The Impact of Long-Term Hypoxia on the Antioxidant Defense System in the Siberian Frog Rana amurensis

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Sergei V. Shekhovtsov^1,2,a*, Yana L. Vorontsova³, Irina A. Slepneva⁴, Dmitry N. Smirnov^5,6, Ekaterina E. Khrameeva⁵, Alexey Shatunov⁷, Tatiana V. Poluboyarova¹, Nina A. Bulakhova², Ekaterina N. Meshcheryakova², Daniil I. Berman², and Viktor V. Glupov³

¹Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia

²Institute of Biological Problems of the North, Far East Branch of the Russian Academy of Sciences, 630058 Magadan, Russia

³Institute of Systematics and Ecology of Animals, Siberian Branch of the Russian Academy of Sciences, 630091 Novosibirsk, Russia

⁴Voevodsky Institute of Chemical Kinetics and Combustion, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia

⁵Center for Molecular and Cellular Biology, Skolkovo Institute of Science and Technology, 121205 Moscow, Russia

⁶Department of Life Sciences, Ben-Gurion University of the Negev, 8410501 Beer Sheva, Israel

⁷Department of Clinical Neurosciences, University of Cambridge, CB2 0QQ Cambridge, United Kingdom

Received November 11, 2023; Revised December 16, 2023; Accepted December 29, 2023

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The Siberian frog Rana amurensis has a uniquely high tolerance to hypoxia among amphibians, as it is able to withstand several months underwater with almost no oxygen (0.2 mg/liter) vs. several days for other studied species. Since it was hypothesized that hypoxia actives the antioxidant defense system in hypoxia-tolerant animals, one would expect similar response in R. amurensis. Here, we studied the effect of hypoxia in the Siberian frog based on the transcriptomic data, activities of antioxidant enzyme, and content of low-molecular-weight antioxidants. Exposure to hypoxia upregulated expression of three relevant transcripts (catalase in the brain and two aldo-keto reductases in the liver). The activities of peroxidase in the blood and catalase in the liver were significantly increased, while the activity of glutathione S-transferase in the liver was reduced. The content of low-molecular-weight antioxidants (thiols and ascorbate) in the heart and liver was unaffected. In general, only a few components of the antioxidant defense system were affected by hypoxia, while most remained unchanged. Comparison to other hypoxia-tolerant species suggests species-specific adaptations to hypoxia-related ROS stress.

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KEY WORDS: hypoxia, transcriptomes, aldo-keto reductases, catalase, SOD, GSH

DOI: 10.1134/S0006297924030052

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