Redox imbalance induces remodeling of glucose metabolism in Rhipicephalus microplus embryonic cell line

氧化还原失衡诱导微小扇头蜱胚胎细胞系葡萄糖代谢重塑

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作者:Bárbara Della Noce, Renato Martins da Silva, Marcelle Vianna de Carvalho Uhl, Satoru Konnai, Kazuhiko Ohashi, Christiano Calixto, Angélica Arcanjo, Leonardo Araujo de Abreu, Stephanie Serafim de Carvalho, Itabajara da Silva Vaz Jr, Carlos Logullo

Abstract

Carbohydrate metabolism not only functions in supplying cellular energy but also has an important role in maintaining physiological homeostasis and in preventing oxidative damage caused by reactive oxygen species. Previously, we showed that arthropod embryonic cell lines have high tolerance to H2O2 exposure. Here, we describe that Rhipicephalus microplus tick embryonic cell line (BME26) employs an adaptive glucose metabolism mechanism that confers tolerance to hydrogen peroxide at concentrations too high for other organisms. This adaptive mechanism sustained by glucose metabolism remodeling promotes cell survival and redox balance in BME26 cell line after millimolar H2O2 exposure. The present work shows that this tick cell line could tolerate high H2O2 concentrations by initiating a carbohydrate-related adaptive response. We demonstrate that gluconeogenesis was induced as a compensation strategy that involved, among other molecules, the metabolic enzymes NADP-ICDH, G6PDH, and PEPCK. We also found that this phenomenon was coupled to glycogen accumulation and glucose uptake, supporting the pentose phosphate pathway to sustain NADPH production and leading to cell survival and proliferation. Our findings suggest that the described response is not atypical, being also observed in cancer cells, which highlights the importance of this model to all proliferative cells. We propose that these results will be useful in generating basic biological information to support the development of new strategies for disease treatment and parasite control.

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