EPAC1 inhibition protects the heart from doxorubicin-induced toxicity.

Anthracyclines, such as doxorubicin (Dox), are widely used chemotherapeutic agents for the treatment of solid tumors and hematologic malignancies. However, they frequently induce cardiotoxicity leading to dilated cardiomyopathy and heart failure. This study sought to investigate the role of the exchange protein directly activated by cAMP (EPAC) in Dox-induced cardiotoxicity and the potential cardioprotective effects of EPAC inhibition.

Effects of Dichlorvos on cardiac cells: Toxicity and molecular mechanism of action.

In this study we aimed to understand the underlying mechanism of Dichlorvos-induced toxicity in cardiac cells. For this end, cells were treated by 170 μM of Dichlorvos (DDVP) (corresponding to the IC50) and molecular events were monitored by flow cytometry and western blotting. We have first demonstrated that cell exposure to DDVP for 24 h induced cell death by necroptosis.

Triazole fungicide tebuconazole induces apoptosis through ROS-mediated endoplasmic reticulum stress pathway.

Tebuconazole (TEB) is a common triazole fungicide that has been widely applied in the treatment of fungal diseases. It is reported that TEB could exert harmful effects on mammals' health. However, the molecular mechanism involved in TEB toxicity remain undefined.

Ferulic Acid, Pterostilbene, and Tyrosol Protect the Heart from ER-Stress-Induced Injury by Activating SIRT1-Dependent Deacetylation of eIF2α.

Disturbances in Endoplasmic Reticulum (ER) homeostasis induce ER stress, which has been involved in the development and progression of various heart diseases, including arrhythmias, cardiac hypertrophy, ischemic heart diseases, dilated cardiomyopathy, and heart failure. A mild-to-moderate ER stress is considered beneficial and adaptative for heart functioning by engaging the pro-survival unfolded protein response (UPR) to restore normal ER function. By contrast, a severe or prolonged ER stress is detrimental by promoting cardiomyocyte apoptosis through hyperactivation of the UPR pathways.

Spatiotemporal AMPKα2 deletion in mice induces cardiac dysfunction, fibrosis and cardiolipin remodeling associated with mitochondrial dysfunction in males only.

Background: The AMP-activated protein kinase (AMPK) is a major regulator of cellular energetics which plays key role in acute metabolic response and in long-term adaptation to stress. Recent works have also suggested non-metabolic effects.

Methods: To decipher AMPK roles in the heart, we generated a cardio-specific inducible model of gene deletion of the main cardiac catalytic subunit of AMPK (Ampkα2) in mice.

Threat to Asian wild apple trees posed by gene flow from domesticated apple trees and their "pestified" pathogens.

Secondary contact between crops and their wild relatives poses a threat to wild species, not only through gene flow between plants, but also through the dispersal of crop pathogens and genetic exchanges involving these pathogens, particularly those that have become more virulent by indirect selection on resistant crops, a phenomenon known as "pestification." Joint analyses of wild and domesticated hosts and their pathogens are essential to address this issue, but such analyses remain rare. We used population genetics approaches, demographic inference and pathogenicity tests on host-pathogen pairs of wild or domesticated apple trees from Central Asia and their main fungal pathogen, Venturia inaequalis, which itself has differentiated agricultural and wild-type populations.

Tebuconazole induces ROS-dependent cardiac cell toxicity by activating DNA damage and mitochondrial apoptotic pathway.

Tebuconazole (TEB) is a common triazole fungicide that is widely used throughout the world in agriculture applications. We previously reported that TEB induces cardiac toxicity in rats. The aim of this study was to investigate the underlying mechanism of the toxicity induced by TEB in cardiac cells.

Implication of the deacetylase sirtuin-1 on synovial angiogenesis and persistence of experimental arthritis.

Objectives: To decipher the phenotype of endothelial cells (ECs) derived from circulating progenitors issued from patients with rheumatoid arthritis (RA).

Methods: RA and control ECs were compared according to their proliferative capacities, apoptotic profile, response to tumour necrosis factor (TNF)-α stimulation and angiogenic properties. Microarray experiments were performed to identify gene candidates relevant to pathological angiogenesis.

SIRT1 Protects the Heart from ER Stress-Induced Injury by Promoting eEF2K/eEF2-Dependent Autophagy.

Many recent studies have demonstrated the involvement of endoplasmic reticulum (ER) stress in the development of cardiac diseases and have suggested that modulation of ER stress response could be cardioprotective. Previously, we demonstrated that the deacetylase Sirtuin 1 (SIRT1) attenuates ER stress response and promotes cardiomyocyte survival. Here, we investigated whether and how autophagy plays a role in SIRT1-afforded cardioprotection against ER stress.

Inducible Cardiac-Specific Deletion of Sirt1 in Male Mice Reveals Progressive Cardiac Dysfunction and Sensitization of the Heart to Pressure Overload.

Heart failure is associated with profound alterations of energy metabolism thought to play a major role in the progression of this syndrome. SIRT1 is a metabolic sensor of cellular energy and exerts essential functions on energy metabolism, oxidative stress response, apoptosis, or aging. Importantly, SIRT1 deacetylates the peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α), the master regulator of energy metabolism involved in mitochondrial biogenesis and fatty acid utilization.

Disturbed Fatty Acid Oxidation, Endoplasmic Reticulum Stress, and Apoptosis in Left Ventricle of Patients With Type 2 Diabetes.

Chronic heart failure is a common complication in patients with type 2 diabetes mellitus (T2DM). T2DM is associated with disturbed metabolism of fat, which can result in excessive accumulation of lipids in cardiac muscle. In the current study, we assessed mitochondrial oxidation of carbohydrates and fatty acids, lipid accumulation, endoplasmic reticulum (ER) stress, and apoptosis in diabetic left ventricle.

Population Genome Sequencing of the Scab Fungal Species , , and .

The genus comprises fungal species that are pathogens on host plants, including and on apple, on sorbus and on pear. Although the genetic structure of populations has been investigated in detail, genomic features underlying these subdivisions remain poorly understood. Here, we report whole genome sequencing of 87 strains that represent each species and each population within We present a PacBio genome assembly for the EU-B04 reference isolate.

Ice-Age Climate Adaptations Trap the Alpine Marmot in a State of Low Genetic Diversity.

Some species responded successfully to prehistoric changes in climate [1, 2], while others failed to adapt and became extinct [3]. The factors that determine successful climate adaptation remain poorly understood. We constructed a reference genome and studied physiological adaptations in the Alpine marmot (Marmota marmota), a large ground-dwelling squirrel exquisitely adapted to the "ice-age" climate of the Pleistocene steppe [4, 5].

Endoplasmic reticulum stress induces cardiac dysfunction through architectural modifications and alteration of mitochondrial function in cardiomyocytes.

Aims: Endoplasmic reticulum (ER) stress has recently emerged as an important mechanism involved in the pathogenesis of cardiovascular diseases. However, the molecular mechanisms by which ER stress leads to cardiac dysfunction remain poorly understood.

Methods And Results: In this study, we evaluated the early cardiac effects of ER stress induced by tunicamycin (TN) in mice.

Sirtuin 1 regulates pulmonary artery smooth muscle cell proliferation: role in pulmonary arterial hypertension.

Objective: Energy metabolism shift from oxidative phosphorylation toward glycolysis in pulmonary artery smooth muscle cells (PASMCs) is suggested to be involved in their hyperproliferation in pulmonary arterial hypertension (PAH). Here, we studied the role of the deacetylase sirtuin1 (SIRT1) in energy metabolism regulation in PASMCs via various pathways including activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), master regulator of mitochondrial biogenesis.

Approach And Results: Contents of PGC-1α and its downstream targets as well as markers of mitochondrial mass (voltage-dependent anion channel and citrate synthase) were diminished in human PAH PASMCs.

Citrinin induces apoptosis in human HCT116 colon cancer cells through endoplasmic reticulum stress.

The mycotoxin citrinin (CTN) is a natural contaminant of various human foods that may produce serious adverse health problems. Several studies demonstrated that citrinin exerts cytotoxic and genotoxic effects in both in vivo and in vitro systems. However, the precise mechanisms of action (MOA), particularly in intestinal cells remain unclear.

Mitochondria: a central target for sex differences in pathologies.

It is increasingly acknowledged that a sex and gender specificity affects the occurrence, development, and consequence of a plethora of pathologies. Mitochondria are considered as the powerhouse of the cell because they produce the majority of energy-rich phosphate bonds in the form of adenosine tri-phosphate (ATP) but they also participate in many other functions like steroid hormone synthesis, reactive oxygen species (ROS) production, ionic regulation, and cell death. Adequate cellular energy supply and survival depend on mitochondrial life cycle, a process involving mitochondrial biogenesis, dynamics, and quality control via mitophagy.

SIRT1 protects the heart from ER stress-induced cell death through eIF2α deacetylation.

Over the past decade, endoplasmic reticulum (ER) stress has emerged as an important mechanism involved in the pathogenesis of cardiovascular diseases including heart failure. Cardiac therapy based on ER stress modulation is viewed as a promising avenue toward effective therapies for the diseased heart. Here, we tested whether sirtuin-1 (SIRT1), a NAD-dependent deacetylase, participates in modulating ER stress response in the heart.

SIRT1 protects cardiac cells against apoptosis induced by zearalenone or its metabolites α- and β-zearalenol through an autophagy-dependent pathway.

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium in cereals and agricultural products. The major ZEN metabolites are α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL). In the present study, we investigated the underlying mechanism of the toxicity induced by ZEN, α-ZOL and β-ZOL in cardiac cells (H9c2).

Cobalamin and folate protect mitochondrial and contractile functions in a murine model of cardiac pressure overload.

PGC-1α, a key regulator of energy metabolism, seems to be a relevant therapeutic target to rectify the energy deficit observed in heart failure (HF). Since our previous work has shown positive effects of cobalamin (Cb) on PGC-1α cascade, we investigate the protective role of Cb in pressure overload-induced myocardial dysfunction. Mice were fed with normal diet (ND) or with Cb and folate supplemented diet (SD) 3weeks before and 4weeks after transverse aortic constriction (TAC).

Crocin protects human embryonic kidney cells (HEK293) from α- and β-Zearalenol-induced ER stress and apoptosis.

α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL) are the major metabolites of Zearalenone (ZEN) and are known to induce many toxic effects. In the present study, we investigated the involvement of endoplasmic reticulum (ER) stress in α- and β-ZOL-mediated toxicity in human kidney cells (HEK293) and evaluated the effect of a common dietary compound Crocin (CRO), from saffron. We show that α- and β-ZOL treatment induces ER stress as evidenced by the upregulation of the 78 kDa glucose-regulated protein (GRP78) and the Growth arrest and DNA damage-inducible protein (GADD34).

Recombination-prone bacterial strains form a reservoir from which epidemic clones emerge in agroecosystems.

The acquisition of virulence-related genes through horizontal gene transfer can modify the pathogenic profiles of strains and lead to the emergence of new diseases. Xanthomonas arboricola is a bacterial species largely known for the damage it causes to stone and nut fruit trees worldwide. In addition to these host-specific populations called pathovars, many nonpathogenic strains have been identified in this species.