| First Author | Noh MR | Year | 2015 |
| Journal | Biochim Biophys Acta | Volume | 1852 |
| Issue | 9 | Pages | 1895-901 |
| PubMed ID | 26071644 | Mgi Jnum | J:233924 |
| Mgi Id | MGI:5788381 | Doi | 10.1016/j.bbadis.2015.06.004 |
| Citation | Noh MR, et al. (2015) C/EBP homologous protein (CHOP) gene deficiency attenuates renal ischemia/reperfusion injury in mice. Biochim Biophys Acta 1852(9):1895-901 |
| abstractText | C/EBP homologous protein (CHOP), a transcription factor for the expression of apoptosis-related genes, plays an important role in endoplasmic reticulum (ER) stress-related organ diseases, including diseases of the kidney. Here, we investigated the role of CHOP in ischemia/reperfusion (I/R)-induced acute kidney injury using CHOP-knockout (CHOP(-/-)) and wild type (CHOP(+/+)) mice. Fifteen or thirty minutes of bilateral renal ischemia (I/R) insult resulted in necrotic and apoptotic tubular epithelial cell death, together with increases in plasma creatinine (PCr) and blood urea nitrogen (BUN) concentrations. After I/R, BiP/GRP78 and CHOP expressions in the kidney gradually increased over time. CHOP expression was greater in the outer medulla than that in the cortex and localized intensely in the nucleus. I/R caused apoptosis of tubular epithelial cells in both CHOP(-/-) and CHOP(+/+) mice. The number of apoptotic cells after I/R was lower in CHOP(-/-) mice than that in CHOP(+/+) mice. Consistent with the degree of apoptosis, I/R-induced kidney morphological and functional damages were milder in CHOP(-/-) than that in CHOP(+/+) mice. The cleavage of procaspase-3 and the induction of Bax protein after I/R were lower in CHOP(-/-) than that in CHOP(+/+) mice. In contrast, the expression levels of Bcl-2, Bcl-xL, cIAP2, Mcl-1, and XIAP were higher in CHOP(-/-) than that in CHOP(+/+) mice. These results indicate that I/R induces ER stress, leading to the activation of CHOP-associated apoptosis signals, resulting in renal functional and histological damages. |
