Entamoeba histolytica: Apoptosis induced in vitro by nitric oxide species

Ramos, Espiridión; Olivos-García, Alfonso; Néquiz, Mario; Saavedra, Emma; Tello, Eusebio; Saralegui, Andrés; Montfort, Irmgard; Tamayo, Ruy Pérez

doi:10.1016/j.exppara.2007.01.011

Cited by 50 publications

(53 citation statements)

References 33 publications

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“…We are reporting for the first time that Blastocystis ST-4 (WR-1) and ST-7 (B) are susceptible to nitrosative stress (Table 1). With the exception of NaNO 2 , 24 h of exposure to common NO donors killed both Blastocystis isolates at concentrations known to suppress growth of other parasites (8,33) (Table 1). Susceptibility to SNAP, GSNO, and NaNO 2 varied between the two isolates tested (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…The cytotoxicity and therapeutic potential of NO against a range of microbial agents are well established (20,30,33). NO prevents growth as well as encystation of Giardia (3), while it induces apoptosis-like features in Entamoeba (33).…”

Section: Discussionmentioning

confidence: 99%

“…Generation of nitrosative stress in response to microbes is also an important component of the human cellular defense arsenal (3,6,19). The antimicrobial activity of NO has been reported for a wide range of prokaryotic (24) and eukaryotic (20,30,33) organisms. A recent study suggested that NO also induces apoptosis-like cell death in Blastocystis (4).…”

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confidence: 99%

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A Metronidazole-Resistant Isolate of Blastocystis spp. Is Susceptible to Nitric Oxide and Downregulates Intestinal Epithelial Inducible Nitric Oxide Synthase by a Novel Parasite Survival Mechanism

et al. 2011

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Blastocystis, one of the most common parasites colonizing the human intestine, is an extracellular, noninvasive, luminal protozoan with controversial pathogenesis. Blastocystis infections can be asymptomatic or cause intestinal symptoms of vomiting, diarrhea, and abdominal pain. Although chronic infections are frequently reported, Blastocystis infections have also been reported to be self-limiting in immunocompetent patients. Characterizing the host innate response to Blastocystis would lead to a better understanding of the parasite's pathogenesis. Intestinal epithelial cells produce nitric oxide (NO), primarily on the apical side, in order to target luminal pathogens. In this study, we show that NO production by intestinal cells may be a host defense mechanism against Blastocystis. Two clinically relevant isolates of Blastocystis, ST-7 (B) and ST-4 (WR-1), were found to be susceptible to a range of NO donors. ST-7 (B), a metronidazole-resistant isolate, was found to be more sensitive to nitrosative stress. Using the Caco-2 model of human intestinal epithelium, Blastocystis ST-7 (B) but not ST-4 (WR-1) exhibited dose-dependent inhibition of Caco-2 NO production, and this was associated with downregulation of inducible nitric oxide synthase (iNOS). Despite its higher susceptibility to NO, Blastocystis ST-7 (B) may have evolved unique strategies to evade this potential host defense by depressing host NO production. This is the first study to highlight a strain-to-strain variation in the ability of Blastocystis to evade the host antiparasitic NO response.Blastocystis is an extracellular and noninvasive unicellular enteric parasite with zoonotic potential (28,41,42). It is among the most common parasites found in the human intestine, with prevalence ranging between 10% of the population in developed countries and 50% in developing countries (42). It is a species complex belonging to the Stramenopile group. According to a recent classification, it is divided into 11 subtypes, 9 of which are known to infect humans. Other common hosts are chickens, rats, pigs, reptiles, and insects (41). Despite recent advances in our understanding of the parasite's classification and pathobiology, several questions concerning the parasite's biology remain unanswered. The parasite's pathogenicity is also controversial owing to asymptomatic carriage, coinfection with other pathogens, and nonresponsiveness to conventional chemotherapeutic agents.Blastocystis infections or blastocystosis present with common intestinal symptoms, such as abdominal pain, vomiting, and bloating, as well as mucous and watery diarrhea (42). Dermatological disorders (15,45) and irritable bowel syndrome (39) are also frequently associated with Blastocystis infections. It is transmitted through the feco-oral route, and metronidazole is the treatment of choice for Blastocystis infections. The parasite has a high prevalence in immunocompromised individuals (17,29,43). In immunocompetent individuals, Blastocystis infections are often asymptomatic (7, 39) or self-limi...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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A Metronidazole-Resistant Isolate of Blastocystis spp. Is Susceptible to Nitric Oxide and Downregulates Intestinal Epithelial Inducible Nitric Oxide Synthase by a Novel Parasite Survival Mechanism

et al. 2011

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“…There are some reports indicating that DNA fragmentation cannot always be regarded as a hallmark for apoptosis, as certain cells display morphological and biochemical features of apoptosis without a typical ladder-like DNA fragmentation (Collins et al, 1992;Howell & Martz, 1987;Barbieri et al, 1992;Mesner et al, 1992;Falcieri et al, 1993;Vaux et al, 1994;Hirata et al, 1998). Ramos et al (2007) reported four bands smaller than 500 bp and Villalba et al (2007) found a more heterogeneous digestion pattern with a smear of degraded DNA containing faint ladder bands for E. histolytica trophozoites when induced to PCD by nitrosative stress and aminoglycosidic antibiotic G418 respectively. These observations are similar to ours for E. histolytica trophozoites exposed to H 2 O 2 .…”

Section: Discussionmentioning

confidence: 99%

“…But it is not established whether exposure to H 2 O 2 can bring about apoptosis-like death in E. histolytica trophozoites, although it is well established that H 2 O 2 can kill them (Ghadirian et al, 1986). Recent reports suggested that apoptosis-like death can be induced by the aminoglycosidic antibiotic G418 (Villalba et al, 2007) and nitric oxide species (Ramos et al, 2007) in E. histolytica trophozoites. In the present study we aimed to demonstrate H 2 O 2 -induced death of E. histolytica trophozoites as a model to study the death-associated phenotype and to identify possible biochemical pathways.…”

Section: Introductionmentioning

confidence: 99%

Hydrogen peroxide induces apoptosis-like death in Entamoeba histolytica trophozoites

et al. 2010

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Programmed cell death (PCD) is an essential process in the growth and development of multicellular organisms. However, accumulating evidence indicates that unicellular eukaryotes can also undergo PCD with apoptosis-like features. This study demonstrates that after exposure to 0.8 mM H 2 O 2 for 9 h Entamoeba histolytica presents morphological and biochemical evidence of apoptosis-like death. Morphological characteristics of apoptosis-like death including DNA fragmentation, increased vacuolization, nuclear condensation and cell rounding were observed for H 2 O 2 -exposed trophozoites with preservation of membrane integrity. Biochemical alteration in ion fluxes is also a key feature in PCD, and H 2 O 2 -exposed trophozoites showed overproduction of reactive oxygen species, increased cytosolic Ca 2+ and decreased intracellular pH.Phosphatidylserine was also found to be expressed in the outer leaflet of the plasma membrane of the H 2 O 2 -treated trophozoites. Pretreatment with the cysteine protease inhibitor E-64d, the extracellular and intracellular Ca 2+ chelators EGTA and BAPTA/AM, and the Ca 2+ influx inhibitor verapamil prior to H 2 O 2 exposure abolished DNA fragmentation. The oxidatively stressed trophozoites also showed an increased calpain activity, indicating involvement of Ca 2+ -dependent calpain-like cysteine proteases in PCD of E. histolytica. A homogeneous caspase assay showed no significant caspase activity, and administration of caspase 1 inhibitor also did not prevent the death phenotype for the oxidatively stressed trophozoites, indicating a caspaseindependent apoptosis-like death. Our observations clearly demonstrate that there is a distinct calpain-dependent but caspase-independent pathway for apoptosis-like death in oxidatively stressed E. histolytica trophozoites.

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Apoptosis in Acanthamoeba castellanii belonging to the T4 genotype

2017

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Here we describe features of apoptosis in unicellular Acanthamoeba castellanii belonging to the T4 genotype. When exposed to apoptosis-inducing compounds such as doxorubicin, A. castellanii trophozoites exhibited cell shrinkage and membrane blebbing as observed microscopically, DNA fragmentation using agarose gel electrophoresis, and phosphatidylserine (PS) externalization using annexin V immunostaining. Overall, these findings suggest the existence of apoptosis in A. castellanii possibly mediated by intrinsic apoptotic cascade. Further research in this field could provide avenues to selectively induce apoptosis in A. castellanii by triggering intrinsic apoptotic cascade.

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Entamoeba histolytica: Apoptosis induced in vitro by nitric oxide species

Cited by 50 publications

References 33 publications

A Metronidazole-Resistant Isolate of Blastocystis spp. Is Susceptible to Nitric Oxide and Downregulates Intestinal Epithelial Inducible Nitric Oxide Synthase by a Novel Parasite Survival Mechanism

A Metronidazole-Resistant Isolate of Blastocystis spp. Is Susceptible to Nitric Oxide and Downregulates Intestinal Epithelial Inducible Nitric Oxide Synthase by a Novel Parasite Survival Mechanism

Hydrogen peroxide induces apoptosis-like death in Entamoeba histolytica trophozoites

Apoptosis in Acanthamoeba castellanii belonging to the T4 genotype

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