F-actin microfilament polymerized by jasplakinolide affects the expression of aquaporin-4 in astrocytic swelling after oxygen-glucose deprivation and reoxygenation

Abstract

This study was to determine whether Jasplakinolide (JSK), an actin microfilament polymerization, reduced the astrocytic swelling induced by oxygen-glucose deprivation and reoxygenation (OGD/Reox) and whether this effect could be mediated through the modulation of aquaporin-4 (AQP4) expression. Astrocytes were obtained from rat spinal cord. Cells were subjected to reoxygenation after 5 h OGD. JSK with different concentrations (20, 50, 100, 200 and 400 nM) was added to astrocytes for 12 h before and during OGD/Reox. Then the cell volume and AQP4 expression were analyzed. The results showed that astrocytic swelling occurred with cell volume increasing after OGD/Reox and the severity was significantly attenuated by JSK. A strong increase of AQP4 protein expression was observed after OGD/Reox, reaching a peak at 1.5 h into reoxygenation. The increase in levels of AQP4 protein was significantly reduced by treatment with JSK. In addition, confocal microscopy analysis showed that the F-actin microfilament polymerization by JSK accounted for AQP4 downregulation in the plasma membrane. This study demonstrated that JSK could attenuate astrocytes swelling caused by OGD/Reox, an ischemia and reperfusion-like injury, and part of its protective effects might be related to the reorganization the F-actin microfilament and inhibiting the abundance expression of AQP4 protein.