Dexmedetomidine Protects Human Renal Tubular Epithelial HK-2 Cells against Hypoxia/Reoxygenation Injury by Inactivating Endoplasmic Reticulum Stress Pathway

• Main Authors: Mingyu Zhai, Mingming Han, Xiang Huang, Fang Kang, Chengwei Yang, Juan Li
• Format: Article
• Language: English
• Published: Royan Institute (ACECR), Tehran 2021-09-01
• Series: Cell Journal
• Subjects: acute renal injury; dexmedetomidine; endoplasmic reticulum stress; human renal tubular epithelial
• Online Access: https://celljournal.org/journal/article/fulltext/dexmedetomidine-protects-human-renal-tubular-epithelial-hk-2-cells-against-hypoxiareoxygenation-injury-by-inactivating-endoplasmic-reticulum-stress-pathway.pdf
• ISSN: 2228-5806; 2228-5814

Objective: The study was aimed to investigate the effects and potential mechanisms of Dexmedetomidine (Dex) on hypoxia/reoxygenation (H/R) injury in human renal tubular epithelial HK-2 cells. Materials and Methods: In this experimental study, HK-2 cells were divided into four groups: control group, Dex group, H/R group, and Dex+H/R group. The cells in control group received no treatment, and cells in Dex group were only treated with 0.1 nmol/L Dex. The cells in H/R group and Dex+H/R group were all treated with H/R (hypoxia for 24 hours and normoxia for 4 hours), and only the cells in Dex+H/R group were pre-administrated with 0.1 nmol/L Dex. Following treatments at 37˚C for 28 hours, cell viability and apoptosis were measured by MTT assay and flow cytometry, respectively. Also, the expressions of hypoxia-inducible factor 1 (HIF-1α), glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), caspase-12 and cleaved caspase-3 were determined by western blot. Results: The cell viability was significant decreased in H/R group compared with control group (P<0.05), while was significantly increased in Dex+H/R group compared with that in H/R group (P<0.05). However, the change tendency of the cell apoptosis was opposite to that of cell viability. Compared with H/R group, the expression of HIF-1α was evidently up-regulated, while GRP78, CHOP, capase-12 and cleaved caspase-3 expressions were all obviously downregulated in Dex+H/R group (P<0.05). In addition, the concentrations of malondialdehyde (MDA) in H/R group and Dex+H/R group were 1.68 ± 0.22 nmol/mgprot and 0.85 ± 0.16 nmol/mgprot, respectively. The superoxide dismutase (SOD) activity was higher in Dex+H/R group (121 ± 11 U/L), which which was more than twice larger than that in H/R group (57 ± 10 U/L). Conclusion: Dex could promote cell viability and inhibit apoptosis through up-regulating HIF-1α, reducing endoplasmic reticulum (ER) stress and mediating oxidative stress, thus ameliorating the H/R injury.