title: Alterations in sarcoplasmic reticulum calcium-storing proteins in pressure-overload cardiac hypertrophy.
abstract: The alterations of intracellular calcium (Ca2+) homeostasis may be responsible for the contractile defects in pressure-overload cardiac hypertrophy. The Ca(2+)-adenosinetriphosphatase (ATPase) protein level of the sarcoplasmic reticulum (SR) is reduced in the hypertrophied or failing heart. However, it is not known whether Ca(2+)-storing proteins, including calsequestrin and calreticulin, are also altered during cardiac hypertrophy. We quantified SR Ca(2+)-regulatory proteins using Western blot analysis in left ventricular (LV) muscle isolated from sham-operated control rats (n = 6) and rats with pressure overload 4 wk after abdominal aortic constriction (n = 7). The contractile function of isolated LV myocytes, assessed by the sarcomere motion measured with laser diffraction, was depressed in aortic-constricted rats. The SR Ca(2+)-ATPase protein level was decreased to 56 +/- 9% (SE) of the control value in hypertrophied myocardium (P < 0.01). The calsequestrin protein level was not altered, whereas calreticulin was increased by 120 +/- 3% of the control value in aortic-constricted rats (P < 0.05). The alterations in SR Ca(2+)-regulatory proteins were equally observed in hypertrophied hearts even when the results were normalized using the amounts of myosin heavy chain proteins in each sample. Immunohistochemical staining of calsequestrin in the control heart showed cross striations at the Z lines, whereas calreticulin was hardly observed within myocytes but was intense within interstitial fibroblasts. In the hypertrophied heart, calreticulin was observed at the perinuclear region within the myocyte cytoplasm. These data indicate that pressure-overload cardiac hypertrophy causes the alterations in SR Ca(2+)-storing proteins as well as in Ca(2+)-ATPase, which may contribute to the contractile dysfunction of the hypertrophied myocytes.
authors.affiliation: Research Institute of Angiocardiology and Cardiovascular Clinic, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Y
authors.initials: Y
authors.lastname: Ishibashi
authors.forename: K
authors.initials: K
authors.lastname: Imanaka-Yoshida
authors.forename: S
authors.initials: S
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
authors.forename: M
authors.initials: M
authors.lastname: Sugimachi
authors.forename: Y
authors.initials: Y
authors.lastname: Urabe
authors.forename: A
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006973:Hypertension / Q000150:complications*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
chemical_list: D011506:Proteins; D002118:Calcium