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In hematophagous arthropods, however, these processes are not largely understood. Here, we describe that <jats:italic>Rhipicephalus microplus<\/jats:italic> ticks and embryonic cell line (BME26) employ an adaptive metabolic compensation mechanism that confers tolerance to hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) at concentrations too high for others organisms. Tick survival and reproduction are not affected by H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> exposure, while BME26 cells morphology was only mildly altered by the treatment. Furthermore, H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>-tolerant BME26 cells maintained their proliferative capacity unchanged. We evaluated several genes involved in gluconeogenesis, glycolysis, and pentose phosphate pathway, major pathways for carbohydrate catabolism and anabolism, describing a metabolic mechanism that explains such tolerance. Genetic and catalytic control of the genes and enzymes associated with these pathways are modulated by glucose uptake and energy resource availability. Transient increase in ROS levels, oxygen consumption, and ROS-scavenger enzymes, as well as decreased mitochondrial superoxide levels, were indicative of cell adaptation to high H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> exposure, and suggested a tolerance strategy developed by BME26 cells to cope with oxidative stress. Moreover, NADPH levels increased upon H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> challenge, and this phenomenon was sustained mainly by G6PDH activity. Interestingly, G6PDH knockdown in BME26 cells did not impair H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> tolerance, but generated an increase in NADP-ICDH transcription. In agreement with the hypothesis of a compensatory NADPH production in these cells, NADP-ICDH knockdown increased G6PDH relative transcript level. The present study unveils the first metabolic evidence of an adaptive mechanism to cope with high H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> exposure and maintain redox balance in ticks.<\/jats:p>","DOI":"10.1038\/s41598-019-41036-0","type":"journal-article","created":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T11:03:45Z","timestamp":1553079825000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Carbohydrate Metabolic Compensation Coupled to High Tolerance to Oxidative Stress in Ticks"],"prefix":"10.1038","volume":"9","author":[{"given":"B\u00e1rbara","family":"Della Noce","sequence":"first","affiliation":[]},{"given":"Marcelle Vianna de","family":"Carvalho Uhl","sequence":"additional","affiliation":[]},{"given":"Josias","family":"Machado","sequence":"additional","affiliation":[]},{"given":"Camila Fernanda","family":"Waltero","sequence":"additional","affiliation":[]},{"given":"Leonardo Araujo","family":"de Abreu","sequence":"additional","affiliation":[]},{"given":"Renato Martins","family":"da Silva","sequence":"additional","affiliation":[]},{"given":"Rodrigo Nunes","family":"da Fonseca","sequence":"additional","affiliation":[]},{"given":"Cintia Monteiro","family":"de Barros","sequence":"additional","affiliation":[]},{"given":"Gabriela","family":"Sabadin","sequence":"additional","affiliation":[]},{"given":"Satoru","family":"Konnai","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0309-9328","authenticated-orcid":false,"suffix":"Jr.","given":"Itabajara","family":"da Silva Vaz","sequence":"additional","affiliation":[]},{"given":"Kazuhiko","family":"Ohashi","sequence":"additional","affiliation":[]},{"given":"Carlos","family":"Logullo","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2019,3,18]]},"reference":[{"key":"41036_CR1","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1152\/physrev.1979.59.3.527","volume":"59","author":"B Chance","year":"1979","unstructured":"Chance, B., Sies, H. & Boveris, A. 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