| First Author | Dou G | Year | 2012 |
| Journal | Free Radic Biol Med | Volume | 53 |
| Issue | 5 | Pages | 1111-22 |
| PubMed ID | 22781655 | Mgi Jnum | J:188048 |
| Mgi Id | MGI:5439049 | Doi | 10.1016/j.freeradbiomed.2012.06.042 |
| Citation | Dou G, et al. (2012) Deficiency of alphaB crystallin augments ER stress-induced apoptosis by enhancing mitochondrial dysfunction. Free Radic Biol Med 53(5):1111-22 |
| abstractText | Endoplasmic reticulum (ER) stress is linked to several pathological conditions including age-related macular degeneration. Excessive ER stress initiates cell death cascades which are mediated, in part, through mitochondrial dysfunction. Here, we identify alphaB crystallin as an important regulator of ER stress-induced cell death. Retinal pigment epithelial (RPE) cells from alphaB crystallin (-/-) mice, and human RPE cells transfected with alphaB crystallin siRNA, are more vulnerable to ER stress induced by tunicamycin. ER stress-mediated cell death is associated with increased levels of reactive oxygen species, depletion of glutathione in mitochondria, decreased superoxide dismutase activity, increased release of cytochrome c, and activation of caspases 3 and 4. The ER stress signaling inhibitors, salubrinal and 4-(2-aminoethyl) benzenesulfonyl fluoride, decrease mitochondrial damage and reduce RPE apoptosis induced by ER stress. Prolonged ER stress decreases levels of alphaB crystallin, thus exacerbating mitochondrial dysfunction. Overexpression of alphaB crystallin protects RPE cells from ER stress-induced apoptosis by attenuating increases in Bax, CHOP, mitochondrial permeability transition, and cleaved caspase 3. Thus, these data collectively demonstrate that alphaB crystallin provides critical protection of mitochondrial function during ER stress-induced RPE apoptosis. |
