Additive effects of simulated microgravity and ionizing radiation in cell death, induction of ROS and expression of RAC2 in human bronchial epithelial cells

Shaobo Tan,Wentao Hu,Guangming Zhou,Hao Huang,Weiwei Pei

doi:10.1038/s41526-020-00123-7

Shaobo Tan, Wentao Hu + Show 3 more

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https://doi.org/10.1038/s41526-020-00123-7

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Journal: NPJ microgravity	Publication Date: Nov 5, 2020
Citations: 13	License type: open-access

Affiliation: Soochow University

Abstract

Radiation and microgravity are undoubtedly two major factors in space environment that pose a health threat to astronauts. However, the mechanistic study of their interactive biological effects is lacking. In this study, human lung bronchial epithelial Beas-2B cells were used to study the regulation of radiobiological effects by simulated microgravity (using a three-dimensional clinostat). It was found that simulated microgravity together with radiation induced drop of survival fraction, proliferation inhibition, apoptosis, and DNA double-strand break formation of Beas-2B cells additively. They also additively induced Ras-related C3 botulinum toxin substrate 2 (RAC2) upregulation, leading to increased NADPH oxidase activity and increased intracellular reactive oxygen species (ROS) yield. The findings indicated that simulated microgravity and ionizing radiation presented an additive effect on cell death of human bronchial epithelial cells, which was mediated by RAC2 to some extent. The study provides a new perspective for the better understanding of the compound biological effects of the space environmental factors.

Highlights

With the development of aerospace technology, astronauts spend more time in the space environment and the threats to the life and health of astronauts from space radiation become more serious[1,2]
We investigated the effects of both simulated microgravity (SMG) and ionizing radiation (IR) on the survival, proliferation, apoptosis, and DNA double-strand breaks damage of human bronchial epithelial Beas-2B cells, and revealed the combined biological effects of SMG and radiation are related to related C3 botulinum toxin substrate 2 (RAC2) expression, NADPH oxidase activity, and reactive oxygen species (ROS) yield
As for cells irradiated with the indicated doses of X-rays, IR inhibited the cell survival significantly at all the gradient doses from 1 Gy through 6 Gy (p < 0.05 at all dose points) (Fig. 1a), whereas the SMG and X-ray irradiation (SMG + IR) induced cell survival inhibition additively at all doses we tested as indicated by the similar survival curves (Fig. 1b)

Summary

Introduction

With the development of aerospace technology, astronauts spend more time in the space environment and the threats to the life and health of astronauts from space radiation become more serious[1,2]. The space environment is a multi-factor compounding field and the biological effects of space radiations are affected by a variety of space environmental factors, such as microgravity, weak magnetic fields, circadian rhythm changes, etc., which makes it difficult to demonstrate the biological effects of space radiations and increases the uncertainty of space radiation risk assessment[3,4,5,6]. As an inevitable space environmental factor, the effect of microgravity on the biological effects of radiation has received widespread attention[7]. Girardi et al.[8] studied the expression profiles of both miRNAs and mRNAs in human peripheral blood lymphocytes irradiated with γ-rays under simulated microgravity (SMG) conditions, and found that microgravity affects the radiation-induced DNA damage response pathway through bioinformatics analysis. Dang et al.[9] found that SMG aggravates human B-

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