Atg3-Mediated Lipidation of Atg8 Is Involved in Encystation of<i>Acanthamoeba</i>

Moon, Eun‐Kyung; Chung, Dong‐Il; Hong, Yeonchul; Kong, Hyun-Hee

doi:10.3347/kjp.2011.49.2.103

Cited by 24 publications

(31 citation statements)

References 20 publications

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“…In Acanthamoeba spp., Atg8 and Atg3 have been identified (Moon et al. ), but whether expression of these genes is upregulated during apoptosis in Acanthamoeba spp. is unknown.…”

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confidence: 99%

“…Moreover, autophagy is intimately linked with apoptosis and is governed by a set of autophagy-related genes (Atg) (Rubinstein et al 2011), with Atg 3, 5, 7, 8, 10, 12, and 16 required in cascade reactions that complete autophagosome assembly. In Acanthamoeba spp., Atg8 and Atg3 have been identified (Moon et al 2011), but whether expression of these genes is upregulated during apoptosis in Acanthamoeba spp. is unknown.…”

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confidence: 99%

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Apoptosis of Acanthamoeba castellanii Trophozoites Induced by Oleic Acid

Qiao

Feng

et al. 2017

J Eukaryotic Microbiology

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Acanthamoeba spp. can be parasitic in certain situations and are responsible for serious human infections, including Acanthamoeba keratitis, granulomatous amoebic encephalitis, and cutaneous acanthamoebiasis. We analyzed the fatty acid composition of Acanthamoeba castellanii trophozoites and tested the inhibitory activity of the main fatty acids, oleic acid and arachidonic acid, in vitro. Oleic acid markedly inhibited the growth of A. castellanii, with trophozoite viability of 57.4% at a concentration of 200 μM. Caspase-3 staining and annexin V assays showed that apoptotic death occurred in A. castellanii trophozoites. Quantitative PCR and dot blot analysis showed increased levels of metacaspase and interleukin-1β converting enzyme, which is also an indication of apoptosis. In contrast, arachidonic acid showed negligible inhibition of growth of A. castellanii trophozoites. Stimulated expression of Atg3, Atg8 and LC3A/B genes and monodansylcadaverine labeling suggested that oleic acid induces apoptosis by triggering autophagy of trophozoites.

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“…In Acanthamoeba spp., Atg8 and Atg3 have been identified (Moon et al. ), but whether expression of these genes is upregulated during apoptosis in Acanthamoeba spp. is unknown.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Apoptosis of Acanthamoeba castellanii Trophozoites Induced by Oleic Acid

Qiao

Feng

et al. 2017

J Eukaryotic Microbiology

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“…The biological significance of autophagy associated with starvation, differentiation, development, and immunity has been previously demonstrated (10)(11)(12)(13). In Acanthamoeba cells, several genes associated with autophagy, including those encoding Atg8, Atg8 isoform, Atg3, and Atg16L, were identified and their roles in the encystation of Acanthamoeba cells were studied (14)(15)(16)(17). Autophagy is a major cellular pathway for the encystation of Acanthamoeba cells.…”

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confidence: 99%

Autophagy Inhibitors as a Potential Antiamoebic Treatment for Acanthamoeba Keratitis

Moon

Kim

Hong

et al. 2015

Antimicrob Agents Chemother

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bAcanthamoeba cysts are resistant to extreme physical and chemical conditions. Autophagy is an essential pathway for encystation of Acanthamoeba cells. To evaluate the possibility of an autophagic Acanthamoeba encystation mechanism, we evaluated autophagy inhibitors, such as 3-methyladenine (3MA), LY294002, wortmannin, bafilomycin A, and chloroquine. Among these autophagy inhibitors, the use of 3MA and chloroquine showed a significant reduction in the encystation ratio in Acanthamoeba cells. Wortmannin also inhibited the formation of mature cysts, while LY294002 and bafilomycin A did not affect the encystation of Acanthamoeba cells. Transmission electron microscopy revealed that 3MA and wortmannin inhibited autophagy formation and that chloroquine interfered with the formation of autolysosomes. Inhibition of autophagy or autolysosome formation resulted in a significant block in the encystation in Acanthamoeba cells. Clinical treatment with 0.02% polyhexamethylene biguanide (PHMB) showed high cytopathic effects on Acanthamoeba trophozoites and cysts; however, it also revealed high cytopathic effects on human corneal epithelial cells. In this study, we investigated effects of the combination of a low (0.00125%) concentration of PHMB with each of the autophagy inhibitors 3MA, wortmannin, and chloroquine on Acanthamoeba and human corneal epithelial cells. These new combination treatments showed low cytopathic effects on human corneal cells and high cytopathic effects on Acanthamoeba cells. Taken together, these results provide fundamental information for optimizing the treatment of Acanthamoeba keratitis.A canthamoeba trophozoites differentiate into cysts under conditions of physical stresses, starvation, and chemical exposure (1-3); the cysts are resistant to several chemical biocides (4). Resistance of the cysts to chemotherapeutic drugs makes the treatment of Acanthamoeba infections difficult (4, 5). Although polyhexamethylene biguanide (PHMB) (0.02%), alone or in combination with a diamidine (0.1% propamidine or 0.1% hexamidine), showed therapeutic efficacy against Acanthamoeba keratitis (6), PHMB was reported to be cytotoxic to human corneal epithelial (HCE) cells (7). Although therapy for Acanthamoeba keratitis needs better-acting drugs, due to the encystation of Acanthamoeba cells, cytotoxicity toward mammalian cells must also be considered.Recent studies have demonstrated anticancer therapies that include autophagy targeting in different tumor cell lines (8, 9). One change in the cellular composition during the encystation of protozoa is the formation of an autophagy (10). The biological significance of autophagy associated with starvation, differentiation, development, and immunity has been previously demonstrated (10-13). In Acanthamoeba cells, several genes associated with autophagy, including those encoding Atg8, Atg8 isoform, Atg3, and Atg16L, were identified and their roles in the encystation of Acanthamoeba cells were studied (14-17). Autophagy is a major cellular pathway for the encystation of Acanth...

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“…Previous reports of cyst-specific gene expression profiles suggest that autophagy genes are highly expressed and have crucial roles during encystation of A. castellanii (13,14,32). Accordingly, we speculated that inhibiting the autophagic process could block encystation of Acanthamoeba, ultimately leading to decreased cell viability.…”

Section: Resultsmentioning

confidence: 92%

Chloroquine Has a Cytotoxic Effect on Acanthamoeba Encystation through Modulation of Autophagy

Jha

Jung

Seo

et al. 2014

Antimicrob Agents Chemother

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bEncystation of Acanthamoeba castellanii is associated with resistance to chemotherapeutic agents. Blocking the encystation process could potentiate the efficacy of chemotherapeutic agents and biocides. During encystation, autophagy is highly stimulated and required for proper encystation of Acanthamoeba. In this study, the cytotoxic effect of chloroquine, a well-known autophagy-inhibitory drug, was tested in A. castellanii. Chloroquine was able to selectively reduce cell survival during the encystation of A. castellanii. However, A. castellanii trophozoites and mature cysts were resistant to chloroquine. Chloroquine treatment led to an increase in the number and size of lysosomes in encysting cells. Moreover, chloroquine inhibited the degradation of long-lived proteins in the encysting cells. Decreased autophagic flux, indicated by an increased number of lysosomes and decreased degradation of long-lived proteins, may be the mechanism by which cell death is induced by chloroquine in encysting Acanthamoeba. These results suggest a potential novel therapeutic application of chloroquine as an anti-Acanthamoeba drug. Our findings also suggest that targeting autophagy could be a therapeutic strategy against Acanthamoeba infection.

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Atg3-Mediated Lipidation of Atg8 Is Involved in Encystation ofAcanthamoeba

Cited by 24 publications

References 20 publications

Apoptosis of Acanthamoeba castellanii Trophozoites Induced by Oleic Acid

Apoptosis of Acanthamoeba castellanii Trophozoites Induced by Oleic Acid

Autophagy Inhibitors as a Potential Antiamoebic Treatment for Acanthamoeba Keratitis

Chloroquine Has a Cytotoxic Effect on Acanthamoeba Encystation through Modulation of Autophagy

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