Changes in the Surface Expression of Intercellular Adhesion Molecule 3, the Induction of Apoptosis, and the Inhibition of Cell-Cycle Progression of Human Multidrug-Resistant Jurkat/A4 Cells Exposed to a Random Positioning Machine.

Alisa Sokolovskaya,Edward Virus,Dmitry Kolesov,Ekaterina Korneeva,Danila Zaichenko,Aslan Kubatiev,Aleksey Moskovtsev

doi:10.3390/ijms21030855

Abstract

Experiments from flight- and ground-based model systems suggest that unexpected alterations of the human lymphoblastoid cell line Jurkat, as well as effects on cell growth, metabolism, and apoptosis, can occur in altered gravity conditions. Using a desktop random positioning machine (RPM), we investigated the effects of simulated microgravity on Jurkat cells and their multidrug-resistant subline, Jurkat/A4 cells. The viability of Jurkat/A4 cells decreased after simulated microgravity in contrast with the Jurkat cells. At the same time, the viability between the experimental Jurkat cells and control Jurkat cells was not significantly different. Of note, Jurkat cells appeared as less susceptible to apoptosis than their multidrug-resistant clone Jurkat/A4 cells, whereas cell-cycle analysis showed that the percentage of Jurkat/A4 cells in the S-phase was increased after 72 and 96 h of RPM-simulated microgravity relative to their static counterparts. The differences in Jurkat cells at all phases between static and simulated microgravity were not significant. The surface expression of the intercellular adhesion molecule 3 (ICAM-3)—also known as cluster of differentiation (CD)50—protein was changed for Jurkat/A4 cells following exposure to the RPM. Changes in cell morphology were observed in the Jurkat/A4 cells after 96 h of RPM-simulated microgravity. Thus, we concluded that Jurkat/A4 cells are more sensitive to RPM-simulated microgravity as compared with the parental Jurkat cell line. We also suggest that intercellular adhesion molecule 3 may be an important adhesion molecule involved in the induction of leukocyte apoptosis. The Jurkat/A4 cells with an acquired multidrug resistance phenotype could be a useful model for studying the effects of simulated microgravity and testing anticancer drugs.

Highlights

Space experiments are of great value for the study of various physiological characteristics of the human body; health problems; and, in particular, cancer [1,2,3]
We concluded that Jurkat/A4 cells are more sensitive to random positioning machine (RPM)-simulated microgravity as compared with the parental Jurkat cell line
We suggest that intercellular adhesion molecule 3 may be an important adhesion molecule involved in the induction of leukocyte apoptosis

Summary

Introduction

Space experiments are of great value for the study of various physiological characteristics of the human body; health problems; and, in particular, cancer [1,2,3]. After simulated-microgravity exposure, apoptosis has been observed in glial cells [7], endothelial cells [8], thyroid cancer cells [9], and Jurkat cells [5]. Both real and simulated microgravity induces early alterations of the cytoskeleton in thyroid cancer cells [10], endothelial cells [11], glial cells [12], and human breast cancer cells MCF-7 [13]. In a suspension cell culture, conditions similar to microgravity can be established using different equipment such as a rotating wall bioreactor, a clinostat, a random positioning machine (RPM), and even magnets (magnetic levitation) [14]

Methods

Results

Conclusion