The antimicrobial peptide arenicin-1 promotes generation of reactive oxygen species and induction of apoptosis

Cho, Jae-Yong; Lee, Dong Gun

doi:10.1016/j.bbagen.2011.08.011

Cited by 76 publications

(65 citation statements)

References 36 publications

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“…Metacaspases are caspaselike cysteine proteases identified in yeasts, plants, and protozoa (27). These enzymes are closely associated with the generation of ROS and mitochondrial dysfunction (26). Caspase-like activity was measured in R. oryzae, C. bertholletiae, and M. circinelloides germlings pretreated with PCZ (0.125 to 4 g/ml) or ICZ (0.06 to 4 g/ml) in conjunction with TCR (0.015 g/ml) for 3 h at 37°C using the CaspACE FITC-benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (VAD-FMK) in situ marker (Promega, Madison, WI), according to the manufacturer's instructions (28).…”

Section: Methodsmentioning

confidence: 99%

“…DNA fragmentation, a characteristic change in apoptosis, was detected using a terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL) assay in R. oryzae, C. bertholletiae, and M. circinelloides (17,19,26). Cells pretreated with PCZ (R. oryzae, 0.125 to 0.5 g/ml; C. bertholletiae, 1 to 4 g/ml; M. circinelloides, 1 to 4 g/ml) or ICZ (R. oryzae, 0.06 to 0.25 g/ml; C. bertholletiae, 0.25 to 1 g/ml; M. circinelloides, 1 to 4 g/ml) in conjunction with TCR (0.015 g/ml) for 3 h at 37°C were fixed with 3.7% formaldehyde for 30 min on ice and were digested with the lysing enzyme mixture.…”

Section: Methodsmentioning

confidence: 99%

“…cyt c release from mitochondria. Translocation of mitochondrial cytochrome c (cyt c) to the cytosol is considered a critical event in apoptosis (26). For estimation of cyt c, isolation of mitochondria from R. oryzae, C. bertholletiae, and M. circinelloides germlings was performed according to the method described by Niimi et al (29).…”

Section: Methodsmentioning

confidence: 99%

“…ROS play important roles as early initiators of apoptosis in yeasts and other filamentous fungi (26). Intracellular ROS levels in R. oryzae germlings were measured using a fluorimetric assay with DHR-123 (Sigma) staining (17).…”

Section: Azoles (Pcz Icz) When Combined With Tcr Increase Intracelmentioning

confidence: 99%

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The Calcineurin Pathway Inhibitor Tacrolimus Enhances the In Vitro Activity of Azoles against Mucorales via Apoptosis

Shirazi

Kontoyiannis

2013

Eukaryot Cell

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The calcineurin pathway regulates antifungal drug resistance and the virulence of several major human-pathogenic fungi, including the recalcitrant Mucorales. We hypothesized that the fungistatic triazoles posaconazole (PCZ) and itraconazole (ICZ) become fungicidal in the setting of the calcineurin inhibitor tacrolimus (TCR) and that such an effect is mediated through apoptosis. Fungicidal activity and apoptosis were studied using standard microbiological techniques and hyphal metabolic and vital dye reduction assays at 37°C in RPMI 1640. Apoptosis was characterized by detecting intracellular Ca 2؉ , phosphatidylserine (PS) externalization, DNA fragmentation, plasma membrane integrity, chromatin condensation, reactive oxygen species (ROS) generation, caspase-like activity, ATP, and cytochrome c release. MICs for PCZ and ICZ alone were significantly higher (8 to 128 g/ml) than those of PCZ or ICZ plus TCR (0.25 to 4 g/ml) for Rhizopus oryzae, Cunninghamella bertholletiae, and Mucor circinelloides. Both PCZ and ICZ in combination with TCR became fungicidal, and their activity was mediated through increased apoptotic cell death of R. oryzae (10 to 50%), C. bertholletiae (5 to 50%), and M. circinelloides (5 to 55%) germlings, with morphological apoptotic changes characterized by externalization of PS, nuclear condensation, and DNA fragmentation. Moreover, activation of the caspase-like activity was correlated with cell death induced by TCR plus PCZ or ICZ. These changes correlated with elevated intracellular Ca 2؉ and ROS levels and disturbance of mitochondrial potential. We found that PCZ or ICZ in combination with TCR renders Mucorales sensitive to triazoles via apoptotic death. These observations could serve as a new paradigm for the development of new therapeutic strategies.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Azoles (Pcz Icz) When Combined With Tcr Increase Intracelmentioning

confidence: 99%

See 2 more Smart Citations

The Calcineurin Pathway Inhibitor Tacrolimus Enhances the In Vitro Activity of Azoles against Mucorales via Apoptosis

Shirazi

Kontoyiannis

2013

Eukaryot Cell

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“…20,21 7) (E) and CAS-NS C. parapsilosis (isolate 12) (F) treated with MICA. DIC: differential interference contrast; Ca: C. albicans; Cp: C. parapsilosis; C: untreated control.…”

Section: Resultsmentioning

confidence: 99%

Micafungin triggers caspase-dependent apoptosis inCandida albicansandCandida parapsilosisbiofilms, including caspofungin non-susceptible isolates

Shirazi

Kontoyiannis

2015

Virulence

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Candida biofilms play an important role in infections associated with medical devices and are resistant to antifungals. We hypothesized that the echinocandin micafungin (MICA) exerts an enhanced antifungal activity against caspofungin (CAS)-susceptible (CAS-S) and CAS-non-susceptible (CAS-NS) Candida albicans and Candida parapsilosis which is at least in part through apoptosis, even in the biofilm environment. Apoptosis was characterized by detecting reactive oxygen species (ROS) accumulation, depolarization of mitochondrial membrane potential (MMP), DNA fragmentation, lack of plasma membrane integrity, and metacaspase activation following exposure of Candida biofilm to MICA for 3h at 37 C in RPMI 1640 medium. The minimum inhibitory concentration was higher for CAS (2.0-16.0 mg/ mL) than for MICA (1.0-8.0 mg/mL) for Candida biofilms. Elevated intracellular ROS levels and depolarization of MMP was evident in CAS-S C. albicans (3.0-4.2 fold) and C. parapsilosis (4.8-5.4 fold) biofilms compared with CAS-NS (1.2 fold) after exposure to MICA (0.25x-1xMIC). Elevated intracellular ROS levels and depolarization of MMP was evident in CAS-S C. albicans (3.0-4.2 fold) and C. parapsilosis (4.8-5.4 fold) biofilms compared with CAS-NS (1.2 fold) after exposure to MICA (0.25x-1xMIC). Finally higher ß-1, 3 glucan levels were seen in sessile cells compared to planktonic cells, especially in CAS-NS strains. MICA treatment might induce a metacaspase-dependent apoptotic process in biofilms of both CAS-S C. albicans and C. parapsilosis, and to some degree in CAS-NS strains.

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Cecropin A-induced apoptosis is regulated by ion balance and glutathione antioxidant system inCandida albicans

Yun

Lee

2016

IUBMB Life

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Cecropin A, isolated from the giant silk moth Hyalophora cecropia, is a 37-mer peptide that exerts potent antimicrobial effects. We investigated cecropin A-induced apoptosis associated with ion balance and redox state of Candida albicans. The antifungal effect of cecropin A, associated with ion movement was verified by significant increase of cell viability following pretreatment of ion channel blockers. Cecropin A induced undesired ion movement such as calcium accumulation and potassium leakage. Furthermore, the reduction of phosphatidylserine (PS) externalization was detected following pretreatment of ion channel blockers. Based on these results, we confirmed that ion imbalance regulates the apoptotic activity of cecropin A. Moreover, cecropin A decreased NADPH and glutathione levels, which are crucial factors in the intracellular antioxidant defense system. The decreased intracellular antioxidant capacity induced oxidative stress by generating reactive oxygen species (ROS). Moreover, several apoptotic features such as mitochondrial depolarization, caspase activation, and DNA fragmentation were observed in cecropin A-treated cells. In conclusion, disrupted ion balance and intracellular glutathione redox state play a key role in cecropin A-induced apoptosis in C. albicans.

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The antimicrobial peptide arenicin-1 promotes generation of reactive oxygen species and induction of apoptosis

Cited by 76 publications

References 36 publications

The Calcineurin Pathway Inhibitor Tacrolimus Enhances the In Vitro Activity of Azoles against Mucorales via Apoptosis

The Calcineurin Pathway Inhibitor Tacrolimus Enhances the In Vitro Activity of Azoles against Mucorales via Apoptosis

Micafungin triggers caspase-dependent apoptosis inCandida albicansandCandida parapsilosisbiofilms, including caspofungin non-susceptible isolates

Cecropin A-induced apoptosis is regulated by ion balance and glutathione antioxidant system inCandida albicans

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