussen CD,Pichler BJ

    更新日期：2008-04-01 00:00:00

  • Age and generational patterns of overdose death risk from opioids and other drugs.

    abstract：:The ongoing substance misuse epidemic in the United States is complex and dynamic and should be approached as such in the development and evaluation of policy1. Drug overdose deaths (largely attributable to opioid misuse) in the United States have grown exponentially for almost four decades, but the mechanisms of this...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-020-0855-y

    authors： Jalal H,Buchanich JM,Sinclair DR,Roberts MS,Burke DS

    更新日期：2020-05-01 00:00:00

  • The clock gene Per2 influences the glutamatergic system and modulates alcohol consumption.

    abstract：:Period (Per) genes are involved in regulation of the circadian clock and are thought to modulate several brain functions. We demonstrate that Per2(Brdm1) mutant mice, which have a deletion in the PAS domain of the Per2 protein, show alterations in the glutamatergic system. Lowered expression of the glutamate transport...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1163

    authors： Spanagel R,Pendyala G,Abarca C,Zghoul T,Sanchis-Segura C,Magnone MC,Lascorz J,Depner M,Holzberg D,Soyka M,Schreiber S,Matsuda F,Lathrop M,Schumann G,Albrecht U

    更新日期：2005-01-01 00:00:00

  • Mechanisms of NAFLD development and therapeutic strategies.

    abstract：:There has been a rise in the prevalence of nonalcoholic fatty liver disease (NAFLD), paralleling a worldwide increase in diabetes and metabolic syndrome. NAFLD, a continuum of liver abnormalities from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), has a variable course but can lead to cirrhosi...

    journal_title：Nature medicine

    pub_type： 杂志文章,评审

    doi：10.1038/s41591-018-0104-9

    authors： Friedman SL,Neuschwander-Tetri BA,Rinella M,Sanyal AJ

    更新日期：2018-07-01 00:00:00

  • Regulatory role for macrophage migration inhibitory factor in acute respiratory distress syndrome.

    abstract：:Migration inhibitory factor (MIF) is known to exert significant pro-inflammatory effects and has the potential to override the anti-inflammatory action of glucocorticoids. In this study we have identified significant quantities of MIF in the alveolar airspaces of patients with acute respiratory distress syndrome (ARDS...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0397-320

    authors： Donnelly SC,Haslett C,Reid PT,Grant IS,Wallace WA,Metz CN,Bruce LJ,Bucala R

    更新日期：1997-03-01 00:00:00

  • Novel role of human CD4 molecule identified in neurodegeneration.

    abstract：:The human CD4 molecule (hCD4) is expressed on T lymphocytes and macrophages and acts as a key component of the cellular receptor for HIV. At baseline, hCD4 transgenic mice expressed hCD4 on microglia, the resident mononuclear phagocytes of the brain, and showed no neuronal damage. Activation of brain microglia by peri...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0498-441

    authors： Buttini M,Westland CE,Masliah E,Yafeh AM,Wyss-Coray T,Mucke L

    更新日期：1998-04-01 00:00:00

  • Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity.

    abstract：:The ability of the human immune system to respond to vaccination declines with age. We identified an age-associated defect in T cell receptor (TCR)-induced extracellular signal-regulated kinase (ERK) phosphorylation in naive CD4(+) T cells, whereas other signals, such as ζ chain-associated protein kinase 70 (ZAP70) an...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2963

    authors： Li G,Yu M,Lee WW,Tsang M,Krishnan E,Weyand CM,Goronzy JJ

    更新日期：2012-10-01 00:00:00

  • PAI-1 mediates the antiangiogenic and profibrinolytic effects of 16K prolactin.

    abstract：:The N-terminal fragment of prolactin (16K PRL) inhibits tumor growth by impairing angiogenesis, but the underlying mechanisms are unknown. Here, we found that 16K PRL binds the fibrinolytic inhibitor plasminogen activator inhibitor-1 (PAI-1), which is known to contextually promote tumor angiogenesis and growth. Loss o...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3552

    authors： Bajou K,Herkenne S,Thijssen VL,D'Amico S,Nguyen NQ,Bouché A,Tabruyn S,Srahna M,Carabin JY,Nivelles O,Paques C,Cornelissen I,Lion M,Noel A,Gils A,Vinckier S,Declerck PJ,Griffioen AW,Dewerchin M,Martial JA,Carmeliet

    更新日期：2014-07-01 00:00:00

  • Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study.

    abstract：:Although prognostic gene expression signatures for survival in early-stage lung cancer have been proposed, for clinical application, it is critical to establish their performance across different subject populations and in different laboratories. Here we report a large, training-testing, multi-site, blinded validation...

    journal_title：Nature medicine

    pub_type： 杂志文章,多中心研究

    doi：10.1038/nm.1790

    authors： Director's Challenge Consortium for the Molecular Classification of Lung Adenocarcinoma.,Shedden K,Taylor JM,Enkemann SA,Tsao MS,Yeatman TJ,Gerald WL,Eschrich S,Jurisica I,Giordano TJ,Misek DE,Chang AC,Zhu CQ,Strumpf D,Hanash

    更新日期：2008-08-01 00:00:00

  • VEGF: a modifier of the del22q11 (DiGeorge) syndrome?

    abstract：:Hemizygous deletion of chromosome 22q11 (del22q11) causes thymic, parathyroid, craniofacial and life-threatening cardiovascular birth defects in 1 in 4,000 infants. The del22q11 syndrome is likely caused by haploinsufficiency of TBX1, but its variable expressivity indicates the involvement of additional modifiers. Her...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm819

    authors： Stalmans I,Lambrechts D,De Smet F,Jansen S,Wang J,Maity S,Kneer P,von der Ohe M,Swillen A,Maes C,Gewillig M,Molin DG,Hellings P,Boetel T,Haardt M,Compernolle V,Dewerchin M,Plaisance S,Vlietinck R,Emanuel B,Gittenb

    更新日期：2003-02-01 00:00:00

  • Combined treatment with oral metronidazole and N-acetylcysteine is effective in ethylmalonic encephalopathy.

    abstract：:Ethylmalonic encephalopathy is caused by mutations in ETHE1, a mitochondrial matrix sulfur dioxygenase, leading to failure to detoxify sulfide, a product of intestinal anaerobes and, in trace amounts, tissues. Metronidazole, a bactericide, or N-acetylcysteine, a precursor of sulfide-buffering glutathione, substantiall...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2188

    authors： Viscomi C,Burlina AB,Dweikat I,Savoiardo M,Lamperti C,Hildebrandt T,Tiranti V,Zeviani M

    更新日期：2010-08-01 00:00:00

  • Inflammasome-derived IL-1β production induces nitric oxide-mediated resistance to Leishmania.

    abstract：:Parasites of the Leishmania genus are the causative agents of leishmaniasis in humans, a disease that affects more than 12 million people worldwide. These parasites replicate intracellularly in macrophages, and the primary mechanisms underlying host resistance involve the production of nitric oxide (NO). In this study...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3221

    authors： Lima-Junior DS,Costa DL,Carregaro V,Cunha LD,Silva AL,Mineo TW,Gutierrez FR,Bellio M,Bortoluci KR,Flavell RA,Bozza MT,Silva JS,Zamboni DS

    更新日期：2013-07-01 00:00:00

  • Getting biological about the genetics of diabetes.

    abstract：:New technology has provided methods for collecting large amounts of data reflecting gene expression, metabolite and protein abundance, and post-translational modification of proteins. Integration of these various data sets enable the genetic mapping of many new phenotypes and facilitates the creation of network models...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0410-388

    authors： Newgard CB,Attie AD

    更新日期：2010-04-01 00:00:00

  • Myocardial infarction accelerates breast cancer via innate immune reprogramming.

    abstract：:Disruption of systemic homeostasis by either chronic or acute stressors, such as obesity1 or surgery2, alters cancer pathogenesis. Patients with cancer, particularly those with breast cancer, can be at increased risk of cardiovascular disease due to treatment toxicity and changes in lifestyle behaviors3-5. While eleva...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-020-0964-7

    authors： Koelwyn GJ,Newman AAC,Afonso MS,van Solingen C,Corr EM,Brown EJ,Albers KB,Yamaguchi N,Narke D,Schlegel M,Sharma M,Shanley LC,Barrett TJ,Rahman K,Mezzano V,Fisher EA,Park DS,Newman JD,Quail DF,Nelson ER,Caan BJ,J

    更新日期：2020-09-01 00:00:00

  • A GABAergic system in airway epithelium is essential for mucus overproduction in asthma.

    abstract：:Gamma-aminobutyric acid (GABA) is an important neurotransmitter that, through the subtype A GABA receptor (GABAAR), induces inhibition in the adult brain. Here we show that an excitatory, rather than inhibitory, GABAergic system exists in airway epithelial cells. Both GABAARs and the GABA synthetic enzyme glutamic aci...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1604

    authors： Xiang YY,Wang S,Liu M,Hirota JA,Li J,Ju W,Fan Y,Kelly MM,Ye B,Orser B,O'Byrne PM,Inman MD,Yang X,Lu WY

    更新日期：2007-07-01 00:00:00