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Plasma membrane perforation by GSDME during apoptosis-driven secondary necrosis.

ABSTRACT: Secondary necrosis has long been perceived as an uncontrolled process resulting in total lysis of the apoptotic cell. Recently, it was shown that progression of apoptosis to secondary necrosis is regulated by Gasdermin E (GSDME), which requires activation by caspase-3. Although the contribution of GSDME in this context has been attributed to its pore-forming capacity, little is known about the kinetics and size characteristics of this. Here we report on the membrane permeabilizing features of GSDME by monitoring the influx and efflux of dextrans of different sizes into/from anti-Fas-treated L929sAhFas cells undergoing apoptosis-driven secondary necrosis. We found that GSDME accelerates cell lysis measured by SYTOX Blue staining but does not affect the exposure of phosphatidylserine on the plasma membrane. Furthermore, loss of GSDME expression clearly hampered the influx of fluorescently labeled dextrans while the efflux happened independently of the presence or absence of GSDME expression. Importantly, both in- and efflux of dextrans were dependent on their molecular weight. Altogether, our results demonstrate that GSDME regulates the passage of compounds together with other plasma membrane destabilizing subroutines.

SUBMITTER: De Schutter E

PROVIDER: S-EPMC8720079 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Plasma membrane perforation by GSDME during apoptosis-driven secondary necrosis.

De Schutter Elke E Ramon Jana J Pfeuty Benjamin B De Tender Caroline C Stremersch Stephan S Raemdonck Koen K de Beeck Ken Op KO Declercq Wim W Riquet Franck B FB Braeckmans Kevin K Vandenabeele Peter P

Cellular and molecular life sciences : CMLS 20211231 1

Secondary necrosis has long been perceived as an uncontrolled process resulting in total lysis of the apoptotic cell. Recently, it was shown that progression of apoptosis to secondary necrosis is regulated by Gasdermin E (GSDME), which requires activation by caspase-3. Although the contribution of GSDME in this context has been attributed to its pore-forming capacity, little is known about the kinetics and size characteristics of this. Here we report on the membrane permeabilizing features of GS ...[more]

PMID: 34971436

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Project description:Platelet-rich plasma (PRP) is a reliable and has low side-effect profile and has beneficial effects on wound healing. Its investigatory effects on wound-healing process were shown on various tissues. This study aims to investigate PRP's local application effects to perforated rat TM in terms of healing and histopatological outcomes. Twenty-two Wistar rats were used in the study. The rats' ears were examined with a pediatric endoscope (2.7 mm, 0°), and the TM posterior quadrant of their right ear was perforated with a 20-gauge needle. After this procedure, the rats were divided into two equal groups. A spongel with PRP was applied on the perforated TM in the first group, and spongel with standard saline solution was applied on the second group. Following the sacrifice, the middle air bullas were carefully dissected and removed for histopathological examination. Hematoxylin eosin (for fibroblasts, lymphocyte, collagen fibers) and immunohistochemical staining were done for epithelial growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR1), and vascular endothelial growth factor (VEGF) staining for histopathologic examinations. There was not a significant difference between the two groups for lymphocyte. There was a significant difference between control and study groups for collagen and EGFR (P < 0.05). Although the mean value of FGF- and VEGF-positive cells was higher in the study group than in the control group, the difference was not significant (P > 0.05). PRP is an effective autologous material for the healing process of acute TM perforations in a rat model, as demonstrated in the present study. We think that the use of PRP for acute TM perforations can have a positive effect on the healing process by increasing the level of growth factors, especially EGFR. In addition, an increase in collagen can also have a positive effect on healing.Supplementary informationThe online version contains supplementary material available at 10.1007/s12070-021-02912-2.

Dataset Information

Plasma membrane perforation by GSDME during apoptosis-driven secondary necrosis.

Publications

Plasma membrane perforation by GSDME during apoptosis-driven secondary necrosis.

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