Abstract:
:Although the molecular effectors of apoptotic cell death have been largely annotated over the past 30 years, leading to a strong biological understanding of this process and its importance in cell biology, cell death through necrosis has only recently been accepted as a similarly regulated process with definable molecular effectors. The mitochondria are important and central mediators of both apoptosis and regulated necrosis. In apoptosis, the B-cell leukemia/lymphoma 2 (Bcl-2) family members Bcl-2-associated protein x (Bax) and Bcl-2 homologues antagonist/killer (Bak) undergo oligomerization in the outer mitochondrial membrane resulting in the release of apoptosis inducing substrates and the activation of caspases and nucleases. In contrast, during necrosis the mitochondria become dysfunctional and maladaptive in conjunction with reactive oxygen species production and the loss of ATP production, in part through opening of the mitochondrial permeability transition pore. Although regulated necrosis is caspase-independent, recent evidence has shown that it still requires the apoptotic regulators Bax/Bak, which can regulate the permeability characteristics of the outer mitochondrial membrane in their nonoligomerized state. Here, we review the nonapoptotic side of Bcl-2 family, specifically the role of Bax/Bak in regulated necrotic cell death. We will also discuss how these Bcl-2 family member effectors could be part of a larger integrated network that ultimately decides the fate of a given cell somewhere within a molecular continuum between apoptosis and regulated necrosis.
journal_name
Circ Resjournal_title
Circulation researchauthors
Karch J,Molkentin JDdoi
10.1161/CIRCRESAHA.116.305421subject
Has Abstractpub_date
2015-05-22 00:00:00pages
1800-9issue
11eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.116.305421journal_volume
116pub_type
杂志文章,评审abstract::We have previously shown that a cryoactivatable inactive form of renin, which we have tentatively termed prorenin, occurs in human plasma. Plasma prorenin is measured by subtracting the endogenous plasma renin activity (PRA) from the total renin activity measured after cryoactivation. Cryoactivation is accomplished by...
journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1977-05-01 00:00:00
abstract::Vascular remodeling, rather than vasoconstriction, is believed to account for high vascular resistance in severe pulmonary arterial hypertension (PAH). We have found previously that acute Rho kinase inhibition nearly normalizes PAH in chronically hypoxic rats that have no occlusive neointimal lesions. Here we examined...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000261658.12024.18
更新日期:2007-03-30 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::The spatial and dynamic properties of ventricular fibrillation (VF) may be random or related to cellular electrical properties of the normal heart. Local activation intervals (AIs) in VF may depend on the local refractory period (RP), and sustained VF may require a steep action potential (AP) restitution curve. In gui...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.88.5.e49
更新日期:2001-03-16 00:00:00
abstract::Previous studies have postulated an important role for the inwardly rectifying potassium current (I(K1)) in controlling the dynamics of electrophysiological spiral waves responsible for ventricular tachycardia and fibrillation. In this study, we developed a novel tissue model of cultured neonatal rat ventricular myocy...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.178335
更新日期:2009-02-13 00:00:00
abstract::We hypothesized that both acute and chronic accumulation of myocardial interstitial edema (extravascular fluid [EVF]) would compromise cardiac function. We also postulated that excess fluid within the myocardial interstitial space would potentiate interstitial fibrosis, thus further compromising function. Dogs were di...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.6.1713
更新日期:1991-06-01 00:00:00
abstract:RATIONALE:MicroRNAs modestly suppress their direct mRNA targets, and these direct effects are amplified by modulation of gene transcription pathways. Consequently, indirect mRNA modulatory effects of microRNAs to increase or decrease mRNAs greatly outnumber direct target suppressions. Because microRNAs are products of ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.113.300975
更新日期:2013-06-21 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
abstract::The changes in renal function produced by endogenous synthesis of prostaglandins by the kidney were evaluated by infusing sodium arachidonate, the prescursor of the prostaglandins, into one renal artery of the dog. These changes were compared with those produced by similar infusions on performed prostaglandin (PG) E2 ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.1.197
更新日期:1975-01-01 00:00:00
abstract:RATIONALE:Lymphatic vasculature constitutes a second vascular system essential for immune surveillance and tissue fluid homeostasis. Maturation of the hierarchical vascular structure, with a highly branched network of capillaries and ducts, is crucial for its function. Environmental cues mediate the remodeling process,...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.308825
更新日期:2017-04-14 00:00:00
abstract::Over the last 4 decades, heart transplantation (HTx) has evolved as a mainstream therapy for heart failure. Approximately half of patients needing HTx have organ failure consequent to atherosclerosis. Despite advances in immunosuppressive drugs, long-term success of HTx is limited by the development of a particular ty...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000246086.93555.f3
更新日期:2006-10-13 00:00:00
abstract::Protein kinase C (PKC) is a key mediator of many diverse physiological and pathological responses. Although little is known about the specific in vivo roles of the various cardiac PKC isozymes, activation-induced translocation of PKC is believed to be the primary determinant of isozyme-specific functions. Recently, we...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.86.11.1173
更新日期:2000-06-09 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::Oxidized phospholipids, including oxidation products of palmitoyl-arachidonyl-phosphatidyl choline (PAPC), are mediators of inflammation in endothelial cells (ECs) and known to induce several chemokines, including interleukin-8 (IL-8). In this study, we show that oxidized PAPC (OxPAPC), which accumulates in atheroscle...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000146030.53089.18
更新日期:2004-10-15 00:00:00
abstract::We studied the effects of a thrombolytic agent (t-PA) and a thromboxane synthetase inhibitor (CGS-13080) in a model of myocardial ischemia and reperfusion. Occlusion of the left anterior descending coronary artery for 2 hours followed by 4 hours of reperfusion in anesthetized cats results in a large washout of creatin...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.63.3.621
更新日期:1988-09-01 00:00:00
abstract::Canine cardiac Purkinje cells contain both L- and T-type calcium currents, yet the single Ca2+ channels have not been characterized from these cells. Additionally, previous studies have shown an overlap between the steady-state inactivation and activations curves for L-type Ca2+ currents, suggesting the presence of L-...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.3.456
更新日期:1992-03-01 00:00:00
abstract::The average lifespan of humans is increasing, and with it the percentage of people entering the 65 and older age group is growing rapidly and will continue to do so in the next 20 years. Within this age group, cardiovascular disease will remain the leading cause of death, and the cost associated with treatment will co...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.111.246876
更新日期:2012-04-13 00:00:00
abstract::Age-related diastolic dysfunction is a major factor in the epidemic of heart failure. In patients hospitalized with heart failure, HFpEF is now as common as heart failure with reduced ejection fraction. We now have many successful treatments for heart failure with reduced ejection fraction, while specific treatment op...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.115.302929
更新日期:2014-06-20 00:00:00
abstract::Increasing evidence suggests that endogenous NO inhibits sympathetic outflow in anesthetized animals. However, in a recent study from this laboratory, we were unable to find any evidence of increased renal sympathetic nerve activity (RSNA) in response to blockade of NO synthesis in conscious rabbits. Because angiotens...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.82.4.496
更新日期:1998-03-09 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::Adipose tissue (AT) can accumulate macrophages and secrete several inflammatory mediators. Despite its pivotal role in the progression of chronic inflammatory processes such as atherosclerosis, the adaptive role of immunity in obesity remains poorly explored. Visceral AT of diet-induced obese C57BL/6 mice had higher n...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.177105
更新日期:2008-08-29 00:00:00
abstract::The contribution of centrally originating sympathetic activity to the myocardial extracellular accumulation of noradrenaline during the early phase of ischemia has been assessed in a perfused (Langendorff) rat heart preparation isolated except for its sympathetic innervation. A 10-minute electrical stimulation (4 Hz, ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.55.5.702
更新日期:1984-11-01 00:00:00
abstract::Matrix metalloproteinases (MMPs) and, in particular, MMP-9 are important for smooth muscle cell (SMC) migration into the intima. In this study, we sought to determine whether MMP-9 is critical for SMC migration and for the formation of a neointima by using mice in which the gene was deleted (MMP-9(-/-) mice). A denudi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000040420.17366.2e
更新日期:2002-11-01 00:00:00
abstract::Ventricular/vascular coupling dynamics and regional hemodynamics of five hypertensive baboons with concentric left ventricular (LV) hypertrophy (mean arterial pressure +/- SD, 148 +/- 16 mm Hg; LV mass/body weight ratio 3.42 +/- 0.8) were compared with five normotensive controls (mean arterial pressure 89 +/- 3 mm Hg;...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.63.4.798
更新日期:1988-10-01 00:00:00
abstract::Myocardial damage due to reperfusion of ischemic tissue is caused primarily by infiltrating neutrophils. Although leukocyte beta2 integrins (CD18) play a critical role, significant neutrophil emigration persists when CD18 is neutralized or absent. This study examined the role of leukocyte beta1 integrin (alpha4) and i...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000013835.53611.97
更新日期:2002-03-22 00:00:00
abstract:RATIONALE:We have recently shown that the bone morphogenetic protein (BMP) antagonist Gremlin 2 (Grem2) is required for early cardiac development and cardiomyocyte differentiation. Our initial studies discovered that Grem2 is strongly induced in the adult heart after experimental myocardial infarction (MI). However, th...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.308700
更新日期:2016-07-22 00:00:00
abstract::Phenotypic switching of vascular smooth muscle cells (VSMCs) is known to play a critical role in the development of atherosclerosis. However, the factors present within lesions that mediate VSMC phenotypic switching are unclear. Oxidized phospholipids (OxPLs), including 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosp...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.186064
更新日期:2009-03-13 00:00:00
abstract::The synthesis of an angiotensin II (A II) antagonist, sarcosyl1-cysteinyl(S-methyl)8-angiotensin II [Sar1-Cys(Me)8-A II], showing partial organ selectivity and properties of a noncompetitive antagonist, is described. The compound was found to be an extremely potent antagonist on vascular smooth muscle both in vitro (p...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.46.5.720
更新日期:1980-05-01 00:00:00
abstract::Cardiovascular disease continues to be the leading cause of death among women in the United States, accounting for ≈1 of every 3 female deaths. Sex-specific data focused on cardiovascular disease have been increasing steadily, yet is not routinely collected nor translated into practice. This comprehensive review focus...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.307547
更新日期:2016-04-15 00:00:00
abstract::Triadin 1 (TRD) is an integral membrane protein that associates with the ryanodine receptor (RyR2), calsequestrin (CASQ2) and junctin to form a macromolecular Ca signaling complex in the cardiac junctional sarcoplasmic reticulum (SR). To define the functional role of TRD, we examined the effects of adenoviral-mediated...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000160609.98948.25
更新日期:2005-04-01 00:00:00