Redirecting

A two-fer. Drugs that depend on HNE for their mechanism of action: Rapamycin and MOTS-c This also nicely links obesity and heart disease, hypertrophy in this case, via HNE's effect on AMPK. “Reactive oxygen species (ROS) are elevated in the heart in response to hemodynamic and metabolic stress and promote hypertrophic signaling. ROS also mediate the formation of lipid peroxidation-derived aldehydes that may promote myocardial hypertrophy. One lipid peroxidation by-product, 4-hydroxy-trans-2-nonenal (HNE), is a reactive aldehyde that covalently modifies proteins thereby altering their function. HNE adducts directly inhibit the activity of LKB1, a serine/threonine kinase involved in regulating cellular growth in part through its interaction with the AMP-activated protein kinase (AMPK), but whether this drives myocardial growth is unclear. We tested the hypothesis that HNE promotes myocardial protein synthesis and if this effect is associated with impaired LKB1–AMPK signaling....” “The lipid peroxidation product 4-hydroxy-trans-2-nonenal causes protein synthesis in cardiac myocytes via activated mTORC1–p70S6K–RPS6 signaling...” “HNE-stimulated RPS6 phosphorylation was completely blocked using the mTOR inhibitor rapamycin.” “These data demonstrate that HNE causes protein synthesis and suggest it may directly inhibit AMPK to mediate downstream hypertrophic signaling via mTORC1–p70S6K–RPS6 in cardiac myocytes.” “The lipid peroxidation product 4-hydroxy-trans-2-nonenal causes protein synthesis in cardiac myocytes via activated mTORC1–p70S6K–RPS6 signaling.”