Induction of the PERK-eIF2

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Abstract

Translation inhibition can activate two cell death pathways. The first pathway is activated by translational aberrations, the second by endoplasmic reticulum (ER) stress. In this work, the effect of ribosome-inactivating protein type II (RIP-II) viscumin on M1 macrophages derived from the THP-1 cell line was investigated. The number of modified ribosomes was evaluated by real-time PCR. Transcriptome analysis revealed that viscumin induces the ER stress activated by the PERK sensor.

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About the authors

O. E. Kolodeeva

Faculty of Biology and Biotechnology, HSE University

Author for correspondence.
Email: oekolodeeva@hse.ru
Russian Federation, Moscow

D. A. Averinskaya

Faculty of Biology and Biotechnology, HSE University

Email: oekolodeeva@hse.ru
Russian Federation, Moscow

Yu. А. Makarova

Faculty of Biology and Biotechnology, HSE University; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: oekolodeeva@hse.ru
Russian Federation, Moscow; Moscow

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2. Fig. 1. The viability curve of M1 macrophages during the treatment of cells with viscumin. The dots on the graph represent the average viability value for three biological repeats. The standard error of the mean was used as error bars. M1 macrophages obtained from the TNR-1 cell line were treated with the indicated viscumin concentrations for 6 hours, followed by washing and 24 hours incubation in a culture medium.

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3. Fig. 2. Assessment of EPR stress induction by RT-PCR. The change in the expression of log2(FC) in viscumin–treated M1 macrophages in the concentration range 0.1 - 100 nM was evaluated relative to control untreated M1 macrophages using the ΔΔCt method [20]. Statistical significance was assessed using the Student's t-test adjusted for multiplicity by the Benjamin-Hochberg method (** – p-adjusted < 0.005, * – p-adjusted < 0.05). ACTB and GAPDH were used as reference genes. The error bars show the standard error of the average for three biological repeats. Polarized M1 macrophages were treated with the indicated concentrations of viscumin for 6 hours, followed by incubation in a medium without viscumin for 24 hours.

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4. Fig. 3. Diagram of the UPR signaling pathway induced by EPR stress. Three UPR cascades activated by PARK, IRE1a and ATF6 sensors are shown.

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