Hypoxia worsens the impact of intracellular triglyceride accumulation promoted by electronegative low-density lipoprotein in cardiomyocytes by impairing perilipin 5 upregulation. (August 2015)

• Record Type: Journal Article
• Authors: Revuelta-López, Elena; Cal, Roi; Julve, Josep; Rull, Anna; Martínez-Bujidos, Maria; Perez-Cuellar, Montserrat; Ordoñez-Llanos, Jordi; Badimon, Lina; Sanchez-Quesada, Jose Luis; Llorente-Cortés, Vicenta
• Is Part Of: International journal of biochemistry & cell biology. Volume 65(2015:Aug.)
• Page Start: 257
• Page End: 267
• Publication Date: 2015-08
• Subjects: CE cholesteryl ester -- DHE dihydroethidium -- DiI 1, 1′-dioctadecyl-3, 3, 3′, 3′-tetramethylindocarbocyanine -- DM2 type 2 diabetes mellitus -- FA fatty acids -- FC free cholesterol -- GGE non-denaturing gradient gel electrophoresis -- LD lipid droplet -- LDL low-density lipoprotein -- LDL(−) electronegative LDL -- LDL(+) native LDL -- Lp-PLA2 lipoprotein-associated phospholipase A2 -- NEFA nonesterified fatty acids -- PC phosphatidylcholine -- PLC phospholipase C -- Plin5 perilipin 5 -- ROS reactive oxygen species; Cardiomyopathy -- Nonesterified fatty acids -- Electronegative LDL -- HL-1 cardiomyocytes -- Perilipin 5; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2015.06.014
• Languages: English
• ISSNs: 1357-2725

Abstract

Abstract: Plasma lipoproteins are a source of lipids for the heart, and the proportion of electronegative low density lipoprotein [LDL(−)] is elevated in cardiometabolic diseases. Perilipin 5 (Plin5) is a crucial protein for lipid droplet management in the heart. Our aim was to assess the effect of LDL(−) on intracellular lipid content and Plin5 levels in cardiomyocytes and to determine whether these effects were influenced by hypoxia. HL-1 cardiomyocytes were exposed to native LDL [LDL(+)], LDL(−), and LDL(+) enriched in non-esterified fatty acids (NEFA) by phospholipase A2 (PLA2 )-mediated lipolysis [PLA2 -LDL(+)] or by NEFA loading [NEFA-LDL(+)] under normoxia or hypoxia. LDL(−), PLA2 -LDL(+) and NEFA-LDL(+) raised the intracellular NEFA and triglyceride (TG) content of normoxic cardiomyocytes. Plin5 was moderately upregulated by LDL(+) but more highly upregulated by LDL(−), PLA2 -LDL(+) and NEFA-LDL(+) in normoxic cardiomyocytes. Hypoxia enhanced the effect of LDL(−), PLA2 -LDL(+) and NEFA-LDL(+) on intracellular TG and NEFA concentrations but, in contrast, counteracted the upregulatory effect of these LDLs on Plin5. Fluorescence microscopy experiments showed that hypoxic cardiomyocytes exposed to LDL(−), PLA2 -LDL(+) and NEFA-LDL(+) have an increased production of reactive oxygen species (ROS). By treating hypoxic cardiomyocytes with WY-14643 (PPARα agonist), Plin5 remained high. In this situation, LDL(−) failed to enhance intracellular NEFA concentration and ROS production. In conclusion, these results show that Plin5 deficiency in hypoxic cardiomyocytes exposed to LDL(−) dramatically increases the levels of unpacked NEFA and ROS.