Abstract:
BACKGROUND:Heat shock protein (HSP)60 is an abundant protein found primarily in the mitochondria, though 15% to 20% is found in the cytosol. Previously we observed that HSP60 complexes with bax in the cytosol. Reduction in HSP60 precipitates translocation of bax to the mitochondria and apoptosis. We hypothesized that HSP60 would decrease with hypoxia/reoxygenation and that this would precipitate bax translocation to the mitochondria and release of cytochrome c. METHODS AND RESULTS:Adult rat cardiac myocytes were studied at end-hypoxia and at 10 and 24 hours of reoxygenation. HSP60 levels were unchanged at end-hypoxia and decreased 33% and 40% at 10 and 24 hours of reoxygenation, whereas HSP72 increased 80% and 110%. Bax and bcl-2 decreased during reoxygenation. However, cytochrome c release occurred at end-hypoxia, before reoxygenation. Cell fractionation was done to analyze this further. In normal myocytes, bax and HSP60 were present in the cytosol, and bax coimmunoprecipitated with cytosolic HSP60. At end-hypoxia, mitochondrial HSP60 was unchanged, but cytosolic HSP60 had disappeared and was now in the plasma membrane fraction. Concurrently, bax was no longer in the cytosol but now in the mitochondria. Thus, although total HSP60 remained the same, it no longer complexed with bax, and bax was free to translocate to the mitochondria and precipitate apoptosis. Reduction in ATP had a similar effect. CONCLUSIONS:These studies show that hypoxia results in disassociation of the HSP60-bax complex with translocation of cytosolic HSP60 to the plasma membrane and bax to the mitochondria. This is sufficient to trigger apoptosis.
journal_name
Circulationjournal_title
Circulationauthors
Gupta S,Knowlton AAdoi
10.1161/01.cir.0000038112.64503.6esubject
Has Abstractpub_date
2002-11-19 00:00:00pages
2727-33issue
21eissn
0009-7322issn
1524-4539journal_volume
106pub_type
杂志文章相关文献
CIRCULATION文献大全abstract:BACKGROUND:The metabolic syndrome is associated with increased angiotensin II activity, induction of a proinflammatory and oxidative state, and endothelial dysfunction. We evaluated the ability of irbesartan, an angiotensin receptor blocker, and lipoic acid, an antioxidant, to affect endothelial function and inflammati...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1161/01.CIR.0000153272.48711.B9
更新日期:2005-01-25 00:00:00
abstract::A clinical study was conducted to evaluate the efficacy and safety of percutaneous coronary excimer laser angioplasty in 60 patients with coronary artery disease. Forty-nine patients had stable exertional angina, and 11 patients had unstable angina despite medical therapy. A novel 1.4-mm diameter catheter with 20 quar...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.81.6.1849
更新日期:1990-06-01 00:00:00
abstract::Diffuse coronary artery disease is frequently untreatable by coronary artery bypass or angioplasty. Many such "no-option" patients have been subjects for trials of angiogenesis using growth factor manipulation or laser injury. We think these novel revascularization strategies are limited by insufficient inflow to puta...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.103.21.2539
更新日期:2001-05-29 00:00:00
abstract:BACKGROUND:Recent studies have suggested that endogenous erythropoietin (Epo) plays an important role in the mobilization of bone marrow-derived endothelial progenitor cells (EPCs). However, it remains to be elucidated whether the Epo system exerts protective effects on pulmonary hypertension (PH), a fatal disorder enc...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.105.583732
更新日期:2006-03-21 00:00:00
abstract:BACKGROUND:The effect of isoproterenol on increasing the peak amplitude of the L-type calcium current is reduced in myocytes dispersed from the epicardial border zone (EBZ) of the 5-day infarcted canine heart when compared with control cells from noninfarcted hearts. This suggests that specific alterations in the beta-...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.91.11.2824
更新日期:1995-06-01 00:00:00
abstract:BACKGROUND:The clinical significance of the interaction between clopidogrel and proton pump inhibitors (PPIs) remains unclear. METHODS AND RESULTS:We examined the relationship between PPI use and 1-year cardiovascular events (cardiovascular death, myocardial infarction, or stroke) in patients with acute coronary syndr...
journal_title:Circulation
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1161/CIRCULATIONAHA.111.032912
更新日期:2012-02-28 00:00:00
abstract:BACKGROUND:The effect of the increasing prevalence of obesity on blood pressure (BP) secular trends is unclear. We analyzed BP and body mass index secular trends between 1998 and 2006 in children and adolescents of the Seychelles, a rapidly developing island state in the African region. METHODS AND RESULTS:School-base...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.108.796276
更新日期:2009-02-03 00:00:00
abstract:BACKGROUND:Hypercholesterolemia is a risk factor for coronary disease, and platelet reactivity is increased with hypercholesterolemia, suggesting a prethrombotic risk. The aim of this study was to measure mural platelet thrombus formation on an injured arterial wall in a model simulating vessel stenosis and plaque rupt...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.92.11.3172
更新日期:1995-12-01 00:00:00
abstract:BACKGROUND:Poststroke angiogenesis contributes to long-term recovery after stroke. Signal transducer and activator of transcription-3 (Stat3) is a key regulator for various inflammatory signals and angiogenesis. It was the aim of this study to determine its function in poststroke outcome. METHODS AND RESULTS:We genera...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.114.013003
更新日期:2015-05-19 00:00:00
abstract:BACKGROUND:Human endothelial and vascular smooth muscle cells synthesize prostanoids. Several of these have been implicated in the physiological and pathophysiological regulation of vascular tone; however, there is no direct evidence that human blood vessels synthesize sufficient prostanoid to alter vessel tone. METHO...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.92.8.2113
更新日期:1995-10-15 00:00:00
abstract:BACKGROUND:The identification of sites of dominant activation frequency during atrial fibrillation (AF) in humans and the effect of ablation at these sites have not been reported. METHODS AND RESULTS:Thirty-two patients undergoing AF ablation (19 paroxysmal, 13 permanent) during ongoing arrhythmia were studied. Electr...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.104.517011
更新日期:2005-08-09 00:00:00
abstract:BACKGROUND:Application of pyruvate was shown to improve contractile function in isolated animal myocardium and hemodynamics in patients with congestive heart failure. We assessed the influence of pyruvate on systolic and diastolic myocardial function and its subcellular mode of action in isolated myocardium from end-st...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/hc0202.102238
更新日期:2002-01-15 00:00:00
abstract:BACKGROUND:Metabolic syndrome importantly accelerates the atherosclerotic process, the earliest event of which is endothelial dysfunction. Ghrelin, a gastric peptide with cardiovascular actions, has been shown to inhibit proatherogenic changes in experimental models. This study therefore investigated whether ghrelin ad...
journal_title:Circulation
pub_type: 临床试验,杂志文章
doi:10.1161/CIRCULATIONAHA.105.553883
更新日期:2005-11-08 00:00:00
abstract::Ten subjects with normal hemodynamics were studied during elective cardiac catheterization with right and left heart multisensor micromanometry to assess hemodynamic responses to the Mueller maneuver. Simultaneous right and left circulatory hemodynamics and left ventricular, pulmonary arterial, and aortic pressures we...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.76.5.1020
更新日期:1987-11-01 00:00:00
abstract:BACKGROUND:Two phase III trials of enoxaparin for unstable angina/non-Q-wave myocardial infarction have shown it to be superior to unfractionated heparin for preventing a composite of death and cardiac ischemic events. A prospectively planned meta-analysis was performed to provide a more precise estimate of the effects...
journal_title:Circulation
pub_type: 临床试验,杂志文章,meta分析,多中心研究
doi:10.1161/01.cir.100.15.1602
更新日期:1999-10-12 00:00:00
abstract::The ability of predischarge quantitative exercise thallium-201 (201T1) scintigraphy to predict future cardiac events was evaluated prospectively in 140 consecutive patients with uncomplicated acute myocardial infarction; the results were compared with those of submaximal exercise treadmill testing and coronary angiogr...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.68.2.321
更新日期:1983-08-01 00:00:00
abstract:BACKGROUND:Chemokines play an essential role in regulating the infiltration of leukocytes into allografts in experimental models. Little is known of their expression or function after human cardiac transplantation. METHODS AND RESULTS:We analyzed 169 sequential human endomyocardial biopsies by immunocytochemistry for ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/hc4601.098010
更新日期:2001-11-20 00:00:00
abstract::A patient is described in whom a large congenital aneurysm or diverticulum of the right atrium caused repeated attacks of supraventricular arrhythmia and a strikingly reduced cardiac output. The aneurysm, which contained a large thrombus, was demonstrated by preoperative angiographic examinations. At the time of opera...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.38.1.124
更新日期:1968-07-01 00:00:00
abstract:BACKGROUND:Adenosine is believed to be cardioprotective; however, it has not been elucidated whether the plasma adenosine level is increased in chronic heart failure. METHODS AND RESULTS:Seventy-one patients attending a specialized heart failure clinic during a 6-month period were grouped according to the cause of chr...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.95.6.1363
更新日期:1997-03-18 00:00:00
abstract:BACKGROUND:Prolonged metabolic abnormalities have been demonstrated previously in postischemic myocardium, including relative increases in glucose uptake and abnormal fatty acid kinetics. However, quantitative metabolic information is limited, and the time course of changes in MVO2 in postischemic myocardium is unknown...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.85.5.1842
更新日期:1992-05-01 00:00:00
abstract:BACKGROUND:Although black cardiac patients receive fewer revascularization procedures than whites, it is unclear whether this has a detrimental impact on outcomes. The objective of our study was to compare 6-month functional status and angina outcomes among blacks and whites with documented coronary disease and to asse...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000157731.66268.E1
更新日期:2005-03-15 00:00:00
abstract:BACKGROUND:Hutchinson-Gilford progeria syndrome is an ultrarare segmental premature aging disease resulting in early death from heart attack or stroke. There is no approved treatment, but starting in 2007, several recent single-arm clinical trials administered inhibitors of protein farnesylation aimed at reducing toxic...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.113.008285
更新日期:2014-07-01 00:00:00
abstract::We examined the cardiopulmonary effects of maximum bicycle ergometer exercise in seven patients with implanted Intermedics Nova MR pacemakers for three types of pacing in a randomized sequence: VVI or AAI at 70 beats/min (SSI 70), rate-adaptive temperature-controlled pacing with the implanted Nova MR, and rate-adaptiv...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1988-11-01 00:00:00
abstract::A consecutive series of 17 patients surgically treated for asymptomatic coronary artery disease was surveyed for survival, clinical status, and graft patency after a mean follow-up of 75 months. Documented myocardial infarction (MI), 14 transmural and 3 subendocardial, was the major indication for catheterization. All...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.60.2.14
更新日期:1979-08-01 00:00:00
abstract::Syncope and sudden death occurs in certain purebred Pug dogs which have been found to have intermittent sinus pauses and paroxysmal second degree heart block on electrocardiographic (ECG) study. We have established a colony of such dogs to study this problem and here report the results of histological examination of t...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.52.6.1152
更新日期:1975-12-01 00:00:00
abstract:BACKGROUND:Candidates for cardiac resynchronization therapy (CRT) receive either a biventricular pacemaker or a biventricular pacemaker with an implantable cardioverter-defibrillator (CRT-D). Optimal device selection remains challenging because the benefit of implantable cardioverter-defibrillator therapy may not be un...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.115.018830
更新日期:2016-01-19 00:00:00
abstract:BACKGROUND:Recent in vitro studies have shown that disturbed flow and oxidative conditions induce the expression of bone morphogenic proteins (BMPs 2 and 4) in cultured endothelial cells. BMPs can stimulate superoxide production and inflammatory responses in endothelial cells, raising the possibility that BMPs may play...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.106.611822
更新日期:2006-06-20 00:00:00
abstract:BACKGROUND:Laminins are major components of basement membranes, well located to interact with platelets upon vascular injury. Laminin-111 (α1β1γ1) is known to support platelet adhesion but is absent from most blood vessels, which contain isoforms with the α2, α4, or α5 chain. Whether vascular laminins support platelet ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.112.000799
更新日期:2013-07-30 00:00:00
abstract:BACKGROUND:Posteroseptal ablation of the atrioventricular node (AVN) has been proposed as a means to slow the ventricular rate during atrial fibrillation (AF). The suggested mechanism is elimination of the AVN "slow pathway." On the basis of the unpredictable success of the procedure, we hypothesize that, in fact, the ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.99.17.2323
更新日期:1999-05-04 00:00:00
abstract:BACKGROUND:The combination of a single-bolus fibrinolytic and a low-molecular-weight heparin may facilitate prehospital reperfusion and further improve clinical outcome in patients with ST-elevation myocardial infarction. METHODS AND RESULTS:In the prehospital setting, 1639 patients with ST-elevation myocardial infarc...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1161/01.CIR.0000081659.72985.A8
更新日期:2003-07-15 00:00:00