Abstract:
:The mitochondrial enzyme monoamine oxidase (MAO), its isoform MAO-A, plays a major role in reactive oxygen species-dependent cardiomyocyte apoptosis and postischemic cardiac damage. In the current study, we investigated whether sphingolipid metabolism can account for mediating MAO-A- and reactive oxygen species-dependent cardiomyocyte apoptosis. In H9c2 cardiomyoblasts, MAO-A-dependent reactive oxygen species generation led to mitochondria-mediated apoptosis, along with sphingosine kinase-1 (SphK1) inhibition. These phenomena were associated with generation of proapoptotic ceramide and decrease in prosurvival sphingosine 1-phosphate. These events were mimicked by inhibition of SphK1 with either pharmacological inhibitor or small interfering RNA, as well as by extracellular addition of C(2)-ceramide or H(2)O(2). In contrast, enforced expression of SphK1 protected H9c2 cells from serotonin- or H(2)O(2)-induced apoptosis. Analysis of cardiac tissues from wild-type mice subjected to ischemia/reperfusion revealed significant upregulation of ceramide and inhibition of SphK1. It is noteworthy that SphK1 inhibition, ceramide accumulation, and concomitantly infarct size and cardiomyocyte apoptosis were significantly decreased in MAO-A-deficient animals. In conclusion, we show for the first time that the upregulation of ceramide/sphingosine 1-phosphate ratio is a critical event in MAO-A-mediated cardiac cell apoptosis. In addition, we provide the first evidence linking generation of reactive oxygen species with SphK1 inhibition. Finally, we propose sphingolipid metabolites as key mediators of postischemic/reperfusion cardiac injury.
journal_name
Circ Resjournal_title
Circulation researchauthors
Pchejetski D,Kunduzova O,Dayon A,Calise D,Seguelas MH,Leducq N,Seif I,Parini A,Cuvillier Odoi
10.1161/01.RES.0000253900.66640.34subject
Has Abstractpub_date
2007-01-05 00:00:00pages
41-9issue
1eissn
0009-7330issn
1524-4571pii
01.RES.0000253900.66640.34journal_volume
100pub_type
杂志文章abstract::Genetically hypertensive (GH) rats of the New Zealand strain and normotensive (N) rats were sympathectomized from birth with 6-hydroxydopamine (100 mg/kg,s.c, on alternate days, seven treatments). In adult treated rats from each strain (GHTr and NTr), blood pressure was lower than normal. Functional tests and electron...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.43.2.293
更新日期:1978-08-01 00:00:00
abstract::Net cellular L-lactate efflux associated with accelerated anaerobic glycolysis has been implicated as a potential cause of the marked cellular K+ loss contributing to lethal cardiac arrhythmias in ischemic heart and to impaired function of fatigued skeletal muscle. To examine the mechanisms of transsarcolemmal L-lacta...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.74.5.829
更新日期:1994-05-01 00:00:00
abstract::Inflammation is a condition that underscores many cardiovascular pathologies including endothelial dysfunction, but no link is yet established between the vascular pathology of the metabolic syndrome with a particular inflammatory cytokine. We hypothesized that impairments in coronary endothelial function in the obese...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000229685.37402.80
更新日期:2006-07-07 00:00:00
abstract::Increased levels of C-peptide, a cleavage product of proinsulin, circulate in patients with insulin resistance and early type 2 diabetes mellitus. Recent data suggest a potential causal role of C-peptide in atherogenesis by promoting monocyte and T-lymphocyte recruitment into the vessel wall. The present study examine...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000251231.16993.88
更新日期:2006-11-24 00:00:00
abstract::The sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) plays a critical role in the contractile performance of cardiac and slow-twitch skeletal muscle by restoring cytosolic calcium to low resting levels during the contractile cycle. We have previously shown that SERCA2 expression in the heart is altered by a number of pat...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.73.4.622
更新日期:1993-10-01 00:00:00
abstract::Smaller Ca2+ transients and systolic dysfunction in heart failure (HF) can be largely explained by reduced total sarcoplasmic reticulum (SR) Ca2+ content ([Ca]SRT). However, it is unknown whether low [Ca]SRT is manifest as reduced: (1) intra-SR free [Ca2+] ([Ca2+]SR), (2) intra-SR Ca2+ buffering, or (3) SR volume (as ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.152140
更新日期:2007-10-12 00:00:00
abstract::Extracellular ATP plays an important role in the regulation of prostacyclin and nitric oxide release from vascular endothelial cells. These cellular responses to ATP are generally attributed to the stimulation of the P2y subtype of P2 purinergic receptors. However, it has recently been suggested that two types of ATP ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.72.3.504
更新日期:1993-03-01 00:00:00
abstract::Changes in cardiac filling pressure (central venous pressure) were measured following carotid occlusion and infusions of catecholamines in awake dogs while cardiac output was held constant. After carotid occlusion in dogs with vagi blocked, central venous pressure increased about 0.8 mm Hg (an estimated decrease in va...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.55.4.440
更新日期:1984-10-01 00:00:00
abstract::We studied product inhibition of the actin-activated ATPase of myosin subfragment-1 (S-1) from the three types of muscle tissue: skeletal, cardiac, and smooth. Increasing levels of [MgADP] in the 0-1-mM range caused significant inhibition of the actin-activated MgATPase activity of cardiac and gizzard but not skeletal...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.5.1067
更新日期:1992-11-01 00:00:00
abstract:RATIONALE:Protein kinase (PK)C-induced phosphorylation of cardiac troponin (cTn)I has been shown to regulate cardiac contraction. OBJECTIVE:Characterize functional effects of increased PKC-induced cTnI phosphorylation and identify underlying mechanisms using a transgenic mouse model (cTnI(PKC-P)) expressing mutant cTn...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.205427
更新日期:2009-12-04 00:00:00
abstract::Atherosclerotic lesion development seems to be inflammatory in nature and involves the recruitment of monocytes to the vessel wall. In this study, we investigated the role of vascular cell adhesion molecule-1 (VCAM-1) and fibronectin (FN) connecting segment-1 containing the amino acid sequence ILDV as functional ligan...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.2.153
更新日期:2000-07-21 00:00:00
abstract::In this review current hypotheses for the regulation of filtration rate and the subsequent reabsorption of that filtrate by the proximal tubule are discussed. In the rat the filtration rate is highly plasma flow dependent because of the phenomenon of filtration equilibrium. On the other hand, in man and dog filtration...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.res.36.6.107
更新日期:1975-06-01 00:00:00
abstract::After cervical aortic nerve section, mean arterial pressure in the unanesthetized dog increased by an average of 7.4 mm Hg. Following a more extensive denervation of aortic arch receptors by section of intrathoracic vagal branches, arterial pressure increased by 16.7 mm Hg. The above changes were seen in the stable st...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.45.1.26
更新日期:1979-07-01 00:00:00
abstract::Transforming growth factor (TGF)-beta(1) is a potent stimulator of intimal growth. We showed previously that TGF-beta(1) stimulates intimal growth through early upregulation of plasminogen activator inhibitor-1 (PAI-1) and, subsequently, PAI-1-dependent increases in cell migration and matrix accumulation. We also show...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000266970.34017.8d
更新日期:2007-05-11 00:00:00
abstract::The rate of renin secretion from renal juxtaglomerular (JG) cells is the major determinant of the activity of the renin-angiotensin system. However, the mechanisms involved in the excretion and turnover of secretory granules in the JG cells remain obscure. Therefore, in the present study, the whole-cell patch-clamp te...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.84.8.929
更新日期:1999-04-30 00:00:00
abstract:RATIONALE:Lipid-free apolipoprotein (apo) A-I and discoidal reconstituted high-density lipoproteins (rHDL) containing apoA-I, (A-I)rHDL, inhibit vascular inflammation by increasing 3β-hydroxysteroid-Δ24 reductase (DHCR24) expression. OBJECTIVE:To determine whether the lipid-free apoA-I-mediated and (A-I)rHDL-mediated ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.300104
更新日期:2013-01-18 00:00:00
abstract::The microelectrode technique of intracellular constant current application and intracellular transmembrane voltage recording was used to study the effects of procaine amide (PA) on cardiac excitability. We measured the effect of PA in a concentration equivalent to clinically effective antiarrhythmic plasma levels (5 m...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.38.2.115
更新日期:1976-02-01 00:00:00
abstract::Tyrosine kinase cascades may play a role in the hypoxic regulation of hypoxia-inducible factor (HIF)-1. We investigated the role of tyrosine kinase phosphorylation and of the Shc/Ras cascade on hypoxic HIF-1 stabilization. Exposure of human umbilical vein endothelial cells to hypoxia results in HIF protein stabilizati...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000024412.24491.ca
更新日期:2002-07-12 00:00:00
abstract::Isolated cardiac conduction disease is an autosomal dominant defect that includes various combinations of bundle branch or fascicular blocks. These defects can cause sudden death due to a complete heart block. We used a genome-wide screening approach with polymorphic (CA)n repeat markers to determine the chromosomal p...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.77.4.735
更新日期:1995-10-01 00:00:00
abstract::The aim of this study was to determine the mechanism of action of norepinephrine (NE) on arterial baroreceptors (BRs), with the focus on regularly discharging, presumably myelinated fibers. With the use of an in vitro aortic arch/aortic nerve preparation from rats, BR single-fiber discharge was recorded simultaneously...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.61.3.409
更新日期:1987-09-01 00:00:00
abstract::T-wave alternans (TWA), an ABAB oscillation, has been postulated as the initial pattern in a stepwise progression to higher-order oscillations, culminating in sudden arrhythmic death. The present study is the first to provide experimental evidence to support this intriguing concept. Epicardial and endocardial ECGs fro...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000038887.17976.33
更新日期:2002-10-18 00:00:00
abstract::The use of risk markers has transformed cardiovascular medicine, exemplified by the routine assessment of troponin, for both diagnosis and assessment of prognosis in patients with chest pain. Clinical risk factors form the basis for risk assessment of cardiovascular disease and the addition of biochemical, cellular, a...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.309955
更新日期:2017-01-06 00:00:00
abstract:RATIONALE:Mechanisms underlying diastolic dysfunction need to be better understood. OBJECTIVE:To study the role of titin in diastolic dysfunction using a mouse model of experimental heart failure induced by transverse aortic constriction. METHODS AND RESULTS:Eight weeks after transverse aortic constriction surgery, m...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.246819
更新日期:2011-09-30 00:00:00
abstract::Limitation of infarct size by ischemic/pharmacological pre- and postconditioning involves activation of a complex set of cell-signaling pathways. Multiple lines of evidence implicate the mitochondrial permeability transition pore (mPTP) as a key end effector of ischemic/pharmacological pre- and postconditioning. Incre...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.109.197996
更新日期:2009-06-05 00:00:00
abstract::Stimulation of beta-adrenergic receptors (betaARs) causes apoptosis in adult rat ventricular myocytes (ARVMs). The role of reactive oxygen species (ROS) in mediating betaAR-stimulated apoptosis is not known. Stimulation of betaARs with norepinephrine (10 micromol/L) in the presence of prazosin (100 nmol/L) for 24 hour...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000054624.03539.b4
更新日期:2003-02-07 00:00:00
abstract::Contraction and relaxation of vascular smooth muscle and cardiac myocytes are key physiological events in the cardiovascular system. These events are regulated by second messengers, cAMP and cGMP, in response to extracellular stimulants. The strength of signal transduction is controlled by intracellular cyclic nucleot...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000256354.95791.f1
更新日期:2007-02-16 00:00:00
abstract::It is believed that inotropic agents exert their effects in cardiac muscle via a modulation of Ca2+ cycling; however, the involvement of phospholipase activation and the biochemical pathways participating in inotropic responsiveness remain unclear. The aim of the current study was to determine whether arachidonic acid...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.72.2.376
更新日期:1993-02-01 00:00:00
abstract::Of 145 patients with borderline hypertension, 30% had increased resting cardiac index (QI), whereas the remainder had normal values. The specific aim of this study was to investigate cardiac regulation in patients who had normal resting QI. Eighty-five control subjects were used for comparison. At rest, patients with ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.6.199
更新日期:1975-06-01 00:00:00
abstract::Ca2+ influx through the L-type calcium channel (LTCC) induces Ca2+ release from the sarcoplasmic reticulum (SR) and maintains SR Ca2+ loading. Alterations in LTCC properties, their contribution to the blunted adrenergic responsiveness in failing hearts and their recovery after support with LV assist devices (LVAD) wer...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000033988.13062.7c
更新日期:2002-09-20 00:00:00
abstract::We studied the pulmonary vascular effects of prostacylin, PGI2, in the cat with intact chest under conditions of controlled blood flow. Intralobar injections of PGI2, 0.03--1 microgram, decreased arterial pressure in the perfused lobe in a dose-dependent manner. Inasmuch as lobar blood flow was held constant and left ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.45.3.404
更新日期:1979-09-01 00:00:00