Amelioration of glucolipotoxicity-induced endoplasmic reticulum stress by a chemical chaperone in human THP-1 monocytes

Raji Rajesh Lenin, Mariawilliam Sneha Maria, Madhur Agrawal, Jayashree Balasubramanyam, Viswanathan Mohan, Muthuswamy Balasubramanyam

Research output: Contribution to journalArticle

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Abstract

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, IRE1, 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.

Original languageEnglish (US)
Article number356487
JournalExperimental Diabetes Research
Volume2012
DOIs
StatePublished - May 21 2012

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Endoplasmic Reticulum Stress
Monocytes
Apoptosis
Butyric Acid
Tunicamycin
Atherosclerosis
Caspase 3
DNA Damage
Oxidative Stress
Macrophages
Messenger RNA
Proteins

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Music

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Amelioration of glucolipotoxicity-induced endoplasmic reticulum stress by a chemical chaperone in human THP-1 monocytes. / Rajesh Lenin, Raji; Maria, Mariawilliam Sneha; Agrawal, Madhur; Balasubramanyam, Jayashree; Mohan, Viswanathan; Balasubramanyam, Muthuswamy.

In: Experimental Diabetes Research, Vol. 2012, 356487, 21.05.2012.

Research output: Contribution to journalArticle

Rajesh Lenin, Raji ; Maria, Mariawilliam Sneha ; Agrawal, Madhur ; Balasubramanyam, Jayashree ; Mohan, Viswanathan ; Balasubramanyam, Muthuswamy. / Amelioration of glucolipotoxicity-induced endoplasmic reticulum stress by a chemical chaperone in human THP-1 monocytes. In: Experimental Diabetes Research. 2012 ; Vol. 2012.
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