Expression of V-1, a novel catecholamine biosynthesis regulatory protein, is enhanced by hypertension in atrial myocytes of Dahl salt-sensitive rats Tohru Yamakuni, a, * Michio Hashimoto, b Hiroyuki Sakagami, c Toshifumi Yamamoto, d Masumi Kobayashi, e,f Yoshimi Fujii, b Hideko Yamamoto, g Dileep Kumar Rohra, a Yusuke Hiwatashi, a Takao Honma, f Hisatake Kondo, c Osamu Shido, b and Yasushi Ohizumi a a Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai 980-8578, Japan b Department of Physiology, Shimane Medical University, Izumo, Shimane 693-8501, Japan c Department of Cell Biology, Division of Histology, Graduate School of Medicine, Tohoku University, Seiryo-machi 2-1, Sendai 980-8575, Japan d Laboratory of Molecular Recognition, Graduate School of Integrated Science, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027, Japan e Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan f Department of Applied Biochemistry, School of Engineering, Tokai University, 1117 Kitakaname, Hirasawa, Kanagawa 259-1292, Japan g Department of Molecular Psychopharmacology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-0057, Japan Received 2 October 2002 Abstract V-1 positively controls catecholamine synthetic gene transcription to promote catecholamine production in PC12D cells. In this study, immunohistochemical analysis revealed that in Wistar rats, V-1 immunoreactivity was localized not only in sympathetic axonsbutalsointhecytoplasmofcardiomyocytes,andthattheimmunoreactivityinatrialmyocyteswasmoreintensethanthatin ventricularmyocytes.WesternblotanalysisalsoshowedthatV-1expressionlevelintheatriumwashigherthanthatintheventricle ofWistarrathearts.WhenDahlsalt-sensitive(DS)ratswerefedan8%NaCldietaftertheageof6weeks,bloodpressurewasraised 230mmHgat18weeks.V-1expressionwasshowntobeincreasedintheatrialmyocytesoftheseDSrats,butnotinthesympathetic axons,whenassayedbyimmunohistochemistry.Theseresultssuggestthatinnormotensiverats,V-1ispreferentiallyexpressedinthe cytoplasm of cardiomyocytes in the atrium rather than in the ventricle. It is also suggested that V-1 expression is increased by hypertension in DS rat atrium. Ó 2002 Elsevier Science (USA). All rights reserved. Keywords: V-1; Catecholamine biosynthesis; Cardiomyocyte; Hypertension; Dahl salt-sensitive rat V-1 is a cytosolic protein that has been originally identified as a developmentally regulated protein during postnatal cerebellar morphogenesis, and consists of 117 amino acids which contain 2.5 tandem repeats of the cdc10/SWI6 motif, also known as the ankyrin repeat [1,2]. This motif has been demonstrated to be essential forprotein–proteininteractionsbetweenmembersofthe cdc10/SWI6 motif-containing protein superfamily and specific partner proteins [3–5]. Later it has been found that V-1 ubiquitously occurs in various types of CNS neurons with considerable differences in the expression level among different brain regions [6], and that this protein is expressed by a wide variety of cells, including adrenal chromaffin cells, sympathetic neurons of the peripheral nervous system [7], and ovary cells [8]. Re- cently we have established stable transfectants that overexpressV-1usingaratpheochromocytomacellline, PC12D, and it has been demonstrated that V-1 stim- Biochemical and Biophysical Research Communications 298 (2002) 793–797 www.academicpress.com BBRC * Corresponding author. Fax: +81-22-217-6850. E-mail address: yamakuni@mail.pharm.tohoku.ac.jp (T. Yamak- uni). 0006-291X/02/$ - see front matter Ó 2002 Elsevier Science (USA). All rights reserved. PII:S0006-291X(02)02529-9