Development of cellular hypertrophy by 8-hydroxyeicosatetraenoic acid in the human ventricular cardiomyocyte, RL-14 cell line, is implicated by MAPK and NF-κB.
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, α-MHC, and β-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-κB 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-κB, 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-κB-dependent mechanism
Zaid H
ZH
Maayah
Ghada
G
Abdelhamid
Ayman O S
AO
El-Kadi
D000328:Adult; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000633:toxicity*; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats
D006893:Hydroxyeicosatetraenoic Acids; D016328:NF-kappa B; C047628:8-hydroxyeicosatetraenoic acid; D020928:Mitogen-Activated Protein Kinases