Abstract:
:Leptin is a 16 kDa product of the obesity gene secreted primarily by adipocytes. We recently identified cardiomyocytes as a target for the direct hypertrophic effects of leptin and suggested that leptin may be a biological link between obesity and cardiovascular pathologies. Activation of the renin-angiotensin and endothelin systems is associated with development of cardiovascular diseases and plasma renin levels are elevated in obese individuals. We therefore determined possible interaction between these factors in mediating hypertrophy in cultured neonatal rat ventricular myocytes. Treatment for 24 h with leptin (3.1 nM), angiotensin II (100 nM) or endothelin-1 (ET-1, 10 nM) significantly increased cell area by 37%, 36% and 35%, respectively and significantly increased gene expression of myosin light chain-2 and alpha-skeletal actin as well as leucine incorporation. The hypertrophic effects of all three agents were prevented by leptin and a leptin triple mutant receptor antagonist whereas the AT(1) receptor blocker (Sar1-lle(8))-Ang II or the ET(A) receptor blocker BQ123 was ineffective against leptin-induced hypertrophy. Both angiotensin II and ET-1 significantly increased leptin levels in the culture medium by fivefold. Moreover, both angiotensin II and ET-1 increased the gene expression of the short form (OBRa) by 180% and long form (OBRb) of leptin receptors by 200%, and this increase was abolished by both leptin receptor and leptin antibodies and leptin triple mutant. Although both angiotensin II and ET-1 increased phosphorylation of MAPK (p38, ERK1/2 and JNK) and NF-kappaB, the ability of leptin blockade to attenuate the hypertrophic responses was generally dissociated from these effects suggesting an alternate, yet to be identified cellular pathway mediating this role of leptin. Our studies therefore suggest a novel autocrine function for leptin in mediating the hypertrophic effects of both angiotensin II and ET-1 in cardiac myocytes.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Rajapurohitam V,Javadov S,Purdham DM,Kirshenbaum LA,Karmazyn Mdoi
10.1016/j.yjmcc.2006.05.001subject
Has Abstractpub_date
2006-08-01 00:00:00pages
265-74issue
2eissn
0022-2828issn
1095-8584pii
S0022-2828(06)00564-5journal_volume
41pub_type
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2010.10.019
更新日期:2011-01-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0696
更新日期:1998-07-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2012.06.019
更新日期:2012-09-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2010.12.003
更新日期:2011-10-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2020.07.004
更新日期:2020-09-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2009.10.013
更新日期:2010-05-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2017.12.006
更新日期:2018-01-01 00:00:00
abstract::Studies using chemically-induced models of diabetes have shown the diabetic myocardium to exhibit abnormalities in cellular ion transport, which may affect susceptibility to reperfusion-induced arrhythmias. We studied the incidence of reperfusion-induced ventricular tachycardia (VT) and fibrillation (VF) in isolated h...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(92)93195-p
更新日期:1992-04-01 00:00:00
abstract::Cardiac hypertrophy has been well-characterized at the level of transcription. During cardiac hypertrophy, genes normally expressed primarily during fetal heart development are re-expressed, and this fetal gene program is believed to be a critical component of the hypertrophic process. Recently, alternative splicing o...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2013.05.004
更新日期:2013-09-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2015.03.017
更新日期:2015-07-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1999.1026
更新日期:1999-10-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2009.09.018
更新日期:2010-03-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2012.03.002
更新日期:2012-06-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(88)80144-5
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2017.09.001
更新日期:2017-11-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2014.02.002
更新日期:2014-08-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(84)80716-6
更新日期:1984-01-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2001.1364
更新日期:2001-05-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2020.04.013
更新日期:2020-05-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(85)80087-0
更新日期:1985-01-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(88)80019-1
更新日期:1988-08-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(02)00312-7
更新日期:2003-02-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2016.08.009
更新日期:2016-10-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.yjmcc.2008.05.015
更新日期:2008-08-01 00:00:00
abstract::We have studied the effects of pressure and volume overload as well as of norepinephrine (NE) alone and in combination on the expression of the proto-oncogenes c-fos and c-myc in isolated perfused working rat hearts. Using specific cDNA clones, the mRNAs of c-fos and c-myc were measured by Northern blots and quantifie...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(08)80045-4
更新日期:1995-01-01 00:00:00