Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations.

Abstract:

:Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR). A single recessive mutation, the deletion of phenylalanine 508 (deltaF508), causes severe CF and resides on 70% of mutant chromosomes. Severe CF is also caused by premature stop mutations, which are found on 5% of CF chromosomes. Here we report that two common, disease-associated stop mutations can be suppressed by treating cells with low doses of the aminoglycoside antibiotic G-418. Aminoglycoside treatment resulted in the expression of full-length CFTR and restored its cyclic AMP-activated chloride channel activity. Another aminoglycoside, gentamicin, also promoted the expression of full-length CFTR. These results suggest that treatment with aminoglycosides may provide a means of restoring CFTR function in patients with this class of mutation.

journal_name

Nat Med

journal_title

Nature medicine

authors

Howard M,Frizzell RA,Bedwell DM

doi

10.1038/nm0496-467

subject

Has Abstract

pub_date

1996-04-01 00:00:00

pages

467-9

issue

4

eissn

1078-8956

issn

1546-170X

journal_volume

2

pub_type

杂志文章
  • 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

  • α-Lipoic acid treatment prevents cystine urolithiasis in a mouse model of cystinuria.

    abstract::Cystinuria is an incompletely dominant disorder characterized by defective urinary cystine reabsorption that results in the formation of cystine-based urinary stones. Current treatment options are limited in their effectiveness at preventing stone recurrence and are often poorly tolerated. We report that the nutrition...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.4280

    authors: Zee T,Bose N,Zee J,Beck JN,Yang S,Parihar J,Yang M,Damodar S,Hall D,O'Leary MN,Ramanathan A,Gerona RR,Killilea DW,Chi T,Tischfield J,Sahota A,Kahn A,Stoller ML,Kapahi P

    更新日期:2017-03-01 00:00:00

  • Fighting tobacco dependence in Europe.

    abstract::The World Health Organization estimates that tobacco will become the largest single health problem by 2020, causing an estimated 8.4 million deaths annually. But the smoking burden will not be distributed evenly across the globe; deaths in developed nations are set to rise 50% to 2.4 million while those in Asia will s...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/83281

    authors: Raw M

    更新日期:2001-01-01 00:00:00

  • Preoperative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer: the NABUCCO trial.

    abstract::Preoperative immunotherapy with anti-PD1 plus anti-CTLA4 antibodies has shown remarkable pathological responses in melanoma1 and colorectal cancer2. In NABUCCO (ClinicalTrials.gov: NCT03387761 ), a single-arm feasibility trial, 24 patients with stage III urothelial cancer (UC) received two doses of ipilimumab and two ...

    journal_title:Nature medicine

    pub_type: 杂志文章,多中心研究

    doi:10.1038/s41591-020-1085-z

    authors: van Dijk N,Gil-Jimenez A,Silina K,Hendricksen K,Smit LA,de Feijter JM,van Montfoort ML,van Rooijen C,Peters D,Broeks A,van der Poel HG,Bruining A,Lubeck Y,Sikorska K,Boellaard TN,Kvistborg P,Vis DJ,Hooijberg E,Schumac

    更新日期:2020-12-01 00:00:00

  • Neonatal mouse immunity against group B streptococcal infection by maternal vaccination with recombinant anti-idiotypes.

    abstract::We investigated whether immunization with recombinant anti-idiotypic antibody fragments mimicking the conformation of the capsular antigen can protect against infection by group B streptococcus, an important neonatal pathogen. Single-chain fragment-variable anti-idiotypes competed with the type III carbohydrate for bi...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm0698-705

    authors: Magliani W,Polonelli L,Conti S,Salati A,Rocca PF,Cusumano V,Mancuso G,Teti G

    更新日期:1998-06-01 00:00:00

  • In vivo imaging and tracking of host-microbiota interactions via metabolic labeling of gut anaerobic bacteria.

    abstract::The intestine is densely populated by anaerobic commensal bacteria. These microorganisms shape immune system development, but understanding of host-commensal interactions is hampered by a lack of tools for studying the anaerobic intestinal environment. We applied metabolic oligosaccharide engineering and bioorthogonal...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3929

    authors: Geva-Zatorsky N,Alvarez D,Hudak JE,Reading NC,Erturk-Hasdemir D,Dasgupta S,von Andrian UH,Kasper DL

    更新日期:2015-09-01 00:00:00

  • Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo.

    abstract::Neutrophil extracellular traps (NETs) are released as neutrophils die in vitro in a process requiring hours, leaving a temporal gap that invasive microbes may exploit. Neutrophils capable of migration and phagocytosis while undergoing NETosis have not been documented. During Gram-positive skin infections, we directly ...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.2847

    authors: Yipp BG,Petri B,Salina D,Jenne CN,Scott BN,Zbytnuik LD,Pittman K,Asaduzzaman M,Wu K,Meijndert HC,Malawista SE,de Boisfleury Chevance A,Zhang K,Conly J,Kubes P

    更新日期:2012-09-01 00:00:00

  • Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection.

    abstract::Viral replication and microbial translocation from the gut to the blood during HIV infection lead to hyperimmune activation, which contributes to the decline in CD4+ T cell numbers during HIV infection. Programmed death-1 (PD-1) and interleukin-10 (IL-10) are both upregulated during HIV infection. Blocking interaction...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.2106

    authors: Said EA,Dupuy FP,Trautmann L,Zhang Y,Shi Y,El-Far M,Hill BJ,Noto A,Ancuta P,Peretz Y,Fonseca SG,Van Grevenynghe J,Boulassel MR,Bruneau J,Shoukry NH,Routy JP,Douek DC,Haddad EK,Sekaly RP

    更新日期:2010-04-01 00:00:00

  • CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma.

    abstract::Although subtypes of pancreatic ductal adenocarcinoma (PDAC) have been described, this malignancy is clinically still treated as a single disease. Here we present patient-derived models representing the full spectrum of previously identified quasi-mesenchymal (QM-PDA), classical and exocrine-like PDAC subtypes, and id...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.4038

    authors: Noll EM,Eisen C,Stenzinger A,Espinet E,Muckenhuber A,Klein C,Vogel V,Klaus B,Nadler W,Rösli C,Lutz C,Kulke M,Engelhardt J,Zickgraf FM,Espinosa O,Schlesner M,Jiang X,Kopp-Schneider A,Neuhaus P,Bahra M,Sinn BV,Eil

    更新日期:2016-03-01 00:00:00

  • Vitamin E decreases bone mass by stimulating osteoclast fusion.

    abstract::Bone homeostasis is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption. Osteoclasts are multinucleated cells that are formed by mononuclear preosteoclast fusion. Fat-soluble vitamins such as vitamin D are pivotal in maintaining skeletal integrity. However, the role of vitami...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.2659

    authors: Fujita K,Iwasaki M,Ochi H,Fukuda T,Ma C,Miyamoto T,Takitani K,Negishi-Koga T,Sunamura S,Kodama T,Takayanagi H,Tamai H,Kato S,Arai H,Shinomiya K,Itoh H,Okawa A,Takeda S

    更新日期:2012-03-04 00:00:00

  • Mutations in G protein β subunits promote transformation and kinase inhibitor resistance.

    abstract::Activating mutations in genes encoding G protein α (Gα) subunits occur in 4-5% of all human cancers, but oncogenic alterations in Gβ subunits have not been defined. Here we demonstrate that recurrent mutations in the Gβ proteins GNB1 and GNB2 confer cytokine-independent growth and activate canonical G protein signalin...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3751

    authors: Yoda A,Adelmant G,Tamburini J,Chapuy B,Shindoh N,Yoda Y,Weigert O,Kopp N,Wu SC,Kim SS,Liu H,Tivey T,Christie AL,Elpek KG,Card J,Gritsman K,Gotlib J,Deininger MW,Makishima H,Turley SJ,Javidi-Sharifi N,Maciejewski

    更新日期:2015-01-01 00:00:00

  • Clinical microfluidics for neutrophil genomics and proteomics.

    abstract::Neutrophils have key roles in modulating the immune response. We present a robust methodology for rapidly isolating neutrophils directly from whole blood with 'on-chip' processing for mRNA and protein isolation for genomics and proteomics. We validate this device with an ex vivo stimulation experiment and by compariso...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.2205

    authors: Kotz KT,Xiao W,Miller-Graziano C,Qian WJ,Russom A,Warner EA,Moldawer LL,De A,Bankey PE,Petritis BO,Camp DG 2nd,Rosenbach AE,Goverman J,Fagan SP,Brownstein BH,Irimia D,Xu W,Wilhelmy J,Mindrinos MN,Smith RD,Davis RW

    更新日期:2010-09-01 00:00:00

  • gammadelta T cells provide a breath of fresh air for asthma research.

    abstract::gammadelta T cells downregulate airways responsiveness to allergen challenge, possibly by controlling the 'repair' response of the airway epithelium to alphabeta T cell-mediated damage (pages 1150-1156). ...

    journal_title:Nature medicine

    pub_type: 评论,新闻

    doi:10.1038/13447

    authors: Holt PG,Sly PD

    更新日期:1999-10-01 00:00:00

  • Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer.

    abstract::Expression of the oncogenic transcription factor MYC is disproportionately elevated in triple-negative breast cancer (TNBC), as compared to estrogen receptor-, progesterone receptor- or human epidermal growth factor 2 receptor-positive (RP) breast cancer. We and others have shown that MYC alters metabolism during tumo...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.4055

    authors: Camarda R,Zhou AY,Kohnz RA,Balakrishnan S,Mahieu C,Anderton B,Eyob H,Kajimura S,Tward A,Krings G,Nomura DK,Goga A

    更新日期:2016-04-01 00:00:00

  • Adhesion of Plasmodium falciparum-infected erythrocytes to hyaluronic acid in placental malaria.

    abstract::Infection with Plasmodium falciparum during pregnancy leads to the accumulation of parasite-infected erythrocytes in the placenta, and is associated with excess perinatal mortality, premature delivery and intrauterine growth retardation in the infant, as well as increased maternal mortality and morbidity. P. falciparu...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/71582

    authors: Beeson JG,Rogerson SJ,Cooke BM,Reeder JC,Chai W,Lawson AM,Molyneux ME,Brown GV

    更新日期:2000-01-01 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

  • Modulation of splicing catalysis for therapeutic targeting of leukemia with mutations in genes encoding spliceosomal proteins.

    abstract::Mutations in genes encoding splicing factors (which we refer to as spliceosomal genes) are commonly found in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). These mutations recurrently affect specific amino acid residues, leading to perturbed normal splice site and exon recognition. Spl...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.4097

    authors: Lee SC,Dvinge H,Kim E,Cho H,Micol JB,Chung YR,Durham BH,Yoshimi A,Kim YJ,Thomas M,Lobry C,Chen CW,Pastore A,Taylor J,Wang X,Krivtsov A,Armstrong SA,Palacino J,Buonamici S,Smith PG,Bradley RK,Abdel-Wahab O

    更新日期:2016-06-01 00:00:00

  • Wearable sensor data and self-reported symptoms for COVID-19 detection.

    abstract::Traditional screening for COVID-19 typically includes survey questions about symptoms and travel history, as well as temperature measurements. Here, we explore whether personal sensor data collected over time may help identify subtle changes indicating an infection, such as in patients with COVID-19. We have developed...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-020-1123-x

    authors: Quer G,Radin JM,Gadaleta M,Baca-Motes K,Ariniello L,Ramos E,Kheterpal V,Topol EJ,Steinhubl SR

    更新日期:2021-01-01 00:00:00

  • Natural regulatory T cells control the development of atherosclerosis in mice.

    abstract::Atherosclerosis is an immunoinflammatory disease elicited by accumulation of lipids in the artery wall and leads to myocardial infarction and stroke. Here, we show that naturally arising CD4(+)CD25(+) regulatory T cells, which actively maintain immunological tolerance to self and nonself antigens, are powerful inhibit...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1343

    authors: Ait-Oufella H,Salomon BL,Potteaux S,Robertson AK,Gourdy P,Zoll J,Merval R,Esposito B,Cohen JL,Fisson S,Flavell RA,Hansson GK,Klatzmann D,Tedgui A,Mallat Z

    更新日期:2006-02-01 00:00:00

  • A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is protective in heart failure.

    abstract::Beta-adrenergic receptor (betaAR) blockade is a standard therapy for cardiac failure and ischemia. G protein-coupled receptor kinases (GRKs) desensitize betaARs, suggesting that genetic GRK variants might modify outcomes in these syndromes. Re-sequencing of GRK2 and GRK5 revealed a nonsynonymous polymorphism of GRK5, ...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1750

    authors: Liggett SB,Cresci S,Kelly RJ,Syed FM,Matkovich SJ,Hahn HS,Diwan A,Martini JS,Sparks L,Parekh RR,Spertus JA,Koch WJ,Kardia SL,Dorn GW 2nd

    更新日期:2008-05-01 00:00:00

  • Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma.

    abstract::Whereas uncoupling protein 1 (UCP-1) is clearly involved in thermogenesis, the role of UCP-2 is less clear. Using hybridization, cloning techniques and cDNA array analysis to identify inducible neuroprotective genes, we found that neuronal survival correlates with increased expression of Ucp2. In mice overexpressing h...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm903

    authors: Mattiasson G,Shamloo M,Gido G,Mathi K,Tomasevic G,Yi S,Warden CH,Castilho RF,Melcher T,Gonzalez-Zulueta M,Nikolich K,Wieloch T

    更新日期:2003-08-01 00:00:00

  • The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux.

    abstract::Cytochrome P450 3A4 is an important mediator of drug catabolism that can be regulated by the steroid and xenobiotic receptor (SXR). We show here that SXR also regulates drug efflux by activating expression of the gene MDR1, which encodes the protein P-glycoprotein (ABCB1). Paclitaxel (Taxol), a commonly used chemother...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/87912

    authors: Synold TW,Dussault I,Forman BM

    更新日期:2001-05-01 00:00:00

  • ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents.

    abstract::The 55-kilodalton (kDa) protein from the E1B-region of adenovirus binds to and inactivates the p53 gene, which is mutated in half of human cancers. We have previously shown that the replication and cytopathogenicity of an E1B, 55-kDa gene-attenuated adenovirus, ONYX-015, is blocked by functional p53 in RKO and U20S ca...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm0697-639

    authors: Heise C,Sampson-Johannes A,Williams A,McCormick F,Von Hoff DD,Kirn DH

    更新日期:1997-06-01 00:00:00

  • Inducer-stimulated Fas targets activated endothelium for destruction by anti-angiogenic thrombospondin-1 and pigment epithelium-derived factor.

    abstract::Natural inhibitors of angiogenesis are able to block pathological neovascularization without harming the preexisting vasculature. Here we show that two such inhibitors, thrombospondin-1 and pigment epithelium-derived factor, derive specificity for remodeling vessels from their dependence on Fas/Fas ligand (FasL)-media...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm0402-349

    authors: Volpert OV,Zaichuk T,Zhou W,Reiher F,Ferguson TA,Stuart PM,Amin M,Bouck NP

    更新日期:2002-04-01 00:00:00

  • A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome.

    abstract::The identification of the genes associated with chromosomal translocation breakpoints has fundamentally changed understanding of the molecular basis of hematological malignancies. By contrast, the study of chromosomal deletions has been hampered by the large number of genes deleted and the complexity of their analysis...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.2063

    authors: Barlow JL,Drynan LF,Hewett DR,Holmes LR,Lorenzo-Abalde S,Lane AL,Jolin HE,Pannell R,Middleton AJ,Wong SH,Warren AJ,Wainscoat JS,Boultwood J,McKenzie AN

    更新日期:2010-01-01 00:00:00

  • Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses.

    abstract::Mesenchymal tumor subpopulations secrete pro-tumorigenic cytokines and promote treatment resistance1-4. This phenomenon has been implicated in chemorefractory small cell lung cancer and resistance to targeted therapies5-8, but remains incompletely defined. Here, we identify a subclass of endogenous retroviruses (ERVs)...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-018-0116-5

    authors: Cañadas I,Thummalapalli R,Kim JW,Kitajima S,Jenkins RW,Christensen CL,Campisi M,Kuang Y,Zhang Y,Gjini E,Zhang G,Tian T,Sen DR,Miao D,Imamura Y,Thai T,Piel B,Terai H,Aref AR,Hagan T,Koyama S,Watanabe M,Baba H,

    更新日期:2018-08-01 00:00:00

  • The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development.

    abstract::The gene encoding the lysine-specific histone methyltransferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma and diffuse large B cell lymphoma; however, the biological consequences of KMT2D mutations on lymphoma development are not known. Here we show that KMT2D functions as a b...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3943

    authors: Ortega-Molina A,Boss IW,Canela A,Pan H,Jiang Y,Zhao C,Jiang M,Hu D,Agirre X,Niesvizky I,Lee JE,Chen HT,Ennishi D,Scott DW,Mottok A,Hother C,Liu S,Cao XJ,Tam W,Shaknovich R,Garcia BA,Gascoyne RD,Ge K,Shilatif

    更新日期:2015-10-01 00:00:00

  • PAF-mediated pulmonary edema: a new role for acid sphingomyelinase and ceramide.

    abstract::Platelet-activating factor (PAF) induces pulmonary edema and has a key role in acute lung injury (ALI). Here we show that PAF induces pulmonary edema through two mechanisms: acid sphingomyelinase (ASM)-dependent production of ceramide, and activation of the cyclooxygenase pathway. Agents that interfere with PAF-induce...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm977

    authors: Göggel R,Winoto-Morbach S,Vielhaber G,Imai Y,Lindner K,Brade L,Brade H,Ehlers S,Slutsky AS,Schütze S,Gulbins E,Uhlig S

    更新日期:2004-02-01 00:00:00

  • Protectin DX alleviates insulin resistance by activating a myokine-liver glucoregulatory axis.

    abstract::We previously demonstrated that low biosynthesis of ω-3 fatty acid-derived proresolution mediators, termed protectins, is associated with an impaired global resolution capacity, inflammation and insulin resistance in obese high-fat diet-fed mice. These findings prompted a more direct study of the therapeutic potential...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3549

    authors: White PJ,St-Pierre P,Charbonneau A,Mitchell PL,St-Amand E,Marcotte B,Marette A

    更新日期:2014-06-01 00:00:00

  • Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants.

    abstract::Defects in major histocompatibility complex (MHC) class I-restricted antigen presentation are frequently observed in human cancers and result in escape of tumors from cytotoxic T lymphocyte (CTL) immune surveillance in mice. Here, we show the existence of a unique category of CTLs that can prevent this escape. The CTL...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1381

    authors: van Hall T,Wolpert EZ,van Veelen P,Laban S,van der Veer M,Roseboom M,Bres S,Grufman P,de Ru A,Meiring H,de Jong A,Franken K,Teixeira A,Valentijn R,Drijfhout JW,Koning F,Camps M,Ossendorp F,Kärre K,Ljunggren HG,Mel

    更新日期:2006-04-01 00:00:00