Inhibitory effect of serotonin derivatives on high glucose-induced adhesion and migration of monocytes on human aortic endothelial cells.
Previous reports have shown that safflower-seed extract and its major antioxidant constituents, serotonin hydroxycinnamic amides, attenuated atherosclerotic lesion formation in apoE-deficient mice, as well as inflammation and aortic stiffness in human subjects. In the present report, we examined a still unknown cell-based mechanism of serotonin derivatives against the development of atherosclerosis, focusing our attention on their action against the increase of adhesion molecules and the release of chemotactic factors on human aortic endothelial cells, phenomena that represent the key events in the early stages of atherosclerogenesis. Serotonin derivatives N-(p-coumaroyl)serotonin and N-feruloylserotonin exerted an inhibitory effect on short-term high glucose-induced up-regulation of mRNA and protein of adhesion and migration factors, and the consequent adhesion and migration of monocytes to endothelial cells; they inhibited the activation of transcription factors such as NF-kappaB, and the overproduction of the mitochondrial superoxide by acting as scavengers of the superoxide radical. In addition, serotonin derivative concentration inside the cells and inside the mitochondria was increased in a time-dependent manner. These results identify a mechanism of action of serotonin derivatives against endothelial damage at a cellular level, and underline their benefits against the disorders and complications related to reactive oxygen species.
Piga
Rosaria
R
Department of Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan. rosariapiga@tiscali.it
Naito
Yuji
Y
Kokura
Satoshi
S
Handa
Osamu
O
Yoshikawa
Toshikazu
T
D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D031187:Carthamus tinctorius; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D018920:Coculture Techniques; D003864:Depression, Chemical; D042783:Endothelial Cells / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012701:Serotonin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D020298:U937 Cells; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D048868:Adaptor Proteins, Signal Transducing; D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; C428449:MOAP1 protein, human; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; C512561:N-feruloylserotonin; D012701:Serotonin; C114774:N-(p-coumaroyl)serotonin; D005947:Glucose