title: Significance of serum Zn-α2-glycoprotein for the regulation of blood pressure.
abstract: Zn-α2-glycoprotein (ZAG) (molecular weight=41 kDa) is one component in the α2 fraction of human plasma, and is reported to be associated with several diseases, such as cancers and metabolic syndromes. ZAG is also considered to be an important modulator of lipid metabolism. However, little is known about the correlation of serum ZAG levels with indicators of metabolic syndrome. Serum ZAG concentrations analyzed by enzyme-linked immunoassay were positively correlated with systolic and diastolic blood pressure in 326 subjects (236 males and 90 females) aged 17-79 years who had an annual health examination. By luciferase reporter and electrophoretic mobility shift assays, the core promoter region to regulate the ZAG gene expression was found to exist between -110 and -101. The transcription factor Sp1 interacted with this region, and Sp1 knockdown experiments showed that Sp1 critically regulated ZAG expression. Furthermore, ZAG increased the active form of RhoA, which was determined by pull-down assay. Increased serum ZAG concentrations induced, at least partly, by Sp1 may cause an increase in vascular tone through the activation of RhoA and contribute to elevated blood pressure.
authors.affiliation: Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Souichi
authors.initials: S
authors.lastname: Kurita
authors.affiliation: Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Takeuchi
authors.affiliation: Department of Orthopedic Surgery, Nagoya City University, Nagoya, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Ueyama
authors.affiliation: Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Dimitar P
authors.initials: DP
authors.lastname: Zankov
authors.affiliation: Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Pang
authors.affiliation: Department of Orthopedic Surgery, Nagoya City University, Nagoya, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Otsuka
authors.affiliation: 1] Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Shiga, Japan [2] Department of Nutrition, Tenshi College, Hokkaido, Japan.
authors.forename: Iwao
authors.initials: I
authors.lastname: Ohkubo
authors.affiliation: 1] Department of Orthopedic Surgery, Nagoya City University, Nagoya, Japan [2] Department of Orthopedics, Nagoya City Rehabilitation Hospital, Aichi, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ogikubo
authors.affiliation: Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Ogita
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood; D008875:Middle Aged; D009129:Muscle Tonus / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D029589:Seminal Plasma Proteins / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000502:physiology; D055815:Young Adult; D000090203:Zn-Alpha-2-Glycoprotein; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D029589:Seminal Plasma Proteins; D016329:Sp1 Transcription Factor; D000090203:Zn-Alpha-2-Glycoprotein; C066737:RHOA protein, human; D020742:rhoA GTP-Binding Protein