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Pinho 2022 Antioxidants (Basel)

From Bioblast
Publications in the MiPMap
Pinho N, Bombaça AC, Wiśniewski JR, Dias-Lopes G, Saboia-Vahia L, Cupolillo E, de Jesus JB, de Almeida RP, Padrón G, Menna-Barreto R, Cuervo P (2022) Nitric oxide resistance in Leishmania (Viannia) braziliensis involves regulation of glucose consumption, glutathione metabolism and abundance of pentose phosphate pathway enzymes. https://doi.org/10.3390/antiox11020277

» Antioxidants (Basel) 11:277. PMID: 35204161 Open Access

Pinho Nathalia,  Bombaca Ana Cristina,  Wisniewski Jacek R,  Dias-Lopes Geovane,  Saboia-Vahia Leonardo,  Cupolillo Elisa,  de Jesus Jose Batista,  de Almeida Roque P,  Padron Gabriel,  Menna-Barreto Rubem,  Cuervo Patricia (2022) Antioxidants (Basel)

Abstract: In American Tegumentary Leishmaniasis production of cytokines, reactive oxygen species and nitric oxide (NO) by host macrophages normally lead to parasite death. However, some Leishmania braziliensis strains exhibit natural NO resistance. NO-resistant strains cause more lesions and are frequently more resistant to antimonial treatment than NO-susceptible ones, suggesting that NO-resistant parasites are endowed with specific mechanisms of survival and persistence. To tests this, we analyzed the effect of pro- and antioxidant molecules on the infectivity in vitro of L. braziliensis strains exhibiting polar phenotypes of resistance or susceptibility to NO. In addition, we conducted a comprehensive quantitative mass spectrometry-based proteomics analysis of those parasites. NO-resistant parasites were more infective to peritoneal macrophages, even in the presence of high levels of reactive species. Principal component analysis of protein concentration values clearly differentiated NO-resistant from NO-susceptible parasites, suggesting that there are natural intrinsic differences at molecular level among those strains. Upon NO exposure, NO-resistant parasites rapidly modulated their proteome, increasing their total protein content and glutathione (GSH) metabolism. Furthermore, NO-resistant parasites showed increased glucose analogue uptake, and increased abundance of phosphotransferase and G6PDH after nitrosative challenge, which can contribute to NADPH pool maintenance and fuel the reducing conditions for the recovery of GSH upon NO exposure. Thus, increased glucose consumption and GSH-mediated redox capability may explain the natural resistance of L. braziliensis against NO. Keywords: American Tegumentary Leishmaniasis (ATL), FASP, Leishmania braziliensis, Glutathione metabolism, Glycolysis, Mass spectrometry, Nitric oxide resistance, Nitrosative stress, Quantitative proteomics, Reactive nitrogen species, Reactive oxygen species Bioblast editor: Plangger M


Labels: MiParea: Respiration  Pathology: Infectious 

Organism: Protists 

Preparation: Intact organism 


Pathway: ROX  HRR: Oxygraph-2k 

2022-12