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  • 1
    Publication Date: 2012-10-12
    Description: Myocardial cell death is initiated by excessive mitochondrial Ca(2+) entry causing Ca(2+) overload, mitochondrial permeability transition pore (mPTP) opening and dissipation of the mitochondrial inner membrane potential (DeltaPsim). However, the signalling pathways that control mitochondrial Ca(2+) entry through the inner membrane mitochondrial Ca(2+) uniporter (MCU) are not known. The multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is activated in ischaemia reperfusion, myocardial infarction and neurohumoral injury, common causes of myocardial death and heart failure; these findings suggest that CaMKII could couple disease stress to mitochondrial injury. Here we show that CaMKII promotes mPTP opening and myocardial death by increasing MCU current (I(MCU)). Mitochondrial-targeted CaMKII inhibitory protein or cyclosporin A, an mPTP antagonist with clinical efficacy in ischaemia reperfusion injury, equivalently prevent mPTP opening, DeltaPsim deterioration and diminish mitochondrial disruption and programmed cell death in response to ischaemia reperfusion injury. Mice with myocardial and mitochondrial-targeted CaMKII inhibition have reduced I(MCU) and are resistant to ischaemia reperfusion injury, myocardial infarction and neurohumoral injury, suggesting that pathological actions of CaMKII are substantially mediated by increasing I(MCU). Our findings identify CaMKII activity as a central mechanism for mitochondrial Ca(2+) entry in myocardial cell death, and indicate that mitochondrial-targeted CaMKII inhibition could prevent or reduce myocardial death and heart failure in response to common experimental forms of pathophysiological stress.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471377/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471377/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Joiner, Mei-Ling A -- Koval, Olha M -- Li, Jingdong -- He, B Julie -- Allamargot, Chantal -- Gao, Zhan -- Luczak, Elizabeth D -- Hall, Duane D -- Fink, Brian D -- Chen, Biyi -- Yang, Jinying -- Moore, Steven A -- Scholz, Thomas D -- Strack, Stefan -- Mohler, Peter J -- Sivitz, William I -- Song, Long-Sheng -- Anderson, Mark E -- R01 HL062494/HL/NHLBI NIH HHS/ -- R01 HL070250/HL/NHLBI NIH HHS/ -- R01 HL079031/HL/NHLBI NIH HHS/ -- R01 HL083422/HL/NHLBI NIH HHS/ -- R01 HL084583/HL/NHLBI NIH HHS/ -- R01 HL090905/HL/NHLBI NIH HHS/ -- R01 HL113001/HL/NHLBI NIH HHS/ -- R01 HL62494/HL/NHLBI NIH HHS/ -- R01 HL70250/HL/NHLBI NIH HHS/ -- R56 NS056244/NS/NINDS NIH HHS/ -- England -- Nature. 2012 Nov 8;491(7423):269-73. doi: 10.1038/nature11444. Epub 2012 Oct 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine and Cardiovascular Center, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA. mei-ling-joiner@uiowa.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23051746" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/drug effects ; Calcium/*metabolism/pharmacology ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/antagonists & ; inhibitors/chemistry/*metabolism ; Cyclosporine/pharmacology ; Female ; Heart/drug effects/physiopathology ; Heart Failure/drug therapy/prevention & control ; Membrane Potential, Mitochondrial/drug effects/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mitochondria, Heart/enzymology/*metabolism/*pathology ; Mitochondrial Membrane Transport Proteins/metabolism ; Myocardial Infarction/drug therapy/prevention & control ; Myocardium/*enzymology/metabolism/*pathology ; Reperfusion Injury/enzymology/metabolism/pathology/prevention & control ; Serine/metabolism ; *Stress, Physiological/drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2014-09-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Joiner, Mei-Ling A -- Koval, Olha M -- Li, Jingdong -- He, B Julie -- Allamargot, Chantal -- Gao, Zhan -- Luczak, Elizabeth D -- Hall, Duane D -- Fink, Brian D -- Chen, Biyi -- Yang, Jinying -- Moore, Steven A -- Scholz, Thomas D -- Strack, Stefan -- Mohler, Peter J -- Sivitz, William I -- Song, Long-Sheng -- Anderson, Mark E -- England -- Nature. 2014 Sep 25;513(7519):E3. doi: 10.1038/nature13627.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Internal Medicine and Cardiovascular Center, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA [2] Department of Molecular Physiology &Biophysics, Carver College of Medicine, University of Iowa, 51 Newton Road, Iowa City, Iowa 52242, USA (M.A.J.); The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio 43210, USA (J.L., P.J.M.); Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA (B.J.H.); Johns Hopkins University School of Medicine, 1830 East Monument Street, 9th Floor, Suite 9026, Baltimore, Maryland 21287, USA (E.D.L., M.E.A.). ; Department of Internal Medicine and Cardiovascular Center, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA. ; University of Iowa Central Microscopy Research Facility, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA. ; Iowa City Veterans Affairs Medical, Iowa City, Iowa 52246, USA. ; 1] Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA [2] Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA. ; Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA. ; Department of Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA. ; 1] Department of Internal Medicine and Cardiovascular Center, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA [2] Iowa City Veterans Affairs Medical, Iowa City, Iowa 52246, USA. ; 1] Department of Internal Medicine and Cardiovascular Center, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA [2] Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA [3] Department of Molecular Physiology &Biophysics, Carver College of Medicine, University of Iowa, 51 Newton Road, Iowa City, Iowa 52242, USA (M.A.J.); The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio 43210, USA (J.L., P.J.M.); Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA (B.J.H.); Johns Hopkins University School of Medicine, 1830 East Monument Street, 9th Floor, Suite 9026, Baltimore, Maryland 21287, USA (E.D.L., M.E.A.).〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25254481" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/*metabolism ; Female ; Mitochondria, Heart/*metabolism/*pathology ; Myocardium/*enzymology/*pathology ; *Stress, Physiological
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Comparative Biochemistry and Physiology -- Part A: Physiology 98 (1991), S. 383-391 
    ISSN: 0300-9629
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    The @International Journal Of Applied Radiation And Isotopes 34 (1983), S. 865-869 
    ISSN: 0020-708X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Physics
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford [u.a.] : International Union of Crystallography (IUCr)
    Acta crystallographica 50 (1994), S. 2017-2019 
    ISSN: 1600-5759
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford [u.a.] : International Union of Crystallography (IUCr)
    Acta crystallographica 53 (1997), S. 1145-1148 
    ISSN: 1600-5759
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Helgoland marine research 33 (1980), S. 153-163 
    ISSN: 1438-3888
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The marine flagellateDunaliella bioculata, which is easily cultivated under laboratory conditions, is a suitable organism for assessing the importance of the radioactive contamination by3H bound to organic molecules. We have studied the uptake of the following tritiated precursors: thymidine-methyl-3H, adenine-2-3H, uridine-5-3H, l-leucine-4-3H, glycine-2-3H, l-arginine-3.4-3H, 1-aspartic acid-2. 3-3H, 1-phenylalanine-2.3-3H, D-glucose-2-3H and D-glucose-6-3H. Under the experimental conditions (2000 lux; incubation time 30 min), all tritiated molecules are taken up byD. bioculata. Their intracellular concentration may reach that of the external medium. However, leucine and adenine accumulate in the algae: their respective concentrations are 10 and 100 times higher than in the culture medium. The molecular distribution of3H has been studied by various biochemical techniques and by sieve chromatography on sepharose 4B. It has been found that more l-leucine-4-3H is incorporated into acid and acetone soluble substances than into proteins. Adenine-2-3H is mainly incorporated into macromolecules of biological significance (RNA, DNA). CsCl gradient centrifugation has shown that the total DNA ofDunaliella is constituted by a major (ϖ=1.707 g/cm3) and by a minor (ϖ=1.693 g/cm3) component.
    Type of Medium: Electronic Resource
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  • 8
    Publication Date: 2011-06-03
    Print ISSN: 1350-9047
    Electronic ISSN: 1476-5403
    Topics: Biology , Medicine
    Published by Springer Nature
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  • 9
    Publication Date: 1980-03-01
    Print ISSN: 1438-387X
    Electronic ISSN: 1438-3888
    Topics: Biology
    Published by BioMed Central
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  • 10
    Publication Date: 1997-08-15
    Print ISSN: 0108-2701
    Electronic ISSN: 1600-5759
    Topics: Chemistry and Pharmacology , Geosciences , Physics
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