Identification of differentially expressed microRNAs during lipotoxic endoplasmic reticulum stress in RAW264.7 macrophages
Turkish Journal of Biochemistry
Turkish Biochemistry Society
206 - 215
Item Usage Stats
MetadataShow full item record
Objective: Increased fatty acids in the circulation and their accumulation in non-adipose tissues play a significant role in the development of obesity related metabolic and inflammatory disorders such as insulin resistance, diabetes and atherosclerosis. While fat tissue has the ability to store excess fatty acids, uptake of excess fatty acids to other tissues burdens intracellular metabolic organelles such as mitochondria and endoplasmic reticulum (ER), leading to stress response and lipotoxic cell death. Unfolded protein response (UPR) is a key adaptation of the ER to stress. It is still not completely clear how lipids engage the UPR and how UPR manages both the adaptive and destructive consequences under its control. Increasing evidence point to the importance of miRNA regulation of the UPR as well as UPR’s role in miRNA biogenesis. In order to understand how lipids engage the UPR, we set forth to identify microRNAs regulated by lipotoxic ER stress in macrophages. Methods: We stressed the mouse macrophage cell line (RAW 264.7) with a saturated fatty acid, 500μM palmitate, reflecting the levels found in the circulation of obese patients. We analyzed the microRNAome profiles of this cell line using QRT-PCR based miScript miRNA PCR array which contained all known mouse microRNAs in miRBase release16 and performed pathway analysis for potential targets. Results: 227 microRNAs showed altered expression levels; 43 microRNAs above 2 fold difference and 13 microRNAs 3-24 fold difference. Pathway analysis enriched the target mRNAs of these lipotoxic ER stress associated miRNAs. Conclusion: When exposed to high concentrations of saturated fatty acids that can induce ER stress, macrophages display a dynamic range of changes in their microRNAome profiles. Our findings reflect the consequences of lipotoxic stress on circulating monocytes and tissue-associated macrophages in obesity. Further studies are needed to deliniate which UPR arm is reponsible for the microRNA changes reported here.
KeywordsLipotoxic endoplasmic reticulum stress
Unfolded protein response
Saturated fatty acid
Agar gel electrophoresis
Endoplasmic reticulum stress
Reverse transcription polymerase chain reaction
Unfolded protein response
Published Version (Please cite this version)https://doi.org/10.1515/tjb-2016-0031
Showing items related by title, author, creator and subject.
TRIB2 confers resistance to anti-cancer therapy by activating the serine/threonine protein kinase AKT Hill, R.; Madureira, P. A.; Ferreira, B.; Baptista, I.; Machado, S.; Colaço, L.; Dos Santos, M.; Liu, N.; Dopazo, A.; Ugurel, S.; Adrienn, A.; Kiss-Toth, E.; Isbilen, M.; Gure, A. O.; Link, W. (Nature Publishing Group, 2017)Intrinsic and acquired resistance to chemotherapy is the fundamental reason for treatment failure for many cancer patients. The identification of molecular mechanisms involved in drug resistance or sensitization is imperative. ...
Jnk1 deficiency in hematopoietic cells suppresses macrophage apoptosis and increases atherosclerosis in low-density lipoprotein receptor null mice Babaev, V. R.; Yeung, M.; Erbay, E.; Ding, L.; Zhang, Y.; May, J. M.; Fazio, S.; Hotamisligil, G. S.; Linton, M. F. (Lippincott Williams and Wilkins, 2016)Objective - The c-Jun NH 2 -terminal kinases (JNK) are regulated by a wide variety of cellular stresses and have been implicated in apoptotic signaling. Macrophages express 2 JNK isoforms, JNK1 and JNK2, which may have ...
Protein folding, misfolding and aggregation: the importance of two-electron stabilizing interactions Cieplak, A. S. (Public Library of Science, 2017)Proteins associated with neurodegenerative diseases are highly pleiomorphic and may adopt an all-α-helical fold in one environment, assemble into all-β-sheet or collapse into a coil in another, and rapidly polymerize in ...