전체메뉴
검색
Article Search

JMB Journal of Microbiolog and Biotechnology

QR Code QR Code

Research article

References

  1. Singh SD, Robbins N, Zaas AK, Schell WA, Perfect JR, Cowen LE. 2009. Hsp90 governs echinocandin resistance in the pathogenic yeast Candida albicans via calcineurin. PLoS Pathog. 5: e1000532.
    Pubmed PMC CrossRef
  2. O’Meara TR, Veri AO, Polvi EJ, Li X, Valaei SF, Diezmann S, et al. 2016. Mapping the Hsp90 genetic network reveals ergosterol biosynthesis and phosphatidylinositol-4-kinase signaling as core circuitry governing cellular stress. PLoS Genet. 12: e1006142.
    Pubmed PMC CrossRef
  3. Shapiro RS, Robbins N, Cowen LE. 2011. Regulatory circuitry governing fungal development, drug resistance, and disease. Microbiol. Mol. Biol. Rev. 75: 213-267.
    CrossRef
  4. Cruz MC, Goldstein AL, Blankenship JR, Del PM, Davis D, Cardenas ME, et al. 2002. Calcineurin is essential for survival during membrane stress in Candida albicans. EMBO J. 21: 546-559.
    Pubmed PMC CrossRef
  5. Blankenship JR, Wormley FL, Boyce MK, Schell WA, Filler SG, Perfect JR, et al. 2003. Calcineurin is essential for Candida albicans survival in serum and virulence. Eukaryot. Cell 2: 422-430.
    Pubmed PMC CrossRef
  6. Uppuluri P, Nett J, Heitman J, Andes D. 2008. Synergistic effect of calcineurin inhibitors and fluconazole against Candida albicans biofilms. Antimicrob. Agents Chemother. 52: 1127-1132.
    Pubmed PMC CrossRef
  7. Cordeiro RA, Macedo RB, Teixeira CE, Marques FJ, Bandeira TJ, Moreira JL, et al. 2014. The calcineurin inhibitor cyclosporin A exhibits synergism with antifungals against Candida parapsilosis species complex. J. Med. Microbiol. 63:936-944.
    Pubmed CrossRef
  8. Yu SJ, Chang YL, Chen YL. 2015. Calcineurin signaling:lessons from Candida species. FEMS Yeast Res. 15: v16.
    Pubmed CrossRef
  9. Fried LE, Arbiser JL. 2009. Honokiol, a multifunctional antiangiogenic and antitumor agent. Antioxid. Redox Signal. 11: 1139-1148.
    Pubmed PMC CrossRef
  10. Sun L, Liao K, Hang C, Wang D. 2017. Honokiol induces reactive oxygen species-mediated apoptosis in Candida albicans through mitochondrial dysfunction. PLoS One 12:e172228.
    CrossRef
  11. Sun L, Liao K, Wang D. 2017. Honokiol induces superoxide production by targeting mitochondrial respiratory chain complex I in Candida albicans. PLoS One 12: e184003.
    CrossRef
  12. Clinical and Laboratory Standards Institute (CLSI). 2008. Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved Standard, M27-A3, 3rd Ed. Clinical and Laboratory Standards Institute, Wayne, PA.
  13. Sun L, Hang C, Liao K. 2018. Synergistic effect of caffeic acid phenethyl ester with caspofungin against Candida albicans is mediated by disrupting iron homeostasis. Food Chem. Toxicol. 116: 51-58.
    Pubmed CrossRef
  14. Sun LM, Liao K. 2018. Saccharomyces cerevisiae Hog1 MAP kinase pathway is activated in response to honokiol exposure. J. Appl. Microbiol. 124: 754-763.
    Pubmed CrossRef
  15. Wu XZ, Chang WQ, Cheng AX, Sun LM, Lou HX. 2010. Plagiochin E, an antifungal active macrocyclic bis(bibenzyl), induced apoptosis in Candida albicans through a metacaspasedependent apoptotic pathway. Biochim. Biophys. Acta 1800:439-447.
    Pubmed CrossRef
  16. Marchetti O, Moreillon P, Entenza JM, Vouillamoz J, Glauser MP, Bille J, et al. 2003. Fungicidal synergism of fluconazole and cyclosporine in Candida albicans is not dependent on multidrug efflux transporters encoded by the CDR1, CDR2, CaMDR1, and FLU1 genes. Antimicrob. Agents Chemother. 47: 1565-1570.
    CrossRef
  17. van Engeland M, Ramaekers FC, Schutte B, Reutelingsperger CP. 1996. A novel assay to measure loss of plasma membrane asymmetry during apoptosis of adherent cells in culture. Cytometry 24: 131-139.
    CrossRef
  18. Broekemeier KM, Dempsey ME, Pfeiffer DR. 1989. Cyclosporin A is a potent inhibitor of the inner membrane permeability transition in liver mitochondria. J. Biol. Chem. 264: 7826-7830.
    Pubmed
  19. Nicolli A, Basso E, Petronilli V, Wenger RM, Bernardi P. 1996. Interactions of cyclophilin with the mitochondrial inner membrane and regulation of the permeability transition pore, and cyclosporin A-sensitive channel. J. Biol. Chem. 271: 2185-2192.
    Pubmed CrossRef
  20. Zhao Y, Wang ZB, Xu JX. 2003. Effect of cytochrome c on the generation and elimination of O2·- and H2O2 in mitochondria. J. Biol. Chem. 278: 2356-2360.
    Pubmed CrossRef
  21. Waterhouse NJ, Trapani JA. 2003. A new quantitative assay for cytochrome c release in apoptotic cells. Cell Death Differ. 10: 853-855.
    Pubmed CrossRef
  22. Cowen LE, Singh SD, Kohler JR, Collins C, Zaas AK, Schell WA, et al. 2009. Harnessing Hsp90 function as a powerful, broadly effective therapeutic strategy for fungal infectious disease. Proc. Natl. Acad. Sci. USA 106: 2818-2823.
    Pubmed PMC CrossRef
  23. Koehn FE, Carter GT. 2005. The evolving role of natural products in drug discovery. Nat. Rev. Drug Discov. 4: 206-220.
    Pubmed CrossRef
  24. Woodbury A, Yu SP, Wei L, Garcia P. 2013. Neuromodulating effects of honokiol: a review. Front. Neurol. 4: 130.
    Pubmed PMC CrossRef
  25. Pan J, Lee Y, Wang Y, You M. 2016. Honokiol targets mitochondria to halt cancer progression and metastasis. Mol. Nutr. Food Res. 60: 1383-1395.
    Pubmed CrossRef
  26. Juvvadi PR, Lamoth F, Steinbach WJ. 2014. Calcineurin as a multifunctional regulator: unraveling novel functions in fungal stress responses, hyphal growth, drug resistance, and pathogenesis. Fungal Biol. Rev. 28: 56-69.
    CrossRef
  27. Palacin M, Coto E, Llobet L, Pacheu-Grau D, Montoya J, Ruiz-Pesini E. 2013. FK506 affects mitochondrial protein synthesis and oxygen consumption in human cells. Cell Biol. Toxicol. 29: 407-414.
    Pubmed CrossRef
  28. Almeida S, Domingues A, Rodrigues L, Oliveira CR, Rego AC. 2004. FK506 prevents mitochondrial-dependent apoptotic cell death induced by 3-nitropropionic acid in rat primary cortical cultures. Neurobiol. Dis. 17: 435-444.
    Pubmed CrossRef

Related articles in JMB

More Related Articles

Article

Research article

J. Microbiol. Biotechnol. 2018; 28(7): 1086-1093

Published online July 28, 2018 https://doi.org/10.4014/jmb.1801.01024

Copyright © The Korean Society for Microbiology and Biotechnology.

Roles of the Hsp90-Calcineurin Pathway in the Antifungal Activity of Honokiol

Kai Liao 1 and Lingmei Sun 2*

1Department of Pathology and Pathophysiology, Medical School of Southeast University, Nanjing 210009, P.R. China, 2Department of Pharmacology, Medical School of Southeast University, Nanjing 210009, P.R. China

Received: January 19, 2018; Accepted: April 30, 2018

Abstract

Honokiol, a bioactive compound isolated from the cone and bark of Magnolia officinalis, has
been shown to have various activities including inhibition of the growth of Candida albicans.
We investigated the roles of the Hsp90-calcineurin pathway in the antifungal activity of
honokiol. The pharmacologic tool was employed to evaluate the effects of Hsp90 and
calcineurin in the antifungal activity of honokiol. We also evaluated the protective effects of
the calcineurin inhibitor cyclosporin A (CsA) on honokiol-induced mitochondrial dysfunction
by the fluorescence staining method. The Hsp90 inhibitor potentiated the antifungal activity of
honokiol. A C. albicans strain with the calcineurin gene deleted displayed enhanced sensitivity
to honokiol. However, co-treatment with calcineurin inhibitor CsA attenuated the cytotoxic
activity of honokiol due to the protective effect on mitochondria. Our results provide insight
into the action mechanism of honokiol.

Keywords: Candida albicans, honokiol, HSP90, calcineurin, cyclosporin A, mitochondria

References

  1. Singh SD, Robbins N, Zaas AK, Schell WA, Perfect JR, Cowen LE. 2009. Hsp90 governs echinocandin resistance in the pathogenic yeast Candida albicans via calcineurin. PLoS Pathog. 5: e1000532.
    Pubmed KoreaMed CrossRef
  2. O’Meara TR, Veri AO, Polvi EJ, Li X, Valaei SF, Diezmann S, et al. 2016. Mapping the Hsp90 genetic network reveals ergosterol biosynthesis and phosphatidylinositol-4-kinase signaling as core circuitry governing cellular stress. PLoS Genet. 12: e1006142.
    Pubmed KoreaMed CrossRef
  3. Shapiro RS, Robbins N, Cowen LE. 2011. Regulatory circuitry governing fungal development, drug resistance, and disease. Microbiol. Mol. Biol. Rev. 75: 213-267.
    CrossRef
  4. Cruz MC, Goldstein AL, Blankenship JR, Del PM, Davis D, Cardenas ME, et al. 2002. Calcineurin is essential for survival during membrane stress in Candida albicans. EMBO J. 21: 546-559.
    Pubmed KoreaMed CrossRef
  5. Blankenship JR, Wormley FL, Boyce MK, Schell WA, Filler SG, Perfect JR, et al. 2003. Calcineurin is essential for Candida albicans survival in serum and virulence. Eukaryot. Cell 2: 422-430.
    Pubmed KoreaMed CrossRef
  6. Uppuluri P, Nett J, Heitman J, Andes D. 2008. Synergistic effect of calcineurin inhibitors and fluconazole against Candida albicans biofilms. Antimicrob. Agents Chemother. 52: 1127-1132.
    Pubmed KoreaMed CrossRef
  7. Cordeiro RA, Macedo RB, Teixeira CE, Marques FJ, Bandeira TJ, Moreira JL, et al. 2014. The calcineurin inhibitor cyclosporin A exhibits synergism with antifungals against Candida parapsilosis species complex. J. Med. Microbiol. 63:936-944.
    Pubmed CrossRef
  8. Yu SJ, Chang YL, Chen YL. 2015. Calcineurin signaling:lessons from Candida species. FEMS Yeast Res. 15: v16.
    Pubmed CrossRef
  9. Fried LE, Arbiser JL. 2009. Honokiol, a multifunctional antiangiogenic and antitumor agent. Antioxid. Redox Signal. 11: 1139-1148.
    Pubmed KoreaMed CrossRef
  10. Sun L, Liao K, Hang C, Wang D. 2017. Honokiol induces reactive oxygen species-mediated apoptosis in Candida albicans through mitochondrial dysfunction. PLoS One 12:e172228.
    CrossRef
  11. Sun L, Liao K, Wang D. 2017. Honokiol induces superoxide production by targeting mitochondrial respiratory chain complex I in Candida albicans. PLoS One 12: e184003.
    CrossRef
  12. Clinical and Laboratory Standards Institute (CLSI). 2008. Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved Standard, M27-A3, 3rd Ed. Clinical and Laboratory Standards Institute, Wayne, PA.
  13. Sun L, Hang C, Liao K. 2018. Synergistic effect of caffeic acid phenethyl ester with caspofungin against Candida albicans is mediated by disrupting iron homeostasis. Food Chem. Toxicol. 116: 51-58.
    Pubmed CrossRef
  14. Sun LM, Liao K. 2018. Saccharomyces cerevisiae Hog1 MAP kinase pathway is activated in response to honokiol exposure. J. Appl. Microbiol. 124: 754-763.
    Pubmed CrossRef
  15. Wu XZ, Chang WQ, Cheng AX, Sun LM, Lou HX. 2010. Plagiochin E, an antifungal active macrocyclic bis(bibenzyl), induced apoptosis in Candida albicans through a metacaspasedependent apoptotic pathway. Biochim. Biophys. Acta 1800:439-447.
    Pubmed CrossRef
  16. Marchetti O, Moreillon P, Entenza JM, Vouillamoz J, Glauser MP, Bille J, et al. 2003. Fungicidal synergism of fluconazole and cyclosporine in Candida albicans is not dependent on multidrug efflux transporters encoded by the CDR1, CDR2, CaMDR1, and FLU1 genes. Antimicrob. Agents Chemother. 47: 1565-1570.
    CrossRef
  17. van Engeland M, Ramaekers FC, Schutte B, Reutelingsperger CP. 1996. A novel assay to measure loss of plasma membrane asymmetry during apoptosis of adherent cells in culture. Cytometry 24: 131-139.
    CrossRef
  18. Broekemeier KM, Dempsey ME, Pfeiffer DR. 1989. Cyclosporin A is a potent inhibitor of the inner membrane permeability transition in liver mitochondria. J. Biol. Chem. 264: 7826-7830.
    Pubmed
  19. Nicolli A, Basso E, Petronilli V, Wenger RM, Bernardi P. 1996. Interactions of cyclophilin with the mitochondrial inner membrane and regulation of the permeability transition pore, and cyclosporin A-sensitive channel. J. Biol. Chem. 271: 2185-2192.
    Pubmed CrossRef
  20. Zhao Y, Wang ZB, Xu JX. 2003. Effect of cytochrome c on the generation and elimination of O2·- and H2O2 in mitochondria. J. Biol. Chem. 278: 2356-2360.
    Pubmed CrossRef
  21. Waterhouse NJ, Trapani JA. 2003. A new quantitative assay for cytochrome c release in apoptotic cells. Cell Death Differ. 10: 853-855.
    Pubmed CrossRef
  22. Cowen LE, Singh SD, Kohler JR, Collins C, Zaas AK, Schell WA, et al. 2009. Harnessing Hsp90 function as a powerful, broadly effective therapeutic strategy for fungal infectious disease. Proc. Natl. Acad. Sci. USA 106: 2818-2823.
    Pubmed KoreaMed CrossRef
  23. Koehn FE, Carter GT. 2005. The evolving role of natural products in drug discovery. Nat. Rev. Drug Discov. 4: 206-220.
    Pubmed CrossRef
  24. Woodbury A, Yu SP, Wei L, Garcia P. 2013. Neuromodulating effects of honokiol: a review. Front. Neurol. 4: 130.
    Pubmed KoreaMed CrossRef
  25. Pan J, Lee Y, Wang Y, You M. 2016. Honokiol targets mitochondria to halt cancer progression and metastasis. Mol. Nutr. Food Res. 60: 1383-1395.
    Pubmed CrossRef
  26. Juvvadi PR, Lamoth F, Steinbach WJ. 2014. Calcineurin as a multifunctional regulator: unraveling novel functions in fungal stress responses, hyphal growth, drug resistance, and pathogenesis. Fungal Biol. Rev. 28: 56-69.
    CrossRef
  27. Palacin M, Coto E, Llobet L, Pacheu-Grau D, Montoya J, Ruiz-Pesini E. 2013. FK506 affects mitochondrial protein synthesis and oxygen consumption in human cells. Cell Biol. Toxicol. 29: 407-414.
    Pubmed CrossRef
  28. Almeida S, Domingues A, Rodrigues L, Oliveira CR, Rego AC. 2004. FK506 prevents mitochondrial-dependent apoptotic cell death induced by 3-nitropropionic acid in rat primary cortical cultures. Neurobiol. Dis. 17: 435-444.
    Pubmed CrossRef