TY - JOUR
T1 - Differential Effect of Simulated Microgravity on the Cellular Uptake of Small Molecules
AU - Tepper-Shimshon, Odelia
AU - Tetro, Nino
AU - Hamed, Roa’a
AU - Erenburg, Natalia
AU - Merquiol, Emmanuelle
AU - Dey, Gourab
AU - Haim, Agam
AU - Dee, Tali
AU - Duvdevani, Noa
AU - Kevorkian, Talin
AU - Blum, Galia
AU - Yavin, Eylon
AU - Eyal, Sara
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/9
Y1 - 2024/9
N2 - The space environment can affect the function of all physiological systems, including the properties of cell membranes. Our goal in this study was to explore the effect of simulated microgravity (SMG) on the cellular uptake of small molecules based on reported microgravity-induced changes in membrane properties. SMG was applied to cultured cells using a random-positioning machine for up to three hours. We assessed the cellular accumulation of compounds representing substrates of uptake and efflux transporters, and of compounds not shown to be transported by membrane carriers. Exposure to SMG led to an increase of up to 60% (p < 0.01) in the cellular uptake of efflux transporter substrates, whereas a glucose transporter substrate showed a decrease of 20% (p < 0.05). The uptake of the cathepsin activity-based probe GB123 (MW, 1198 g/mol) was also enhanced (1.3-fold, p < 0.05). Cellular emission of molecules larger than ~3000 g/mol was reduced by up to 50% in SMG (p < 0.05). Our findings suggest that short-term exposure to SMG could differentially affect drug distribution across membranes. Longer exposure to microgravity, e.g., during spaceflight, may have distinct effects on the cellular uptake of small molecules.
AB - The space environment can affect the function of all physiological systems, including the properties of cell membranes. Our goal in this study was to explore the effect of simulated microgravity (SMG) on the cellular uptake of small molecules based on reported microgravity-induced changes in membrane properties. SMG was applied to cultured cells using a random-positioning machine for up to three hours. We assessed the cellular accumulation of compounds representing substrates of uptake and efflux transporters, and of compounds not shown to be transported by membrane carriers. Exposure to SMG led to an increase of up to 60% (p < 0.01) in the cellular uptake of efflux transporter substrates, whereas a glucose transporter substrate showed a decrease of 20% (p < 0.05). The uptake of the cathepsin activity-based probe GB123 (MW, 1198 g/mol) was also enhanced (1.3-fold, p < 0.05). Cellular emission of molecules larger than ~3000 g/mol was reduced by up to 50% in SMG (p < 0.05). Our findings suggest that short-term exposure to SMG could differentially affect drug distribution across membranes. Longer exposure to microgravity, e.g., during spaceflight, may have distinct effects on the cellular uptake of small molecules.
KW - BCRP
KW - breast cancer resistance protein
KW - GB123
KW - glucose transporters
KW - MDR1
KW - microgravity
KW - MRP1
KW - multidrug resistance–associated proteins
KW - P-glycoprotein
KW - pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=85205315135&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics16091211
DO - 10.3390/pharmaceutics16091211
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C2 - 39339247
AN - SCOPUS:85205315135
SN - 1999-4923
VL - 16
JO - Pharmaceutics
JF - Pharmaceutics
IS - 9
M1 - 1211
ER -