Inflammasome-Induced Osmotic Pressure and the Mechanical Mechanisms Underlying Astrocytic Swelling and Membrane Blebbing in Pyroptosis

Cell swelling and membrane blebbing are characteristic of pyroptosis. In the present study, we explored the role of intracellular tension activity in the deformation of pyroptotic astrocytes. Protein nanoparticle-induced osmotic pressure (PN-OP) was found to be involved in cell swelling and membrane blebbing in pyroptotic astrocytes, and was associated closely with inflammasome production and cytoskeleton depolymerization. However, accumulation of protein nanoparticles seemed not to be absolutely required for pyroptotic permeabilization in response to cytoskeleton depolymerization. Gasdermin D activation was observed to be involved in modification of typical pyroptotic features through inflammasome-induced OP upregulation and calcium increment. Blockage of nonselective ion pores can inhibit permeabilization, but not inflammasome production and ion influx in pyroptotic astrocytes. The results suggested that the inflammasomes, as protein nanoparticles, are involved in PN-OP upregulation and control the typical features of pyroptotic astrocytes.

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

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.