Simulated microgravity increases susceptibility of intestinal epithelial cells to acetaldehyde‐induced barrier dysfunction

Abstract

Previously, we showed that intestinal epithelial cells (IEC) exposed to simulated microgravity display lower transepithelial resistance (TER) and delayed localization of tight junction proteins indicating a barrier defect. Here, we investigated whether simulated microgravity increases susceptibility to epithelial barrier defects by the alcohol metabolite, acetaldehyde. HT‐29 IEC were cultured (i) on microcarrier beads for 18 days in a rotating wall vessel (RWV) to simulate microgravity, (ii) on beads without microgravity (static control), and (iii) in flasks (flask control). After removal of cells from beads or flasks and seeding on semi‐permeable supports for 11 and 14 days, RWV and control IECs were pre‐incubated with phosphate buffered saline (PBS) for 1 hour followed by 0.5% vapor phase acetaldehyde or PBS alone for 5 hours. TER, expressed as % change, was measured following PBS preincubation and again after 5hr treatment. Acetaldehyde caused a greater TER decrease in RWV cells (−13 ± 4.9%; n=6; p<0.05) vs. static (−3 ± 6.9%; n=6) and flask controls (−6 ± 5 %; n=6). PBS alone had no significant effect. Acetaldehyde also increased permeability to 4KD FITC‐dextran in RWV cells vs. controls. ZO‐1 and occludin proteins showed correlative decreases in expression. These data suggest that a simulated microgravity environment increases acetaldehyde‐induced barrier defects. Supported by NIH UH2 AA019708–01.