This review focused on potential regulatory mechanisms of Trichomonas vaginalis virulence properties, cytoadherence, cytotoxicity, phagocytosis, hemolysis, induction of apoptosis, and immune evasion ...in response to environmental factors of the human urogenital tract, iron, zinc, and polyamines. Understanding the multifactorial nature of trichomonal pathogenesis and its regulation may help to unravel the survival strategies of trichomonads and to implement prevention policies, opportune diagnosis, and alternative treatments for control of trichomoniasis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The protozoan parasite
is exposed to reactive oxygen and nitric oxide species that have the potential to damage its genome.
harbors enzymes involved in DNA repair pathways like Base and Nucleotide ...Excision Repair. The majority of DNA repairs pathways converge in their final step in which a DNA ligase seals the DNA nicks. In contrast to other eukaryotes, the genome of
encodes only one DNA ligase (EhDNAligI), suggesting that this ligase is involved in both DNA replication and DNA repair. Therefore, the aim of this work was to characterize EhDNAligI, its ligation fidelity and its ability to ligate opposite DNA mismatches and oxidative DNA lesions, and to study its expression changes and localization during and after recovery from UV and H
O
treatment. We found that EhDNAligI is a high-fidelity DNA ligase on canonical substrates and is able to discriminate erroneous base-pairing opposite DNA lesions. EhDNAligI expression decreases after DNA damage induced by UV and H
O
treatments, but it was upregulated during recovery time. Upon oxidative DNA damage, EhDNAligI relocates into the nucleus where it co-localizes with EhPCNA and the 8-oxoG adduct. The appearance and disappearance of 8-oxoG during and after both treatments suggest that DNA damaged was efficiently repaired because the mainly NER and BER components are expressed in this parasite and some of them were modulated after DNA insults. All these data disclose the relevance of EhDNAligI as a specialized and unique ligase in
that may be involved in DNA repair of the 8-oxoG lesions.
The recombinant TvCP4 prepro region (ppTvCP4r) acts as an exogenous inhibitor of cathepsin L-like CPs from Trichomonas vaginalis (Cárdenas-Guerra et al., 2015 1). Here, we present the dataset of the ...trichomonad ppTvCP4r inhibitory effect against the CP proteolytic activities from other microorganisms, such as Naegleria fowleri and Acanthamoeba castellanii free-living amoeba. The proteolytic activity inhibition of total crude extracts (TCEs) of N. fowleri and A. castellanii was determined and recorded using a fluorogenic substrate specific for cathepsin L CPs without or with a ppTvCP4r treatment at different concentrations and pH.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The recombinant ppTvCP4 (ppTvCP4r) protein, a specific inhibitor of the proteolytic activity and virulence properties of Trichomonas vaginalis, depending on cathepsin L-like cysteine proteinases ...(CPs) (http:dx.doi.org/ 10.1016/j.biocel.2014.12.0011, http:dx.doi.org/ 10.1016/j.micinf.2013.09.0022, http:dx.doi.org/ 10.1155/2015/9467873) was stable in the elution buffer up to two months at 4°C. However, it was prone to aggregate in PBS (functional assay buffer) 1. Therefore, before functional assays, the aggregation kinetic of refolded ppTvCP4r was determined after the exchange to PBS. Samples of purified and refolded ppTvCP4r (0.15mg/ml) in PBS were incubated for 0–24h at 4 and 25°C, spun down, measured the protein concentration in the supernatant and checked for the presence of aggregated protein in the pellet. The concentration of protein progressively decreased in the supernatant through time at both temperatures as the protein aggregated. Data in this article are related to the research paper 1.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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•Trichocystatin-3 (TC-3) of Trichomonas vaginalis is an atypical stefin-like endogenous cysteine proteinase (CP) inhibitor.•TC-3 is localized in the cytoplasm, large vesicles, Golgi ...complex, and at the plasma membrane.•TC-3 inhibits the proteolytic activity of cathepsin L-like CPs.•TC-3 specifically binds to TvCP3, a trichomonad cathepsin L-like CP.•TC-3 shows a protective effect over trichomonal cytotoxicity toward HeLa cell monolayers.
Trichomonas vaginalis is a flagellated protist responsible for human trichomoniasis. T. vaginalis has three genes encoding for endogenous cysteine proteinase (CP) inhibitors, known as trichocystatin-1 through trichocystatin-3 (TC-1, TC-2, and TC-3). These inhibitors belong to the cystatin family. In this study, we characterized trichocystatin-3 (TC-3), an endogenous cysteine proteinase (CP) inhibitor of T. vaginalis. TC-3 possesses a signal peptide in the N-terminus and two putative glycosylation sites (typical of family 2, cystatins) but lacks the PW motif and cysteine residues (typical of family 1, stefins). Native TC-3 was recognized as an ∼18 kDa protein band in a T. vaginalis protein extract. By confocal microscopy, endogenous TC-3 was found in the Golgi complex, cytoplasm, large vesicles, and the plasma membrane. These localizations are consistent with an in silico prediction. In addition, the purified recombinant protein (TC-3r) functions as an inhibitor of cathepsin L CPs, such as human liver cathepsin L and trichomonad CPs, present in a proteinase-resistant extract (PRE). Via a pull-down assay using TC-3r as bait and PRE, we identified several trichomonad CPs targeted by TC-3, primarily TvCP3. These CP-TC-3 interactions occur in vesicles, in the cytoplasm, and on the parasite surface. In addition, TC-3r showed a protective effect on HeLa cell monolayers by inhibiting trichomonad surface CPs involved in cellular damage. Our results show that the endogenous inhibitor TC-3 plays a key role in the regulation of endogenous CP proteolytic activity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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•Trichomonas vaginalis cathepsin D-like aspartic proteinase (Tv-CatD) belongs to the pepsin family A1 of clan AA.•Tv-CatD is up-regulated by glucose.•Tv-CatD has multiple ...localizations: in vesicles and lysosomes, the Golgi complex, endoplasmic reticulum, and nucleus.•Tv-CatD degrades human hemoglobin.
Trichomonas vaginalis genome encodes ∼440 proteases, six of which are aspartic proteases (APs). However, only one belongs to a clan AA (EC 3.4.23.5), family A1 (pepsin A), cathepsin D-like protease. This AP is encoded by an 1113-bp gene (tv-catd), which translates into a 370-aa residues zymogen of 40.7-kDa and a theoretical pI of 4.6, generating a ∼35 kDa active enzyme after maturation (Tv-CatD). The goal of this study was to identify and analyze the effect of glucose on the expression of Tv-CatD at the transcript and protein levels, subcellular localization, and proteolytic activity. The qRT-PCR assays showed a ∼2-fold increase in tv-catd mRNA under high-glucose (HG) conditions compared to glucose-restriction (GR) conditions. We amplified, cloned, and expressed the tv-catd gene, and purified the recombinant precursor enzyme (Tv-CatDr) to generate a polyclonal antibody (anti-Tv-CatDr). Western blot (WB) and immunolocalization assays showed that glucose increases the amount of Tv-CatD in different subcellular localizations and in in vitro secretions. Additionally, Tv-CatD proteolytic activity was detected in protease-resistant extracts (PREs) using a synthetic fluorogenic peptide specific for cathepsin D/E APs at different pHs and in the presence of AP inhibitors. In a two-dimensional (2-DE) WB analysis of a PRE from parasites grown under GR and HG conditions, an anti-Tv-CatDr antibody detected a 35-kDa protein spot at pI 5.0 identified as the mature Tv-CatD form by mass spectrometry that showed proteolytic activity in 2-DE zymograms copolymerized with hemoglobin under both glucose conditions. Thus, Tv-CatD could be involved in trichomonal hemolysis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The objective was to compare the prevalence of subclinical atherosclerosis and cardiovascular risk (CVR) reclassification using six CVR algorithms and a carotid ultrasound in psoriatic arthritis ...(PsA) patients and controls. The method was cross-sectional study. A total of 81 patients aged 40–75 years, who fulfilled the 2006 CASPAR criteria and 81 controls matched by age, gender, and comorbidities were recruited. CVR was evaluated according to six CVR algorithms, including Framingham Risk Score (FRS)-lipids, FRS-body mass index (BMI), Atherosclerotic Cardiovascular Disease (ASCVD) Algorithm, Systematic Coronary Risk Evaluation (SCORE), QRISK3, and Reynolds Risk Score (RRS). A carotid ultrasound was performed to identify the presence of carotid plaque (CP) defined as a carotid intima media thickness ≥ 1.2 mm or a focal narrowing of the surrounding lumen ≥ 0.5mm. Patients with presence of CP, classified in the low-moderate risk by the CVR algorithms, were reclassified to a higher risk category. CP was more prevalent in PsA patients (44.4% vs 24.7%,
p
= 0
.
008), as was subclinical atherosclerosis (51.9% vs 33.3%,
p
= 0
.
017). When comparing the CVR reclassification to a higher risk category, a difference was found in the six CVR algorithms. The reclassification was more prevalent in PsA patients: 30.8% vs 12.3%,
p
= 0
.
004 with FRS-lipids; 28.4% vs 9.9%,
p
= 0
.
003 with FRS-BMI; 40.7% vs 19.8%,
p
= 0
.
003 with SCORE; 30.9% vs 16.0%,
p
= 0.026 with ASCVD algorithm; 37.0% vs 19.8%,
p
= 0
.
015 with RRS; and 33.3% vs 16.0%,
p
= 0
.
011 with QRISK3. The CVR algorithms underestimate the actual CVR of PsA patients. A carotid ultrasound should be considered as part of the CVR evaluation of PsA patients.
Key points
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Subclinical atherosclerosis was more prevalent in psoriatic arthritis patients than controls
.
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Cardiovascular risk reclassification, through a carotid ultrasound, according to traditional cardiovascular risk algorithms was more common in psoriatic arthritis patients
.
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The cardiovascular risk algorithm that showed the lowest reclassification rate in psoriatic arthritis patients was the FRS-BMI
.
•
All cardiovascular risk algorithms underestimate the actual risk of psoriatic arthritis patients, preventing the initiation of an adequate cardiovascular treatment
.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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