title: Nutritional regulation of coupling factor 6, a novel vasoactive and proatherogenic peptide.
abstract: High sodium, high glucose, and obesity are important risk factors for age-related diseases such as cardiovascular disease (CVDs), stroke, and cancer. Coupling factor 6 (CF6) is released from vascular endothelial cells and functions as a circulating peptide that inhibits prostacyclin and nitric oxide generation by intracellular acidosis. High glucose elevates CF6 by activation of protein kinase C and p38 mitogen-activated protein kinase, whereas CF6 causes type 2 diabetes mellitus, resulting in a high glucose vicious cycle. Low glucose increases inhibitory factor peptide 1, an endogenous inhibitor of CF6. High salt intake increases CF6 through nuclear factor κB signaling, whereas CF6 induces salt-sensitive hypertension and salt-induced congestive heart failure. Oral administration of vitamin C cancels salt-induced increase in CF6, and estrogen replacement leads to the delayed onset of CF6-induced salt-sensitive hypertension and the rescue from cardiac systolic dysfunction. Because CF6 contributes to the onset of CVDs, nutritional regulation of CF6 will shed light on the understanding of preventive strategy and mechanisms for CVDs and a target for therapy.
authors.affiliation: Department of Nursing Science, Hirosaki University Graduate School of Health Science, Hirosaki, Japan. Electronic address: Osanait@hirosaki-u.ac.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Osanai
authors.affiliation: Department of Nursing Science, Hirosaki University Graduate School of Health Science, Hirosaki, Japan.
authors.forename: Kasumi
authors.initials: K
authors.lastname: Mikami
authors.affiliation: Department of Nursing Science, Hirosaki University Graduate School of Health Science, Hirosaki, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Kitajima
authors.affiliation: Department of Nursing Science, Hirosaki University Graduate School of Health Science, Hirosaki, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Urushizaka
authors.affiliation: Department of Nursing Science, Hirosaki University Graduate School of Health Science, Hirosaki, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Kawasaki
authors.affiliation: Department of Nursing Science, Hirosaki University Graduate School of Health Science, Hirosaki, Japan.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tomisawa
authors.affiliation: Department of Nursing Science, Hirosaki University Graduate School of Health Science, Hirosaki, Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Itaki
authors.affiliation: Department of Nursing Science, Hirosaki University Graduate School of Health Science, Hirosaki, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Noto
authors.affiliation: Daiichi Sankyo Co., Ltd., Biologics Technology Research Laboratories Group 1, Pharmaceutical Technology Division, Gunma, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Magota
authors.affiliation: Department of Cardiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Tomita
mesh_terms: D000284:Administration, Oral; D001205:Ascorbic Acid / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis; D042783:Endothelial Cells / Q000378:metabolism*; D011464:Epoprostenol / Q000037:antagonists & inhibitors / Q000378:metabolism; D006333:Heart Failure / Q000175:diagnosis / Q000209:etiology; D006801:Humans; D006973:Hypertension / Q000175:diagnosis; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D010086:Oxidative Phosphorylation Coupling Factors / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000009:adverse effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D010086:Oxidative Phosphorylation Coupling Factors; D017673:Sodium Chloride, Dietary; D009569:Nitric Oxide; D011464:Epoprostenol; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; C000628217:F(6) ATPase; D025261:Mitochondrial Proton-Translocating ATPases; D001205:Ascorbic Acid
keywords: ATP synthase; Cardiovascular disease; Coupling factor 6; Diabetes; Glucose; Heart failure; Hypertension; Inhibitory factor 1; Salt; Vitamin C