Calcium-induced apoptosis in cultured, primary corneal endothelial cells from monkey
FASEB JOURNAL(2018)
摘要
Apoptosis plays a key role in the loss of corneal endothelial cells (CEC). Losses can occur during corneal storage and after transplantation. Unlike the epithelium, CEC do not regenerate. CEC stretch to compensate for dead cells. This reduces cell density, allows influx of water, and promotes formation of opacities. Several studies confirm that staurosporine and mitomycin cause apoptosis in CEC. However, molecular mechanisms responsible for apoptosis in CEC have not been well studied. The purpose of the present study was to determine if CEC apoptosis is initiated by calcium uptake. To increase calcium levels, cultured primary CEC from monkey were treated with either A23187 (A23) or thapsigargin (TG). The ionophore A23 allows influx of Ca 2+ across cell membranes, while TG inhibits the outward directed Ca 2+ ‐ATPase pump in endoplasmic reticulum (ER). We found that both A23 and TG caused: increased cytosolic calcium levels, up‐regulation of ER stress markers BiP and CHOP, and positive staining for TUNEL. Apoptosis was further confirmed by positive immunostaining for activated caspase‐3. The known CEC maker/calcium binding protein S100 was decreased after A23 treatment but not after TG. (Further testing is needed as to why only A23 down‐regulates S100). We suggest that apoptosis in CEC occurs when elevated cytosolic calcium stresses the ER, the stressed ER release calcium, and the calcium flows into the mitochondrial matrix to trigger the apoptotic response. The unfolded protein response (UPR) may also contribute since Ca‐mediated ER stress is known to cause CEC degeneration. Support or Funding Information Dr. Shearer receives consulting fees from, and Drs. Azuma and Nakajima are employees of, Senju Pharmaceutical Co., Ltd. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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关键词
primary corneal endothelial cells,endothelial cells,calcium‐induced apoptosis
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