Abstract
15-Hydroxyeicosatetraenoic acid (15-HETE) is produced by the catalytic metabolism of arachidonic acid by the enzyme 15-lipoxygenase. It is produced during hypoxia, and participates in the remodeling of pulmonary artery smooth muscle (PASM). Previous research has revealed that sirtuin 1 (SIRT1) involved in apoptosis in various cells and tissues. Herein, we attempted to determine whether 15-HETE counteracts SIRT1-promoted cell death in murine PASM cells (PASMCs). To verify this theory, we investigated changes in SIRT1 concentration in response to the counteraction of cell death by 15-HETE. We used western blotting and a terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay, and investigated the survival, nuclear morphology, and mitochondrial potential of the cells. Our results revealed that 15-HETE promotes the transcription and translation of SIRT1. Moreover, 15-HETE increases viability and impaired mitochondrial depolarization, and promotes the expression of Bcl-2 and Bcl-xL in PASMCs without serum. The reactions mentioned above were eliminated by SIRT1 inhibitors (EX 527 and SIRT1 inhibitor IV). Our findings suggest that 15-HETE is crucial for the protection of PASMCs against cell death, and the SIRT...Continue Reading
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