Abstract
Reactive oxygen species (ROS) are natural byproducts of metabolism that have toxic effects well documented in mammals. In hematophagous arthropods, however, these processes are not largely understood. Here, we describe that Rhipicephalus microplus ticks and embryonic cell line (BME26) employ an adaptive metabolic compensation mechanism that confers tolerance to hydrogen peroxide (H2O2) at concentrations too high for others organisms. Tick survival and reproduction are not affected by H2O2 exposure, while BME26 cells morphology was only mildly altered by the treatment. Furthermore, H2O2-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 H2O2 exposure, and suggested a tolerance strategy developed by BME26 cells to cope with oxidative stress. Moreover, NADPH levels increased upon H2O2 challenge, and this phenomenon was sustained mainly by G6PDH activity. Interestingly, G6PDH knockdown in BME26 cells did not impair H2O2 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 H2O2 exposure and maintain redox balance in ticks.
Highlights
Arthropod cell lines were established as models to study several biological processes, including metabolism, signaling, vector-pathogen interactions, and oxidative stress[10,11,12,13,14]
In the interest of understanding how hematophagous arthropods cope with oxidative stress caused by the high amounts of heme ingested during blood feeding, several biochemical studies have been performed in organisms such as Rhodinus prolixus[16], Aedes aegypti[17] and Rhipicephalus microplus[18]
Treated ticks recovered from this injury (Fig. 1A) and were able to feed as successfully as control ticks (Fig. 1B), demonstrating their high H2O2 tolerance and ability to counteract H2O2-induced damage
Summary
Arthropod cell lines were established as models to study several biological processes, including metabolism, signaling, vector-pathogen interactions, and oxidative stress[10,11,12,13,14]. In the interest of understanding how hematophagous arthropods cope with oxidative stress caused by the high amounts of heme ingested during blood feeding, several biochemical studies have been performed in organisms such as Rhodinus prolixus[16], Aedes aegypti[17] and Rhipicephalus microplus[18]. We have used the BME26 tick cell line challenged with H2O2 to investigate a so-far undisclosed adaptive strategy that reduces ROS levels by regulating both transcription and activity of enzymes associated with aerobic and anaerobic carbohydrate metabolism and NADPH production. Such metabolic compensation makes ticks remarkably tolerant to oxidative stress
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