A5023542009- Autophagy in Disease and Therapy
- Cardiac Imaging and Diagnostics
- Coronary Interventions and Diagnostics
- Mitochondrial Function and Pathology
- Cerebrovascular and Carotid Artery Diseases
- Cardiovascular Function and Risk Factors
- Coronary Artery Anomalies
- Endoplasmic Reticulum Stress and Disease
- Signaling Pathways in Disease
- Acute Myocardial Infarction Research
- Advanced MRI Techniques and Applications
- GABA and Rice Research
- Metabolism, Diabetes, and Cancer
- Cardiac Fibrosis and Remodeling
- Sirtuins and Resveratrol in Medicine
- Calcium signaling and nucleotide metabolism
- Cardiac pacing and defibrillation studies
- Heart Failure Treatment and Management
- Venous Thromboembolism Diagnosis and Management
- Adenosine and Purinergic Signaling
- Cardiac Structural Anomalies and Repair
- PI3K/AKT/mTOR signaling in cancer
- Peripheral Artery Disease Management
- Parkinson's Disease Mechanisms and Treatments
- Cardiovascular Issues in Pregnancy
Osaka University
2010-2025
British Heart Foundation
2017-2024
King's College London
2016-2024
Osaka City University
2012
Osaka Gakuin University
2011
Osaka Police Hospital
2005-2008
AbstractConstitutive autophagy is important for control of the quality proteins and organelles to maintain cell function. Damaged accumulate in aged organs. We have previously reported that cardiac-specific Atg5 (autophagy-related gene 5)-deficient mice, which was floxed out early embryogenesis, were born normally, showed normal cardiac function structure up 10 weeks old. In present study, determine longer-term consequences Atg5-deficiency heart, we monitored Atg5-deficient mice further 12...
Abstract Damaged mitochondria are removed by mitophagy. Although Atg32 is essential for mitophagy in yeast, no homologue has been identified mammalian cells. Here, we show that Bcl-2-like protein 13 (Bcl2-L-13) induces mitochondrial fragmentation and First, hypothesized unidentified receptors would share molecular features of Atg32. By screening the public database homologues, identify Bcl2-L-13. Bcl2-L-13 binds to LC3 through WXXI motif HEK293 In Bcl2-L-13, BH domains important...
Highlights•Atg32 and Bcl2-L-13 are yeast mammalian mitophagy receptors, respectively•Atg1 complex is essential for Bcl2-L-13- but not Atg32-mediated mitophagy•ULK1 necessary Bcl2-L-13-mediated in cellsSummaryDegradation of mitochondria by selective autophagy, termed mitophagy, contributes to the control mitochondrial quality. a homolog Atg32, which an receptor yeast. However, molecular machinery involved remains be elucidated. Here, we show that ULK1 (unc-51-like kinase) required process...
Heart failure is a major public health problem, and abnormal iron metabolism common in patients with heart failure. Although necessary for metabolic homeostasis, it induces programmed necrosis. Iron release from ferritin storage through nuclear receptor coactivator 4 (NCOA4)-mediated autophagic degradation, known as ferritinophagy. However, the role of ferritinophagy stressed remains unclear. Deletion Ncoa4 mouse hearts reduced left ventricular chamber size improved cardiac function along...
In heart failure patients, the accumulation of damaged mitochondria is frequently observed in cardiomyocytes. Damaged are degraded through mitophagy, a form mitochondria-specific autophagy. Previously, we identified BCL2L13 as mitophagy receptor and demonstrated its ability to induce mitochondrial fission mammalian cells necessity phosphorylation at Ser272 for activation. However, vivo role remains unclear. this study, investigated cardiac function using bcl2l13 knockout mice knock-in...
Calpains make up a family of Ca(2+)-dependent intracellular cysteine proteases that include ubiquitously expressed μ- and m-calpains. Both are heterodimers consisting distinct large catalytic subunit (calpain 1 for μ-calpain calpain 2 m-calpain) common regulatory 4). The physiological roles remain unclear in the organs, including heart, but it has been suggested is activated by Ca(2+) overload diseased hearts, resulting cardiac dysfunction. In this study, cardiac-specific 4-deficient mice...
Cardiomyocytes proliferate during fetal life but lose their ability to soon after birth and further increases in cardiac mass are achieved through an increase cell size or hypertrophy. Mammalian target of rapamycin complex 1 (mTORC1) is critical for growth proliferation. Rheb (Ras homologue enriched brain) one the most important upstream regulators mTORC1. Here, we attempted clarify role heart using cardiac-specific Rheb-deficient mice (Rheb(-/-)). Rheb(-/-) died from postnatal day 8 10. The...
Highlights•This study is the first to identify in vivo role of FKBP8 heart.•Cardiac-specific FKBP8-deficient mice were generated.•FKBP8 plays a cardio-protective response pressure overload.•FKBP8 has anti-apoptotic functions via endoplasmic reticulum-mediated pathway.•FKBP8 prevents accumulation misfolded proteins.AbstractProtein quality control cardiomyocytes crucial maintain cellular homeostasis. The damaged organelles, such as mitochondria and proteins heart associated with failure....
Mitochondrial deoxyribonucleic acid, containing the unmethylated cytidine-phosphate-guanosine motif, stimulates Toll-like receptor 9 to induce inflammation and heart failure. A small chemical, E6446 [(6-[3-(pyrrolidin-1-yl)propoxy)-2-(4-(3-(pyrrolidin-1-yl)propoxy)phenyl]benzo[d]oxazole)], is a specific inhibitor in cardiomyocytes. In this study, we showed that exerts beneficial effects for prevention treatment of pressure overload-induced failure mice. When administered before operation...
Proinflammatory cytokines play an important role in the pathogenesis of heart failure. The mechanisms responsible for maintaining sterile inflammation within failing hearts remain poorly defined. Although transcriptional control is proinflammatory cytokine gene expression, stability mRNA also contributes to kinetics immune responses. Regnase-1 RNase involved degradation a set mRNAs cells. nonimmune cells such as cardiomyocytes remains be elucidated.
A subset of cardiac fibroblasts responds to pressure overload by recruiting inflammatory monocytes the heart.
Heart failure has high morbidity and mortality in the developed countries. Autophagy is important for quality control of proteins organelles heart. Rubicon (Run domain Beclin-1-interacting cysteine-rich domain-containing protein) been identified as a potent negative regulator autophagy endolysosomal trafficking. The aim this study was to investigate vivo role Rubicon-mediated endosomal trafficking We generated cardiomyocyte-specific Rubicon-deficient mice subjected pressure overload by means...
Abstract Heart failure is a leading cause of mortality in developed countries. Cell death key player the development heart failure. Calcium-independent phospholipase A 2 β (iPLA β) produces lipid mediators by catalyzing lipids and induces nuclear shrinkage caspase-independent cell death. Here, we show that lysophosphatidylserine generated iPLA necrotic cardiomyocyte death, as well contractile dysfunction mediated through its receptor, G protein-coupled receptor 34 (GPR34)....