Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Conessine Treatment Reduces Dexamethasone-Induced Muscle Atrophy by Regulating MuRF1 and Atrogin-1 Expression

  • Kim, Hyunju (Division of Biological Science and Technology, Yonsei University) ;
  • Jang, Minsu (Division of Biological Science and Technology, Yonsei University) ;
  • Park, Rackhyun (Division of Biological Science and Technology, Yonsei University) ;
  • Jo, Daum (Division of Biological Science and Technology, Yonsei University) ;
  • Choi, Inho (Division of Biological Science and Technology, Yonsei University) ;
  • Choe, Joonho (Department of Biological Sciences, Korea Advanced Institute of Science and Technology) ;
  • Oh, Won Keun (Korea Bioactive Natural Material Bank, College of Pharmacy, Seoul National University) ;
  • Park, Junsoo (Division of Biological Science and Technology, Yonsei University)
  • Received : 2017.11.07
  • Accepted : 2018.01.22
  • Published : 2018.04.28
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Abstract

Conessine, a steroidal alkaloid, is a potent histamine H3 antagonist with antimalarial activity. We recently reported that conessine treatment interferes with $H_2O_2$-induced cell death by regulating autophagy. However, the cellular signaling pathways involved in conessine treatment are not fully understood. Here, we report that conessine reduces muscle atrophy by interfering with the expression of atrophy-related ubiquitin ligases MuRF-1 and atrogin-1. Promoter reporter assay revealed that conessine treatment inhibits FoxO3a-dependent transcription, $NF-{\kappa}B$-dependent transcription, and p53-dependent transcription. We also showed by quantitative RT-PCR and western blot assays that conessine treatment reduced dexamethasone-induced expression of MuRF1 and atrogin-1. Finally, we demonstrated that conessine treatment reduced dexamethasone-induced muscle atrophy using differentiated C2C12 cells. These results collectively suggest that conessine is potentially useful in the treatment of muscle atrophy.

Keywords

References

  1. Bodine SC, Baehr LM. 2014. Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1. Am. J. Physiol. Endocrinol. Metab. 307: E469-E484. https://doi.org/10.1152/ajpendo.00204.2014
  2. Attaix D, Baracos VE. 2010. MAFbx/Atrogin-1 expression is a poor index of muscle proteolysis. Curr. Opin. Clin. Nutr. Metab. Care 13: 223-224. https://doi.org/10.1097/MCO.0b013e328338b9a6
  3. Fitts RH, Riley DR, Widrick JJ. 2001. Functional and structural adaptations of skeletal muscle to microgravity. J. Exp. Biol. 204: 3201-3208.
  4. Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, et al. 2001. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294: 1704-1708. https://doi.org/10.1126/science.1065874
  5. Clarke BA, Drujan D, Willis MS, Murphy LO, Corpina RA, Burova E, et al. 2007. The E3 ligase MuRF1 degrades myosin heavy chain protein in dexamethasone-treated skeletal muscle. Cell Metab. 6: 376-385. https://doi.org/10.1016/j.cmet.2007.09.009
  6. Sacheck JM, Ohtsuka A, McLary SC, Goldberg AL. 2004. IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1. Am. J. Physiol. Endocrinol. Metab. 287: E591-E601. https://doi.org/10.1152/ajpendo.00073.2004
  7. Senf SM, Dodd SL, McClung JM, Judge AR. 2008. Hsp70 overexpression inhibits NF-kappaB and Foxo3a transcriptional activities and prevents skeletal muscle atrophy. FASEB J. 22: 3836-3845. https://doi.org/10.1096/fj.08-110163
  8. Wu CL, Cornwell EW, Jackman RW, Kandarian SC. 2014. NF-kappaB but not FoxO sites in the MuRF1 promoter are required for transcriptional activation in disuse muscle atrophy. Am. J. Physiol. Cell Physiol. 306: C762-C767. https://doi.org/10.1152/ajpcell.00361.2013
  9. Adams V, Mangner N, Gasch A, Krohne C, Gielen S, Hirner S, et al. 2008. Induction of MuRF1 is essential for TNF-alpha-induced loss of muscle function in mice. J. Mol. Biol. 384: 48-59. https://doi.org/10.1016/j.jmb.2008.08.087
  10. Atherton PJ, Greenhaff PL, Phillips SM, Bodine SC, Adams CM, Lang CH. 2016. Control of skeletal muscle atrophy in response to disuse: clinical/preclinical contentions and fallacies of evidence. Am. J. Physiol. Endocrinol. Metab. 311: E594-E604. https://doi.org/10.1152/ajpendo.00257.2016
  11. Dua VK, Verma G, Singh B, Rajan A, Bagai U, Agarwal DD, et al. 2013. Anti-malarial property of steroidal alkaloid conessine isolated from the bark of Holarrhena antidysenterica. Malar. J. 12: 194. https://doi.org/10.1186/1475-2875-12-194
  12. Zirihi GN, Grellier P, Guede-Guina F, Bodo B, Mambu L. 2005. Isolation, characterization and antiplasmodial activity of steroidal alkaloids from Funtumia elastica (Preuss) Stapf. Bioorg. Med. Chem. Lett. 15: 2637-2640. https://doi.org/10.1016/j.bmcl.2005.03.021
  13. Paris R. 1951. [On a new acquisition in phytotherapy: Holarrhena floribunda and its principal alkaloid: conessine]. Gaz. Med. Fr. Spec. No.: 79-83.
  14. Zhao C, Sun M, Bennani YL, Gopalakrishnan SM, Witte DG, Miller TR, et al. 2008. The alkaloid conessine and analogues as potent histamine H3 receptor antagonists. J. Med. Chem. 51: 5423-5430. https://doi.org/10.1021/jm8003625
  15. Kim H, Lee KI, Jang M, Namkoong S, Park R, Ju H, et al. 2016. Conessine interferes with oxidative stress-induced C2C12 myoblast cell death through inhibition of autophagic flux. PLoS One 11: e0157096. https://doi.org/10.1371/journal.pone.0157096
  16. Zhou C, Liu J. 2003. Inhibition of human telomerase reverse transcriptase gene expression by BRCA1 in human ovarian cancer cells. Biochem. Biophys. Res. Commun. 303: 130-136. https://doi.org/10.1016/S0006-291X(03)00318-8
  17. Paumelle R, Tulasne D, Kherrouche Z, Plaza S, Leroy C, Reveneau S, et al. 2002. Hepatocyte growth factor/scatter factor activates the ETS1 transcription factor by a RAS-RAF-MEK-ERK signaling pathway. Oncogene 21: 2309-2319. https://doi.org/10.1038/sj.onc.1205297
  18. Park J, Kim K, Lee EJ, Seo YJ, Lim SN, Park K, et al. 2007. Elevated level of SUMOylated IRF-1 in tumor cells interferes with IRF-1-mediated apoptosis. Proc. Natl. Acad. Sci. USA 104: 17028-17033. https://doi.org/10.1073/pnas.0609852104
  19. Kimbrel EA, Kung AL. 2009. The F-box protein beta-TrCp1/Fbw1a interacts with p300 to enhance beta-catenin transcriptional activity. J. Biol. Chem. 284: 13033-13044. https://doi.org/10.1074/jbc.M901248200
  20. Datto MB, Li Y, Panus JF, Howe DJ, Xiong Y, Wang XF. 1995. Transforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism. Proc. Natl. Acad. Sci. USA 92: 5545-5549. https://doi.org/10.1073/pnas.92.12.5545
  21. Namkoong S, Kim TJ, Jang IS, Kang KW, Oh WK, Park J. 2011. Alpinumisoflavone induces apoptosis and suppresses extracellular signal-regulated kinases/mitogen activated protein kinase and nuclear factor-kappaB pathways in lung tumor cells. Biol. Pharm. Bull. 34: 203-208. https://doi.org/10.1248/bpb.34.203
  22. Brunet A, Park J, Tran H, Hu LS, Hemmings BA, Greenberg ME. 2001. Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a). Mol. Cell. Biol. 21: 952-965. https://doi.org/10.1128/MCB.21.3.952-965.2001
  23. Sanchez AM, Csibi A, Raibon A, Cornille K, Gay S, Bernardi H, et al. 2012. AMPK promotes skeletal muscle autophagy through activation of forkhead FoxO3a and interaction with Ulk1. J. Cell. Biochem. 113: 695-710. https://doi.org/10.1002/jcb.23399
  24. Ni HM, Du K, You M, Ding WX. 2013. Critical role of FoxO3a in alcohol-induced autophagy and hepatotoxicity. Am. J. Pathol. 183: 1815-1825. https://doi.org/10.1016/j.ajpath.2013.08.011
  25. Murray-Zmijewski F, Slee EA, Lu X. 2008. A complex barcode underlies the heterogeneous response of p53 to stress. Nat. Rev. Mol. Cell Biol. 9: 702-712. https://doi.org/10.1038/nrm2451
  26. Datta K, Babbar P, Srivastava T, Sinha S, Chattopadhyay P. 2002. p53 dependent apoptosis in glioma cell lines in response to hydrogen peroxide induced oxidative stress. Int. J. Biochem. Cell Biol. 34: 148-157. https://doi.org/10.1016/S1357-2725(01)00106-6

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