The Mitochondrial Cardiolipin Remodeling Enzyme Lysocardiolipin Acyltransferase Is a Novel Target in Pulmonary Fibrosis
Identifieur interne : 001D58 ( Ncbi/Curation ); précédent : 001D57; suivant : 001D59The Mitochondrial Cardiolipin Remodeling Enzyme Lysocardiolipin Acyltransferase Is a Novel Target in Pulmonary Fibrosis
Auteurs : Long Shuang Huang ; Biji Mathew ; Haiquan Li ; Yutong Zhao ; Shwu-Fan Ma ; Imre Noth ; Sekhar P. Reddy ; Anantha Harijith ; Peter V. Usatyuk ; Evgeny V. Berdyshev ; Naftali Kaminski ; Tong Zhou ; Wei Zhang ; Yanmin Zhang ; Jalees Rehman ; Sainath R. Kotha ; Travis O. Gurney ; Narasimham L. Parinandi ; Yves A. Lussier ; Joe G. N. Garcia ; Viswanathan NatarajanSource :
- American Journal of Respiratory and Critical Care Medicine [ 1073-449X ] ; 2014.
Abstract
Url:
DOI: 10.1164/rccm.201310-1917OC
PubMed: 24779708
PubMed Central: 4098083
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The Mitochondrial Cardiolipin Remodeling Enzyme Lysocardiolipin Acyltransferase Is a Novel Target in Pulmonary Fibrosis</title>
<author><name sortKey="Huang, Long Shuang" sort="Huang, Long Shuang" uniqKey="Huang L" first="Long Shuang" last="Huang">Long Shuang Huang</name>
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<author><name sortKey="Mathew, Biji" sort="Mathew, Biji" uniqKey="Mathew B" first="Biji" last="Mathew">Biji Mathew</name>
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<author><name sortKey="Li, Haiquan" sort="Li, Haiquan" uniqKey="Li H" first="Haiquan" last="Li">Haiquan Li</name>
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<author><name sortKey="Zhao, Yutong" sort="Zhao, Yutong" uniqKey="Zhao Y" first="Yutong" last="Zhao">Yutong Zhao</name>
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<author><name sortKey="Ma, Shwu Fan" sort="Ma, Shwu Fan" uniqKey="Ma S" first="Shwu-Fan" last="Ma">Shwu-Fan Ma</name>
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<author><name sortKey="Reddy, Sekhar P" sort="Reddy, Sekhar P" uniqKey="Reddy S" first="Sekhar P." last="Reddy">Sekhar P. Reddy</name>
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<author><name sortKey="Harijith, Anantha" sort="Harijith, Anantha" uniqKey="Harijith A" first="Anantha" last="Harijith">Anantha Harijith</name>
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<author><name sortKey="Usatyuk, Peter V" sort="Usatyuk, Peter V" uniqKey="Usatyuk P" first="Peter V." last="Usatyuk">Peter V. Usatyuk</name>
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</affiliation>
<affiliation><nlm:aff id="aff2"></nlm:aff>
</affiliation>
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<author><name sortKey="Berdyshev, Evgeny V" sort="Berdyshev, Evgeny V" uniqKey="Berdyshev E" first="Evgeny V." last="Berdyshev">Evgeny V. Berdyshev</name>
<affiliation><nlm:aff id="aff3"></nlm:aff>
</affiliation>
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<author><name sortKey="Kaminski, Naftali" sort="Kaminski, Naftali" uniqKey="Kaminski N" first="Naftali" last="Kaminski">Naftali Kaminski</name>
<affiliation><nlm:aff id="aff6"></nlm:aff>
</affiliation>
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<author><name sortKey="Zhou, Tong" sort="Zhou, Tong" uniqKey="Zhou T" first="Tong" last="Zhou">Tong Zhou</name>
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<author><name sortKey="Zhang, Yanmin" sort="Zhang, Yanmin" uniqKey="Zhang Y" first="Yanmin" last="Zhang">Yanmin Zhang</name>
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</affiliation>
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<author><name sortKey="Rehman, Jalees" sort="Rehman, Jalees" uniqKey="Rehman J" first="Jalees" last="Rehman">Jalees Rehman</name>
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</affiliation>
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<author><name sortKey="Kotha, Sainath R" sort="Kotha, Sainath R" uniqKey="Kotha S" first="Sainath R." last="Kotha">Sainath R. Kotha</name>
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</affiliation>
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</affiliation>
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<author><name sortKey="Parinandi, Narasimham L" sort="Parinandi, Narasimham L" uniqKey="Parinandi N" first="Narasimham L." last="Parinandi">Narasimham L. Parinandi</name>
<affiliation><nlm:aff id="aff8"></nlm:aff>
</affiliation>
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<author><name sortKey="Lussier, Yves A" sort="Lussier, Yves A" uniqKey="Lussier Y" first="Yves A." last="Lussier">Yves A. Lussier</name>
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</affiliation>
<affiliation><nlm:aff id="aff5"></nlm:aff>
</affiliation>
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<author><name sortKey="Garcia, Joe G N" sort="Garcia, Joe G N" uniqKey="Garcia J" first="Joe G. N." last="Garcia">Joe G. N. Garcia</name>
<affiliation><nlm:aff id="aff2"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Natarajan, Viswanathan" sort="Natarajan, Viswanathan" uniqKey="Natarajan V" first="Viswanathan" last="Natarajan">Viswanathan Natarajan</name>
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</affiliation>
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<series><title level="j">American Journal of Respiratory and Critical Care Medicine</title>
<idno type="ISSN">1073-449X</idno>
<idno type="eISSN">1535-4970</idno>
<imprint><date when="2014">2014</date>
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<front><div type="abstract" xml:lang="en"><p><bold>Rationale:</bold>
Lysocardiolipin acyltransferase (LYCAT), a cardiolipin-remodeling enzyme regulating the 18:2 linoleic acid pattern of mammalian mitochondrial cardiolipin, is necessary for maintaining normal mitochondrial function and vascular development. We hypothesized that modulation of LYCAT expression in lung epithelium regulates development of pulmonary fibrosis.</p>
<p><bold>Objectives:</bold>
To define a role for LYCAT in human and murine models of pulmonary fibrosis.</p>
<p><bold>Methods:</bold>
We analyzed the correlation of LYCAT expression in peripheral blood mononuclear cells (PBMCs) with the outcomes of pulmonary functions and overall survival, and used the murine models to establish the role of LYCAT in fibrogenesis. We studied the LYCAT action on cardiolipin remodeling, mitochondrial reactive oxygen species generation, and apoptosis of alveolar epithelial cells under bleomycin challenge.</p>
<p><bold>Measurements and Main Results:</bold>
LYCAT expression was significantly altered in PBMCs and lung tissues from patients with idiopathic pulmonary fibrosis (IPF), which was confirmed in two preclinical murine models of IPF, bleomycin- and radiation-induced pulmonary fibrosis. <italic>LYCAT</italic>
mRNA expression in PBMCs directly and significantly correlated with carbon monoxide diffusion capacity, pulmonary function outcomes, and overall survival. In both bleomycin- and radiation-induced pulmonary fibrosis murine models, <italic>hLYCAT</italic>
overexpression reduced several indices of lung fibrosis, whereas down-regulation of native LYCAT expression by siRNA accentuated fibrogenesis. <italic>In vitro</italic>
studies demonstrated that LYCAT modulated bleomycin-induced cardiolipin remodeling, mitochondrial membrane potential, reactive oxygen species generation, and apoptosis of alveolar epithelial cells, potential mechanisms of LYCAT-mediated lung protection.</p>
<p><bold>Conclusions:</bold>
This study is the first to identify modulation of LYCAT expression in fibrotic lungs and offers a novel therapeutic approach for ameliorating lung inflammation and pulmonary fibrosis.</p>
</div>
</front>
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