Methylglyoxal-derived hemoglobin advanced glycation end products induce apoptosis and oxidative stress in human umbilical vein endothelial cells
- Authors
- Lee, Jae Hyuk; Samsuzzaman, M.; Park, Myoung Gyu; Park, Sung Jean; Kim, Sun Yeou
- Issue Date
- 30-Sep-2021
- Publisher
- ELSEVIER
- Keywords
- Apoptosis; Endothelial dysfunction; Hb-AGEs; Hemoglobin; Methylglyoxal; ROS
- Citation
- International Journal of Biological Macromolecules, v.187, pp.409 - 421
- Journal Title
- International Journal of Biological Macromolecules
- Volume
- 187
- Start Page
- 409
- End Page
- 421
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/82089
- DOI
- 10.1016/j.ijbiomac.2021.07.058
- ISSN
- 0141-8130
- Abstract
- The presence of excess glucose promotes hemoglobin glycation via the biochemical modification of hemoglobin by dicarbonyl products. However, the precise effects of Hb-AGEs in human umbilical vein endothelial cells (HUVECs) are not known to date. Therefore, we investigated the tentative effects of Hb-AGEs in HUVECs. Initially, we used the AGE formation assay to examine the selectivity of MGO toward various proteins. Among all proteins, MGO-Hb-AGEs formation was higher compared to the formation of other dicarbonyl-mediated AGEs. Our next data demonstrated that treatment with 0.5 mg/mL of Hb-AGEs-4w significantly reduced cell viability in HUVECs. Further, we evaluated the role of MGO in conformational and structural changes in Hb. The results showed that Hb demonstrated a highly altered conformation upon incubation with MGO. Moreover, Hb-AGEs-4w treatment strongly increased ROS production, and decreased mitochondrial membrane potential in HUVECs, and moderately reduced the expression of phosphorylated forms of p-38 and JNK. We observed that Hb-AGEs-4w treatment increased the number of apoptotic cells and the Bax/Bcl-2 ratio and cleaved the nuclear enzyme PARP in HUVECs. Finally, Hb-AGEs also inhibited migration and proliferation of HUVECs, thus be physiologically significant in endothelial dysfunction. Taken together, our data suggest that Hb-AGEs may play a critical role in inducing vascular endothelial cell damage. Therefore, this study may provide a plausible explanation for the potential Hb-AGEs in human endothelial cell dysfunction of diabetic patients. © 2021
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