Abstract:
:Lipocalin-2 (Lcn2; also termed neutrophil gelatinase-associated lipocalin (NGAL)) levels correlate positively with heart failure (HF) yet mechanisms via which Lcn2 contributes to the pathogenesis of HF remain unclear. In this study, we used coronary artery ligation surgery to induce ischemia in wild-type (wt) mice and this induced a significant increase in myocardial Lcn2. We then compared wt and Lcn2 knockout (KO) mice and observed that wt mice showed greater ischemia-induced caspase-3 activation and DNA damage measured by TUNEL than Lcn2KO mice. Analysis of autophagy by LC3 and p62 Western blotting, LC3 immunohistochemistry and transmission electron microscopy (TEM) indicated that Lcn2 KO mice had a greater ischemia-induced increase in autophagy. Lcn2KO were protected against ischemia-induced cardiac functional abnormalities measured by echocardiography. Upon treating a cardiomyocyte cell line (h9c2) with Lcn2 and examining AMPK and ULK1 phosphorylation, LC3 and p62 by Western blot as well as tandem fluorescent RFP/GFP-LC3 puncta by immunofluorescence, MagicRed assay for lysosomal cathepsin activity and TEM we demonstrated that Lcn2 suppressed autophagic flux. Lcn2 also exacerbated hypoxia-induced cytochromc c release from mitochondria and caspase-3 activation. We generated an autophagy-deficient H9c2 cell model by overexpressing dominant-negative Atg5 and found significantly increased apoptosis after Lcn2 treatment. In summary, our data indicate that Lcn2 can suppress the beneficial cardiac autophagic response to ischemia and that this contributes to enhanced ischemia-induced cell death and cardiac dysfunction. J. Cell. Physiol. 232: 2125-2134, 2017. © 2016 Wiley Periodicals, Inc.
journal_name
J Cell Physioljournal_title
Journal of cellular physiologyauthors
Sung HK,Chan YK,Han M,Jahng JWS,Song E,Danielson E,Berger T,Mak TW,Sweeney Gdoi
10.1002/jcp.25672subject
Has Abstractpub_date
2017-08-01 00:00:00pages
2125-2134issue
8eissn
0021-9541issn
1097-4652journal_volume
232pub_type
杂志文章abstract::A rat pheochromocytoma cell line (PC12 cells) was used as a model to investigate the role of calmodulin and its multiple mRNAs in NGF-induced neuronal differentiation. The effect of NGF on the degree of differentiation was assayed using a simple differentiation scoring system. Significant increases in the differentiat...
journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041490309
更新日期:1991-12-01 00:00:00
abstract::We evaluated the role of CCL20 (MIP-3alpha) chemokine in cells directly involved in the remodeling of bone tissue (osteoblasts and osteoclasts) and we confirmed its expression in the subchondral bone tissue of rheumatoid arthritis (RA) patients. The expression of CCL20 and of its receptor CCR6 was evaluated in osteobl...
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journal_title:Journal of cellular physiology
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journal_title:Journal of cellular physiology
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更新日期:1991-11-01 00:00:00
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journal_title:Journal of cellular physiology
pub_type: 杂志文章
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更新日期:1993-01-01 00:00:00
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journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.1041540112
更新日期:1993-01-01 00:00:00
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journal_title:Journal of cellular physiology
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journal_title:Journal of cellular physiology
pub_type: 杂志文章
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更新日期:1997-03-01 00:00:00
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更新日期:2001-10-01 00:00:00
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journal_title:Journal of cellular physiology
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doi:10.1002/jcp.26569
更新日期:2018-09-01 00:00:00
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journal_title:Journal of cellular physiology
pub_type: 杂志文章
doi:10.1002/jcp.27433
更新日期:2019-05-01 00:00:00
abstract::Lithium has been used or explored to treat psychiatric and neurodegenerative diseases that are frequently associated with an abnormal immune status. It is likely that lithium may work through modulation of immune responses in these patients. Because dendritic cells (DC) play a central role in regulating immune respons...
journal_title:Journal of cellular physiology
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更新日期:2011-02-01 00:00:00
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journal_title:Journal of cellular physiology
pub_type: 杂志文章
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journal_title:Journal of cellular physiology
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更新日期:1995-02-01 00:00:00
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journal_title:Journal of cellular physiology
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abstract::Suramin is an anti-cancer drug which induces the differentiation of the human colon cancer clone HT29-D4. Yet chronic suramin treatment of these cells eventually leads to a marked disturbance of the lysosomal system, which consists in an accumulation of hypertrophied autophagic vacuoles and the occurrence of lamellate...
journal_title:Journal of cellular physiology
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journal_title:Journal of cellular physiology
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更新日期:1995-08-01 00:00:00
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更新日期:2011-07-01 00:00:00