ACELL August 46/2
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چکیده
Nakaura, Hiroyuki, Sachio Morimoto, Fumi Yanaga, Masashi Nakata, Hirofumi Nishi, Tsutomu Imaizumi, and Iwao Ohtsuki. Functional changes in troponin T by a splice donor site mutation that causes hypertrophic cardiomyopathy. Am. J. Physiol. 277 (Cell Physiol. 46): C225–C232, 1999.—A splice donor site mutation in intron 15 of the cardiac troponin T (TnT) gene has been shown to cause familial hypertrophic cardiomyopathy (HCM). In this study, two truncated human cardiac TnTs expected to be produced by this mutation were expressed in Escherichia coli and partially (50–55%) exchanged into rabbit permeabilized cardiac muscle fibers. The fibers into which a short truncated TnT, which lacked the COOH-terminal 21 amino acids because of the replacement of 28 amino acids with 7 novel residues, had been exchanged generated a Ca21-activated maximum force that was slightly, but statistically significantly, lower than that generated by fibers into which wild-type TnT had been exchanged when troponin I (TnI) was phosphorylated by cAMP-dependent protein kinase. A long truncated TnT simply lacking the COOH-terminal 14 amino acids had no significant effect on the maximum force-generating capability in the fibers with either phosphorylated or dephosphorylated TnI. Both these two truncated TnTs conferred a lower cooperativity and a higher Ca21 sensitivity on the Ca21-activated force generation than did wild-type TnT, independent of the phosphorylation of TnI by cAMP-dependent protein kinase. The results demonstrate that the splice donor site mutation in the cardiac TnT gene impairs the regulatory function of the TnT molecule, leading to an increase in the Ca21 sensitivity, and a decrease in the cooperativity, of cardiac muscle contraction, which might be involved in the pathogenesis of HCM.
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ACELL August 46/2
JOHN M. PARK,1 ROSALYN M. ADAM,1 CRAIG A. PETERS,1 PAUL D. GUTHRIE,1 ZIJIE SUN,2 MICHAEL KLAGSBRUN,3 AND MICHAEL R. FREEMAN3 1Urologic Laboratory, Department of Urology, 3Laboratory for Surgical Research, Children’s Hospital, and Department of Surgery, Harvard Medical School, Boston, Massachusetts 02115; and 2Departments of Surgery and Genetics, Stanford University School of Medicine, Stanford,...
متن کاملACELL November 46/5
ESTHER TITOS,1 NAN CHIANG,2 CHARLES N. SERHAN,2 MARIO ROMANO,3 JOAN GAYA,4 GLORIA PUEYO,5 AND JOAN CLÀRIA1 1DNA Unit and 4Hormonal Laboratory, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Hospital Clı́nic and 5Quı́mica Farmacéutica Bayer (Consumer Care Division), Barcelona 08036, Spain; 2Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Periop...
متن کاملACELL October 46/4
NABENDU S. CHATTERJEE,1 CHANDIRA K. KUMAR,1 ALVARO ORTIZ,1 STANLEY A. RUBIN,2 AND HAMID M. SAID1 1Medical Research Service, Veterans Affairs Medical Center, Long Beach 90822, and Department of Medicine and Physiology/Biophysics, University of California School of Medicine, Irvine 92697; and 2Veterans Affairs West Los Angeles, Los Angeles 90073, and Department of Medicine, University of Californ...
متن کاملACELL August 46/2
Tonkonogi, M., and K. Sahlin. Actively phosphorylating mitochondria are more resistant to lactic acidosis than inactive mitochondria. Am. J. Physiol. 277 (Cell Physiol. 46): C288–C293, 1999.—Oxidative phosphorylation of isolated rat skeletal muscle mitochondria after exposure to lactic acidosis in either phosphorylating or nonphosphorylating states has been evaluated. Mitochondrial respiration ...
متن کاملACELL August 46/2
Golovina, Vera A. Cell proliferation is associated with enhanced capacitative Ca21 entry in human arterial myocytes. Am. J. Physiol. 277 (Cell Physiol. 46): C343–C349, 1999.—Depletion of Ca21 stores in the sarcoplasmic reticulum (SR) activates extracellular Ca21 influx via capacitative Ca21 entry (CCE). Here, CCE levels in proliferating and growth-arrested human pulmonary artery smooth muscle c...
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