Differential impact of doxorubicin dose on cell death and autophagy pathways during acute cardiotoxicity.

Doxorubicin (DOX) is an effective anthracycline used in chemotherapeutic regimens for a variety of haematological and solid tumors. However, its utility remains limited by its well-described, but poorly understood cardiotoxicity. Despite numerous studies describing various forms of regulated cell death and their involvement in DOX-mediated cardiotoxicity, the predominate form of cell death remains unclear.

Correction to: Myocardin regulates mitochondrial calcium homeostasis and prevents permeability transition.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Misoprostol regulates Bnip3 repression and alternative splicing to control cellular calcium homeostasis during hypoxic stress.

The cellular response to hypoxia involves the activation of a conserved pathway for gene expression regulated by the transcription factor complex called hypoxia-inducible factor (HIF). This pathway has been implicated in both the adaptive response to hypoxia and in several hypoxic-ischemic-related pathologies. Perinatal hypoxic injury, often associated with prematurity, leads to multi-organ dysfunction resulting in significant morbidity and mortality.

Myocardin regulates mitochondrial calcium homeostasis and prevents permeability transition.

Myocardin is a transcriptional co-activator required for cardiovascular development, but also promotes cardiomyocyte survival through an unclear molecular mechanism. Mitochondrial permeability transition is implicated in necrosis, while pore closure is required for mitochondrial maturation during cardiac development. We show that loss of myocardin function leads to subendocardial necrosis at E9.

Human Milk Fortification Increases Bnip3 Expression Associated With Intestinal Cell Death In Vitro.

Objectives: The aim of the present study was to determine the in vitro effect(s) of a bovine-based human breast milk fortifier (HMF) on human intestinal cells. HMF increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein (Bnip3) and cell death; the prostaglandin analogue misoprostol will rescue this effect.

Methods: Cultured intestinal cells were exposed to in vitro-digested human breast milk (BM) ± HMF.

Targeting skeletal muscle mitochondria to prevent type 2 diabetes in youth.

The prevalence of type 2 diabetes (T2D) has increased dramatically over the past two decades, not only among adults but also among adolescents. T2D is a systemic disorder affecting every organ system and is especially damaging to the cardiovascular system, predisposing individuals to severe cardiac and vascular complications. The precise mechanisms that cause T2D are an area of active research.

Striking a balance: autophagy, apoptosis, and necrosis in a normal and failing heart.

Despite the progress that has been made over the past two decades in cardiovascular research, heart failure remains a major cause of morbidity and mortality worldwide. Insight into the cellular and molecular mechanisms that underlie the heart failure in individuals with ischemic heart disease have identified defects in cellular processes that govern autophagy, apoptosis and necrosis as a prevailing underlying cause. Indeed, programmed cell death of cardiac cells by apoptosis or necrosis is believed to involve the intrinsic mitochondrial pathway and/or extrinsic death receptor pathway by certain Bcl-2 family members as well as components of the TNFα signaling pathway.

Cell death signalling mechanisms in heart failure.

Cardiac disease is a global epidemic that is on the rise, despite the recent advances in cardiovascular research. Once the myocardium is injured, it has a limited capacity to activate reparative mechanisms to restore proper cardiac function, leading to the development of systemic heart failure. Autophagy, under certain conditions, may result in cell death, further emphasizing the controversial issues regarding the autophagic process as an adaptive or maladaptive biological response.

Epigenetic regulation of E2F-1-dependent Bnip3 transcription and cell death by nuclear factor-κB and histone deacetylase-1.

A delicate balance exists between cell growth and cell death. In the context of the adult myocardium, inappropriate or inordinate cell loss through an apoptotic process may profoundly influence cardiac structure, function, or both given the limited and meager ability of the heart for repair after injury. Earlier work by the authors' laboratory identified a close relation between cell cycle factor E2F-1 and hypoxia-inducible factor Bnip3 as the key regulator of apoptosis and autophagy in ventricular myocytes.