Development of cellular hypertrophy by 8-hydroxyeicosatetraenoic acid in the human ventricular cardiomyocyte, RL-14 cell line, is implicated by MAPK and NF-kappa B

作者：Maayah Zaid H; Abdelhamid Ghada; El Kadi Ayman O S^*

来源：Cell Biology and Toxicology, 2015, 31(4-5): 241-259.

DOI：10.1007/s10565-015-9308-7

• RL-14 cells
• Cytochrome P450
• 8-HETE
• NF-kappa B
• MAPKs

Recent studies have established the role of mid-chain hydroxyeicosatetraenoic acids (mid-chain HETEs) in the development of cardiovascular disease. Among these mid-chains, 8-HETE has been reported to have a proliferator and proinflammatory action. However, whether 8-HETE can induce cardiac hypertrophy has never been investigated before. Therefore, the overall objectives of the present study are to elucidate the potential hypertrophic effect of 8-HETE in the human ventricular cardiomyocytes, RL-14 cells, and to explore the mechanism(s) involved. Our results showed that 8-HETE induced cellular hypertrophy in RL-14 cells as evidenced by the induction of cardiac hypertrophy markers ANP, BNP, alpha-MHC, and beta-MHC in a concentration- and time-dependent manner as well as the increase in cell surface area. Mechanistically, 8-HETE was able to induce the NF-kappa B activity as well as it significantly induced the phosphorylation of ERK1/2. The induction of cellular hypertrophy was associated with a proportional increase in the formation of dihydroxyeicosatrienoic acids (DHETs) parallel to the increase of soluble epoxide hydrolase (sEH) enzyme activity. Blocking the induction of NF-kappa B, ERK1/2, and sEH signaling pathways significantly inhibited 8-HETE-induced cellular hypertrophy. Our study provides the first evidence that 8-HETE induces cellular hypertrophy in RL-14 cells through MAPK- and NF-kappa B-dependent mechanism.

• 出版日期2015-10