Methylglyoxal-derived hemoglobin advanced glycation end products induce apoptosis and oxidative stress in human umbilical vein endothelial cells
| Autor: | Md. Samsuzzaman, Sung Jean Park, Jae Hyuk Lee, Myoung Gyu Park, Sun Yeou Kim |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Glycation End Products
Advanced Apoptosis medicine.disease_cause Biochemistry p38 Mitogen-Activated Protein Kinases Umbilical vein chemistry.chemical_compound Hemoglobins Structural Biology Glycation Cell Movement medicine Human Umbilical Vein Endothelial Cells Humans Viability assay Endothelial dysfunction Phosphorylation Molecular Biology Cells Cultured Cell Proliferation Membrane Potential Mitochondrial Methylglyoxal JNK Mitogen-Activated Protein Kinases General Medicine medicine.disease Pyruvaldehyde Cell biology Endothelial stem cell Oxidative Stress chemistry Apoptosis Regulatory Proteins Reactive Oxygen Species Oxidative stress Signal Transduction |
| Zdroj: | International journal of biological macromolecules. 187 |
| ISSN: | 1879-0003 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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