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Article
CRAT links cholesterol metabolism to innate immune responses in the heart
Chronic inflammation is associated with increased risk and poor prognosis of heart failure; however, the precise mechanism that provokes sustained inflammation in the failing heart remains elusive. Here we rep...
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Untargeted metabolomics analysis of ischemia–reperfusion-injured hearts ex vivo from sedentary and exercise-trained rats
The effects of exercise on the heart and its resistance to disease are well-documented. Recent studies have identified that exercise-induced resistance to arrhythmia is due to the preservation of mitochondrial...
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Article
Open AccessEndothelial LRP1 regulates metabolic responses by acting as a co-activator of PPARγ
Low-density lipoprotein receptor-related protein 1 (LRP1) regulates lipid and glucose metabolism in liver and adipose tissue. It is also involved in central nervous system regulation of food intake and leptin ...
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Article
Bone Morphogenetic Protein-Modulator BMPER Regulates Endothelial Barrier Function
The endothelium serves as a selective barrier and controls the exchange of nutrients, hormones, and leukocytes between blood and tissues. Molecular mechanisms contributing to the pathogenesis of endothelial ba...
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Article
Open AccessHSP70-1 is required for interleukin-5-induced angiogenic responses through eNOS pathway
We report a pivotal role for IL-5 as an angiogenic activator. IL-5 increased proliferation, migration and colony tube formation in HUVECs associated with the phosphorylation of ERK and AKT/eNOS, and promoted m...
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Open AccessCHIP−/−-Mouse Liver: Adiponectin-AMPK-FOXO-Activation Overrides CYP2E1-Elicited JNK1-Activation, Delaying Onset of NASH: Therapeutic Implications
Genetic ablation of C-terminus of Hsc70-interacting protein (CHIP) E3 ubiquitin-ligase impairs hepatic cytochrome P450 CYP2E1 degradation. Consequent CYP2E1 gain of function accelerates reactive O2 species (ROS) ...
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Open AccessEmerging evidence of coding mutations in the ubiquitin–proteasome system associated with cerebellar ataxias
Cerebellar ataxia (CA) is a disorder associated with impairments in balance, coordination, and gait caused by degeneration of the cerebellum. The mutations associated with CA affect functionally diverse genes;...
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Article
Diggin′ on U(biquitin): A Novel Method for the Identification of Physiological E3 Ubiquitin Ligase Substrates
The ubiquitin–proteasome system (UPS) plays a central role in maintaining protein homeostasis, emphasized by a myriad of diseases that are associated with altered UPS function such as cancer, muscle-wasting, a...
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Article
Open AccessAnkyrin repeat and SOCS box containing protein 4 (Asb-4) colocalizes with insulin receptor substrate 4 (IRS4) in the hypothalamic neurons and mediates IRS4 degradation
The arcuate nucleus of the hypothalamus regulates food intake. Ankyrin repeat and SOCS box containing protein 4 (Asb-4) is expressed in neuropeptide Y and proopiomelanocortin (POMC) neurons in the arcuate nucl...
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Article
A Good Idea: A Physician’s Perspective on Genetic Counseling for Hypertrophic Cardiomyopathy
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Seek and destroy: The ubiquitin-proteasome system in cardiac disease
The ubiquitin-proteasome system (UPS) is a major proteolytic system that regulates the degradation of intracellular proteins in the heart. The UPS regulates the turnover of misfolded and damaged proteins, in a...
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Article
Breast cancer quality control
Tumorigenesis is regulated by several mechanisms including signalling, transcription and DNA replication. Now a cytoplasmic protein quality-control pathway is implicated in the suppression of breast cancer cel...
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Article
Torturing a blood vessel
Experiments in mice and zebrafish uncover a pathway behind malformed blood vessels in the brain (pages 169–176 & 177–184
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Article
Structural basis of nucleotide exchange and client binding by the Hsp70 cochaperone Bag2
Bag2 acts as a nucleotide-exchange factor for Hsp70 and also binds misfolded substrates. Now structural work reveals that Bag2 promotes nucleotide exchange via a mechanism distinct from other Hsp70 nucleotide-...
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Article
Open AccessTobacco use induces anti-apoptotic, proliferative patterns of gene expression in circulating leukocytes of Caucasian males
Strong epidemiologic evidence correlates tobacco use with a variety of serious adverse health effects, but the biological mechanisms that produce these effects remain elusive.
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Therapeutic options for premature coronary artery disease
Although cardiovascular disease is commonly recognized as a disease of the elderly, young patients are also at risk for coronary atherosclerosis, which has a devastating impact on their more active lifestyle. ...
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Article
CHIP-mediated stress recovery by sequential ubiquitination of substrates and Hsp70
CHIP — a co-chaperone/ubiquitin ligase — not only targets chaperone substrates for degradation, but mediates Hsp70 turnover after misfolded substrates have been depleted. The sequential catalysis of the CHIP-a...
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Article
Shear Stress Reduces Protease Activated Receptor-1 Expression in Human Endothelial Cells
Shear stress has been shown to regulate several genes involved in the thrombotic and proliferative functions of endothelial cells. Thrombin receptor (protease-activated receptor-1: PAR-1) increases at sites of...
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Article
The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins
To maintain quality control in cells, mechanisms distinguish among improperly folded peptides, mature and functional proteins, and proteins to be targeted for degradation. The molecular chaperones, including h...
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Article
The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation
The folding of both wild-type and mutant forms of the cystic-fibrosis transmembrane-conductance regulator (CFTR), a plasma-membrane chloride-ion channel, is inefficient1,2,3,4. Most nascent CFTR is retained in th...