CoChat
Sign Up
Cited by 256Muscle Physiology and DisordersImmune Response and InflammationNutrition and Health in Aging

Toll‐like receptor 4 mediates lipopolysaccharide‐induced muscle catabolism via coordinate activation of ubiquitin‐proteasome and autophagy‐lysosome pathways

Open access
Doyle, Alexander, Zhang, Guohua, Fattah, Elmoataz A. Abdel, Eissa, N. Tony, Li, Yi‐Ping·2011·The FASEB Journal
DOI 10.1096/fj.10-164152PMC PMC3005430
Open this paper in CoChat — free account

Abstract

Cachectic muscle wasting is a frequent complication of many inflammatory conditions, due primarily to excessive muscle catabolism. However, the pathogenesis and intervention strategies against it remain to be established. Here, we tested the hypothesis that Toll‐like receptor 4 (TLR4) is a master regulator of inflammatory muscle catabolism. We demonstrate that TLR4 activation by lipopolysac‐charide (LPS) induces C2C12 myotube atrophy via up‐regulating autophagosome formation and the expression of ubiquitin ligase atrogin‐1/MAFbx and MuRF1. TLR4‐mediated activation of p38 MAPK is necessary and sufficient for the up‐regulation of atrogin1/MAFbx and autophagosomes, resulting in myotube atrophy. Similarly, LPS up‐regulates muscle autophagosome formation and ubiquitin ligase expression in mice. Importantly, autophagy inhibitor 3‐methyladenine completely abolishes LPS‐induced muscle proteolysis, while proteasome inhibitor lacta‐cystin partially blocks it. Furthermore, TLR4 knockout or p38 MAPK inhibition abolishes LPS‐induced muscle proteolysis. Thus, TLR4 mediates LPS‐induced muscle catabolism via coordinate activation of the ubiq‐uitin‐proteasome and the autophagy‐lysosomal pathways.—Doyle, A., Zhang, G., Abdel Fattah, E. A., Eissa, N. T., Li, Y.‐P. Toll‐like receptor 4 mediates lipopolysac‐charide‐induced muscle catabolism via coordinate activation of ubiquitin‐proteasome and autophagy‐lysosome pathways. FASEB J. 25, 99–110 (2011). www.fasebj.org

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1096/fj.10-164152

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Two studies outside the COPD context point towards a prominent role of the TLR-4 pathway in muscle wasting, via activation of the p38-MAPK atrophy pathway.

    “Two studies outside the COPD context also point towards a prominent role of the Toll-like receptor (TLR)-4 pathway in muscle wasting, via the activation of the p38-MAPK atrophy pathway [63,64].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [63]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 57 · Cited by 256

Research works printed but not linked: 52

  1. [1]1. Evans W. J., Morley J. E., Argiles J., Bales C., Baracos V., Guttridge D., Jatoi A., Kalantar-Zadeh K., Lochs H., Mantovani G., Marks D., Mitch W. E., Muscaritoli M., Najand A., Ponikowski P., Rossi Fanelli F., Schambelan M., Schols A., Schuster M., Thomas D., Wolfe R., Anker S. D. (2008) Cachexia: a new definition. Clin. Nutr. 27, 793–799 [DOI] [PubMed] [Google Scholar]
  2. [2]2. Solomon V., Goldberg A. L. (1996) Importance of the ATP-ubiquitin-proteasome pathway in the degradation of soluble and myofibrillar proteins in rabbit muscle extracts. J. Biol. Chem. 271, 26690–26697 [DOI] [PubMed] [Google Scholar]
  3. [3]3. Bechet D., Tassa A., Taillandier D., Combaret L., Attaix D. (2005) Lysosomal proteolysis in skeletal muscle. Int. J. Biochem. Cell Biol. 37, 2098–2114 [DOI] [PubMed] [Google Scholar]
  4. [4]4. Kirkin V., McEwan D. G., Novak I., Dikic I. (2009) A role for ubiquitin in selective autophagy. Mol. Cell 34, 259–269 [DOI] [PubMed] [Google Scholar]
  5. [5]5. Lecker S. H., Goldberg A. L., Mitch W. E. (2006) Protein degradation by the ubiquitin-proteasome pathway in normal and disease states. J. Am. Soc. Nephrol. 17, 1807–1819 [DOI] [PubMed] [Google Scholar]
  6. [6]6. Bodine S. C., Latres E., Baumhueter S., Lai V. K., Nunez L., Clarke B. A., Poueymirou W. T., Panaro F. J., Na E., Dharmarajan K., Pan Z. Q., Valenzuela D. M., DeChiara T. M., Stitt T. N., Yancopoulos G. D., Glass D. J. (2001) Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294, 1704–1708 [DOI] [PubMed] [Google Scholar]
  7. [7]7. Gomes M. D., Lecker S. H., Jagoe R. T., Navon A., Goldberg A. L. (2001) Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc. Natl. Acad. Sci. U. S. A. 98, 14440–14445 [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. [9]9. Stitt T. N., Drujan D., Clarke B. A., Panaro F., Timofeyva Y., Kline W. O., Gonzalez M., Yancopoulos G. D., Glass D. J. (2004) The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol. Cell 14, 395–403 [DOI] [PubMed] [Google Scholar]
  9. [11]11. Argiles J. M., Alvarez B., Carbo N., Busquets S., Van Royen M., Lopez-Soriano F. J. (2000) The divergent effects of tumour necrosis factor-alpha on skeletal muscle: implications in wasting. Eur. Cytokine Netw. 11, 552–559 [PubMed] [Google Scholar]
  10. [12]12. Moylan J. S., Smith J. D., Chambers M. A., McLoughlin T. J., Reid M. B. (2008) TNF induction of atrogin-1/MAFbx mRNA depends on Foxo4 expression but not AKT-Foxo1/3 signaling. Am. J. Physiol. Cell Physiol. 295, C986–C993 [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. [13]13. Li Y. P., Chen Y., John J., Moylan J., Jin B., Mann D. L., Reid M. B. (2005) TNF-alpha acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle. FASEB J. 19, 362–370 [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. [15]15. Goldberg R. M., Loprinzi C. L., Mailliard J. A., O'Fallon J. R., Krook J. E., Ghosh C., Hestorff R. D., Chong S. F., Reuter N. F., Shanahan T. G. (1995) Pentoxifylline for treatment of cancer anorexia and cachexia? A randomized, double-blind, placebo-controlled trial. J. Clin. Oncol. 13, 2856–2859 [DOI] [PubMed] [Google Scholar]
  13. [16]16. Liu K. H., Liao L. M., Ro L. S., Wu Y. L., Yeh T. S. (2008) Thalidomide attenuates tumor growth and preserves fast-twitch skeletal muscle fibers in cholangiocarcinoma rats. Surgery 143, 375–383 [DOI] [PubMed] [Google Scholar]
  14. [17]17. Li W., Moylan J. S., Chambers M. A., Smith J., Reid M. B. (2009) Interleukin-1 stimulates catabolism in C2C12 myotubes. Am. J. Physiol. Cell Physiol. 297, C706–C714 [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. [18]18. Baltgalvis K. A., Berger F. G., Pena M. M., Davis J. M., White J. P., Carson J. A. (2009) Muscle wasting and interleukin-6-induced atrogin-I expression in the cachectic Apc (Min/+) mouse. Pflügers Arch. 457, 989–1001 [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. [19]19. Zhao J., Brault J. J., Schild A., Cao P., Sandri M., Schiaffino S., Lecker S. H., Goldberg A. L. (2007) FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell. Metab. 6, 472–483 [DOI] [PubMed] [Google Scholar]
  17. [20]20. Mammucari C., Milan G., Romanello V., Masiero E., Rudolf R., Del Piccolo P., Burden S. J., Di Lisi R., Sandri C., Zhao J., Goldberg A. L., Schiaffino S., Sandri M. (2007) FoxO3 controls autophagy in skeletal muscle in vivo. Cell. Metab. 6, 458–471 [DOI] [PubMed] [Google Scholar]
  18. [21]21. Zhao J., Brault J. J., Schild A., Goldberg A. L. (2008) Coordinate activation of autophagy and the proteasome pathway by FoxO transcription factor. Autophagy 4, 378–380 [DOI] [PubMed] [Google Scholar]
  19. [22]22. Rosenblatt S., Clowes G. H., Jr., George B. C., Hirsch E., Lindberg B. (1983) Exchange of amino acids by muscle and liver in sepsis. Arch. Surg. 118, 167–175 [DOI] [PubMed] [Google Scholar]
  20. [23]23. Hasselgren P. O., Talamini M., James J. H., Fischer J. E. (1986) Protein metabolism in different types of skeletal muscle during early and late sepsis in rats. Arch. Surg. 121, 918–923 [DOI] [PubMed] [Google Scholar]
  21. [24]24. Hasselgren P. O., James J. H., Benson D. W., Hall-Angeras M., Angeras U., Hiyama D. T., Li S., Fischer J. E. (1989) Total and myofibrillar protein breakdown in different types of rat skeletal muscle: effects of sepsis and regulation by insulin. Metabolism 38, 634–640 [DOI] [PubMed] [Google Scholar]
  22. [25]25. Tiao G., Fagan J. M., Samuels N., James J. H., Hudson K., Lieberman M., Fischer J. E., Hasselgren P. O. (1994) Sepsis stimulates nonlysosomal, energy-dependent proteolysis and increases ubiquitin mRNA levels in rat skeletal muscle. J. Clin. Invest. 94, 2255–2264 [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. [26]26. Tiao G., Hobler S., Wang J. J., Meyer T. A., Luchette F. A., Fischer J. E., Hasselgren P. O. (1997) Sepsis is associated with increased mRNAs of the ubiquitin-proteasome proteolytic pathway in human skeletal muscle. J. Clin. Invest. 99, 163–168 [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. [27]27. Wray C. J., Mammen J. M., Hershko D. D., Hasselgren P. O. (2003) Sepsis upregulates the gene expression of multiple ubiquitin ligases in skeletal muscle. Int. J. Biochem. Cell Biol. 35, 698–705 [DOI] [PubMed] [Google Scholar]
  25. [28]28. Dehoux M. J., van Beneden R. P., Fernandez-Celemin L., Lause P. L., Thissen J. P. (2003) Induction of MafBx and Murf ubiquitin ligase mRNAs in rat skeletal muscle after LPS injection. FEBS Lett. 544, 214–217 [DOI] [PubMed] [Google Scholar]
  26. [29]29. Vary T. C. (1998) Regulation of skeletal muscle protein turnover during sepsis. Curr. Opin. Clin. Nutr. Metab. Care 1, 217–224 [DOI] [PubMed] [Google Scholar]
  27. [30]30. Han D. M., Zhang Y. Q., Bai Q. X., Chen X. Q. (2007) Assay of AVP, CRP, and LPS in leukemia. Int. J. Lab. Hematol. 29, 185–189 [DOI] [PubMed] [Google Scholar]
  28. [31]31. Niebauer J., Volk H. D., Kemp M., Dominguez M., Schumann R. R., Rauchhaus M., Poole-Wilson P. A., Coats A. J., Anker S. D. (1999) Endotoxin and immune activation in chronic heart failure: a prospective cohort study. Lancet 353, 1838–1842 [DOI] [PubMed] [Google Scholar]
  29. [32]32. Al-Attas O. S., Al-Daghri N. M., Al-Rubeaan K., da Silva N. F., Sabico S. L., Kumar S., McTernan P. G., Harte A. L. (2009) Changes in endotoxin levels in T2DM subjects on anti-diabetic therapies. Cardiovasc. Diabetol. 8, 20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. [33]33. Takeda K., Akira S. (2001) Regulation of innate immune responses by Toll-like receptors. Jpn. J. Infect. Dis. 54, 209–219 [PubMed] [Google Scholar]
  31. [34]34. Janssens S., Beyaert R. (2003) Role of Toll-like receptors in pathogen recognition. Clin. Microbiol. Rev. 16, 637–646 [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. [36]36. Takeda K., Akira S. (2004) TLR signaling pathways. Semin. Immunol. 16, 3–9 [DOI] [PubMed] [Google Scholar]
  33. [37]37. Xu Y., Liu X. D., Gong X., Eissa N. T. (2008) Signaling pathway of autophagy associated with innate immunity. Autophagy 4, 110–112 [DOI] [PubMed] [Google Scholar]
  34. [38]38. Moylan J. S., Reid M. B. (2007) Oxidative stress, chronic disease, and muscle wasting. Muscle Nerve 35, 411–429 [DOI] [PubMed] [Google Scholar]
  35. [39]39. Lang C. H., Silvis C., Deshpande N., Nystrom G., Frost R. A. (2003) Endotoxin stimulates in vivo expression of inflammatory cytokines tumor necrosis factor alpha, interleukin-1beta, -6, and high-mobility-group protein-1 in skeletal muscle. Shock 19, 538–546 [DOI] [PubMed] [Google Scholar]
  36. [40]40. Boyd J. H., Divangahi M., Yahiaoui L., Gvozdic D., Qureshi S., Petrof B. J. (2006) Toll-like receptors differentially regulate CC and CXC chemokines in skeletal muscle via NF-κB and calcineurin. Infect. Immun. 74, 6829–6838 [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. [41]41. Xu Y., Jagannath C., Liu X. D., Sharafkhaneh A., Kolodziejska K. E., Eissa N. T. (2007) Toll-like receptor 4 is a sensor for autophagy associated with innate immunity. Immunity 27, 135–144 [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. [42]42. Mizushima N., Yamamoto A., Matsui M., Yoshimori T., Ohsumi Y. (2004) In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol. Biol. Cell 15, 1101–1111 [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. [43]43. Hoshino K., Takeuchi O., Kawai T., Sanjo H., Ogawa T., Takeda Y., Takeda K., Akira S. (1999) Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J. Immunol. 162, 3749–3752 [PubMed] [Google Scholar]
  40. [44]44. Thomas M., Lu J. J., Ge Q., Zhang C., Chen J., Klibanov A. M. (2005) Full deacylation of polyethylenimine dramatically boosts its gene delivery efficiency and specificity to mouse lung. Proc. Natl. Acad. Sci. U. S. A. 102, 5679–5684 [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. [45]45. Huang S., Jiang Y., Li Z., Nishida E., Mathias P., Lin S., Ulevitch R. J., Nemerow G. R., Han J. (1997) Apoptosis signaling pathway in T cells is composed of ICE/Ced-3 family proteases and MAP kinase kinase 6b. Immunity 6, 739–749 [DOI] [PubMed] [Google Scholar]
  42. [46]46. Menconi M., Gonnella P., Petkova V., Lecker S., Hasselgren P. O. (2008) Dexamethasone and corticosterone induce similar, but not identical, muscle wasting responses in cultured L6 and C2C12 myotubes. J. Cell. Biochem. 105, 353–364 [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. [47]47. Fulks R. M., Li J. B., Goldberg A. L. (1975) Effects of insulin, glucose, and amino acids on protein turnover in rat diaphragm. J. Biol. Chem. 250, 290–298 [PubMed] [Google Scholar]
  44. [48]48. Waalkes T. P., Udenfriend S. (1957) A fluorometric method for the estimation of tyrosine in plasma and tissues. J. Lab. Clin. Med. 50, 733–736 [PubMed] [Google Scholar]
  45. [49]49. Doan H. Q., Bowen K. A., Jackson L. A., Evers B. M. (2009) Toll-like receptor 4 activation increases Akt phosphorylation in colon cancer cells. Anticancer Res. 29, 2473–2478 [PMC free article] [PubMed] [Google Scholar]
  46. [50]50. Brunet A., Bonni A., Zigmond M. J., Lin M. Z., Juo P., Hu L. S., Anderson M. J., Arden K. C., Blenis J., Greenberg M. E. (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96, 857–868 [DOI] [PubMed] [Google Scholar]
  47. [51]51. Jin B., Li Y. P. (2007) Curcumin prevents lipopolysaccharide-induced atrogin-1/MAFbx upregulation and muscle mass loss. J. Cell. Biochem. 100, 960–969 [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. [52]52. Klionsky D. J., Abeliovich H., Agostinis P., Agrawal D. K., Aliev G., Askew D. S., Baba M., Baehrecke E. H., Bahr B. A., Ballabio A., Bamber B. A., Bassham D. C., Bergamini E., Bi X., Biard-Piechaczyk M., Blum J. S., Bredesen D. E., Brodsky J. L., Brumell J. H., Brunk U. T., Bursch W., Camougrand N., Cebollero E., Cecconi F., Chen Y., Chin L. S., Choi A., Chu C. T., Chung J., Clarke P. G., Clark R. S., Clarke S. G., Clavé C., Cleveland J. L., Codogno P., Colombo M. I., Coto-Montes A., Cregg J. M., Cuervo A. M., Debnath J., Demarchi F., Dennis P. B., Dennis P. A., Deretic V., Devenish R. J., Di Sano F., Dice J. F., Difiglia M., Dinesh-Kumar S., Distelhorst C. W., Djavaheri-Mergny M., Dorsey F. C., Dröge W., Dron M., Dunn W. A., Jr., Duszenko M., Eissa N. T., Elazar Z., Esclatine A., Eskelinen E. L., Fésüs L., Finley K. D., Fuentes J. M., Fueyo J., Fujisaki K., Galliot B., Gao F. B., Gewirtz D. A., Gibson S. B., Gohla A., Goldberg A. L., Gonzalez R., González-Estévez C., Gorski S., Gottlieb R. A., Häussinger D., He Y. W., Heidenreich K., Hill J. A., Høyer-Hansen M., Hu X., Huang W. P., Iwasaki A., Jäättelä M., Jackson W. T., Jiang X., Jin S., Johansen T., Jung J. U., Kadowaki M., Kang C., Kelekar A., Kessel D. H., Kiel J. A., Kim H. P., Kimchi A., Kinsella T. J., Kiselyov K., Kitamoto K., Knecht E., Komatsu M., Kominami E., Kondo S., Kovács A. L., Kroemer G., Kuan C. Y., Kumar R., Kundu M., Landry J., Laporte M., Le W., Lei H. Y., Lenardo M. J., Levine B., Lieberman A., Lim K. L., Lin F. C., Liou W., Liu L. F., Lopez-Berestein G., López-Otín C., Lu B., Macleod K. F., Malorni W., Martinet W., Matsuoka K., Mautner J., Meijer A. J., Meléndez A., Michels P., Miotto G., Mistiaen W. P., Mizushima N., Mograbi B., Monastyrska I., Moore M. N., Moreira P. I., Moriyasu Y., Motyl T., Münz C., Murphy L. O., Naqvi N. I., Neufeld T. P., Nishino I., Nixon R. A., Noda T., Nürnberg B., Ogawa M., Oleinick N. L., Olsen L. J., Ozpolat B., Paglin S., Palmer G. E., Papassideri I., Parkes M., Perlmutter D. H., Perry G., Piacentini M., Pinkas-Kramarski R., Prescott M., Proikas-Cezanne T., Raben N., Rami A., Reggiori F., Rohrer B., Rubinsztein D. C., Ryan K. M., Sadoshima J., Sakagami H., Sakai Y., Sandri M., Sasakawa C., Sass M., Schneider C., Seglen P. O., Seleverstov O., Settleman J., Shacka J. J., Shapiro I. M., Sibirny A., Silva-Zacarin E. C., Simon H. U., Simone C., Simonsen A., Smith M. A., Spanel-Borowski K., Srinivas V., Steeves M., Stenmark H., Stromhaug P. E., Subauste C. S., Sugimoto S., Sulzer D., Suzuki T., Swanson M. S., Tabas I., Takeshita F., Talbot N. J., Tallóczy Z., Tanaka K., Tanaka K., Tanida I., Taylor G. S., Taylor J. P., Terman A., Tettamanti G., Thompson C. B., Thumm M., Tolkovsky A. M., Tooze S. A., Truant R., Tumanovska L. V., Uchiyama Y., Ueno T., Uzcátegui N. L., van der Klei I., Vaquero E. C., Vellai T., Vogel M. W., Wang H. G., Webster P., Wiley J. W., Xi Z., Xiao G., Yahalom J., Yang J. M., Yap G., Yin X. M., Yoshimori T., Yu L., Yue Z., Yuzaki M., Zabirnyk O., Zheng X., Zhu X., Deter R. L. (2008) Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 4, 151–175 [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. [53]53. Seglen P. O., Gordon P. B. (1982) 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc. Natl. Acad. Sci. U. S. A. 79, 1889–1892 [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. [54]54. Li Y. P., Chen Y., Li A. S., Reid M. B. (2003) Hydrogen peroxide stimulates ubiquitin-conjugating activity and expression of genes for specific E2 and E3 proteins in skeletal muscle myotubes. Am. J. Physiol. Cell Physiol. 285, C806–C812 [DOI] [PubMed] [Google Scholar]
  51. [55]55. Tsan M. F., Gao B. (2004) Endogenous ligands of Toll-like receptors. J. Leukoc. Biol. 76, 514–519 [DOI] [PubMed] [Google Scholar]
  52. [56]56. Ehrchen J. M., Sunderkotter C., Foell D., Vogl T., Roth J. (2009) The endogenous Toll-like receptor 4 agonist S100A8/S100A9 (calprotectin) as innate amplifier of infection, autoimmunity, and cancer. J. Leukoc. Biol. 86, 557–566 [DOI] [PubMed] [Google Scholar]

Authors
Doyle, A., Zhang, G., Fattah, E. A. A., Eissa, N. T., & Li, Y.
Affiliations
  • The University of Texas Health Science Center at Houston (US)
  • Baylor College of Medicine (US)
Corresponding author
Li, Yi‐Ping
ORCID
Venue
The FASEB Journal
Publisher
Wiley
Published
2010-09-08
Volume
25
Issue
1
Pages
99-110
ISSN
  • 0892-6638 (ISSN-L)
  • 1530-6860
DOI
10.1096/fj.10-164152
PMC
PMC3005430
OpenAlex
W2055864551
Cited by
256
References
57
Citations by year
2026: 20 · 2025: 19 · 2024: 17 · 2023: 14 · 2022: 19 · 2021: 22 · 2020: 14 · 2019: 14 · 2018: 18 · 2017: 11 · 2016: 21 · 2015: 14 · 2014: 14 · 2013: 12 · 2012: 22
FWCI
5.08
Type
journal article
Language
en
Open access
Licence
Locations
  • The FASEB Journal (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR052511)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
Keywords
TLR4, lipopolysaccharide, muscle catabolism, muscle atrophy, cachexia, ubiquitin-proteasome system, autophagy-lysosome pathway, atrogin-1/MAFbx, MuRF1, p38 MAPK, 3-methyladenine, lactacystin, inflammation
MeSH terms
Animals, Autophagy, Cell Line, Enzyme Inhibitors, Imidazoles, Lipopolysaccharides, Lysosomes, Male, Mice, Inbred C57BL, Muscle Proteins, Muscles, Muscular Atrophy, Phagosomes, Pyridines, Blotting, Western, Signal Transduction, Mice, Knockout, Muscle Fibers, Skeletal, Ubiquitin, RNA Interference, SKP Cullin F-Box Protein Ligases, Proteasome Endopeptidase Complex, p38 Mitogen-Activated Protein Kinases, Toll-Like Receptor 4, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review