Amelioration of Glucolipotoxicity-Induced Endoplasmic Reticulum Stress by a 'Chemical Chaperone' in Human THP-1 Monocytes
| Autor: | Mariawilliam Sneha Maria, Jayashree Balasubramanyam, Madhur Agrawal, Raji Rajesh Lenin, Viswanathan Mohan, Muthuswamy Balasubramanyam |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
lcsh:Internal medicine
Article Subject lcsh:Specialties of internal medicine Endocrinology Diabetes and Metabolism lcsh:Medicine Apoptosis Biology medicine.disease_cause Phenylbutyrate lcsh:Diseases of the endocrine glands. Clinical endocrinology Monocytes Cell Line chemistry.chemical_compound lcsh:RC581-951 medicine Humans lcsh:RC31-1245 Cells Cultured lcsh:RC648-665 Caspase 3 Endoplasmic reticulum Monocyte lcsh:R General Medicine Tunicamycin Endoplasmic Reticulum Stress Phenylbutyrates Cell biology Oxidative Stress medicine.anatomical_structure chemistry Unfolded protein response Chemical chaperone Reactive Oxygen Species Oxidative stress Research Article DNA Damage |
| Zdroj: | Experimental Diabetes Research, Vol 2012 (2012) Experimental Diabetes Research |
| ISSN: | 1687-5303 1687-5214 |
| Popis: | Chronic ER stress is emerging as a trigger that imbalances a number of systemic and arterial-wall factors and promote atherosclerosis. Macrophage apoptosis within advanced atherosclerotic lesions is also known to increase the risk of atherothrombotic disease. We hypothesize that glucolipotoxicity might mediate monocyte activation and apoptosis through ER stress. Therefore, the aims of this study are (a) to investigate whether glucolipotoxicity could impose ER stress and apoptosis in THP-1 human monocytes and (b) to investigate whether 4-Phenyl butyric acid (PBA), a chemical chaperone could resist the glucolipotoxicity-induced ER stress and apoptosis. Cells subjected to either glucolipotoxicity or tunicamycin exhibited increased ROS generation, gene and protein (PERK, GRP-78, IRE1α, and CHOP) expression of ER stress markers. In addition, these cells showed increased TRPC-6 channel expression and apoptosis as revealed by DNA damage and increased caspase-3 activity. While glucolipotoxicity/tunicamycin increased oxidative stress, ER stress, mRNA expression of TRPC-6, and programmed the THP-1 monocytes towards apoptosis, all these molecular perturbations were resisted by PBA. Since ER stress is one of the underlying causes of monocyte dysfunction in diabetes and atherosclerosis, our study emphasize that chemical chaperones such as PBA could alleviate ER stress and have potential to become novel therapeutics. |
| Databáze: | OpenAIRE |
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