A5076511413- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Iron Metabolism and Disorders
- RNA regulation and disease
- Metabolism and Genetic Disorders
- Cardiomyopathy and Myosin Studies
- Trace Elements in Health
- Viral Infections and Immunology Research
- Cardiovascular Function and Risk Factors
- Adipose Tissue and Metabolism
- Hemoglobinopathies and Related Disorders
- Cancer, Hypoxia, and Metabolism
- Sirtuins and Resveratrol in Medicine
- Erythropoietin and Anemia Treatment
- RNA Research and Splicing
- Autophagy in Disease and Therapy
- Cardiac Fibrosis and Remodeling
- Cardiac electrophysiology and arrhythmias
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Metabolism, Diabetes, and Cancer
- Congenital heart defects research
- Cardiac Ischemia and Reperfusion
- Hemoglobin structure and function
- Heme Oxygenase-1 and Carbon Monoxide
National Chung Hsing University
2024
Northwestern University
2015-2024
Baylor College of Medicine
2023-2024
Renal Research Institute
2020-2024
Cardiovascular Institute Hospital
2017-2021
National Yang Ming Chiao Tung University
2021
China Medical University
2021
The University of Texas MD Anderson Cancer Center
2010-2016
Washington University in St. Louis
2009-2015
Cardiovascular Institute of the South
2014
SIRT2 is a cytoplasmic sirtuin that plays role in various cellular processes, including tumorigenesis, metabolism, and inflammation. Since these processes require iron, we hypothesized directly regulates iron homeostasis. Here, have demonstrated depletion results decrease levels both vitro vivo. Mechanistically, determined maintains by binding to deacetylating nuclear factor erythroid-derived 2-related 2 (NRF2) on lysines 506 508, leading reduction total NRF2 levels. The leads reduced...
Excess cellular iron increases reactive oxygen species (ROS) production and causes damage. Mitochondria are the major site of metabolism ROS production; however, few studies have investigated role mitochondrial in development cardiac disorders, such as ischemic heart disease or cardiomyopathy (CM). We observe increased mice after ischemia/reperfusion (I/R) human hearts with CM, hypothesize that decreasing protects against I/R damage CM. Reducing genetically through cardiac-specific...
Iron is an essential molecule for biological processes, but its accumulation can lead to oxidative stress and cellular death. Due effects, iron implicated in the process of aging neurodegenerative diseases. However, mechanism this increase with aging, whether localized specific compartment(s), are not known. Here, we measured levels different tissues aged mice, demonstrated that while cytosolic non-heme increased liver muscle tissue, only brain cortex exhibits both mitochondrial iron. This...
Significance Iron deficiency is the most common nutrient deficiency, yet cardiomyopathy rarely develops in these patients. We solved this paradox and identified a protective mechanism involving mRNA-binding protein tristetraprolin (TTP), which adjusts mitochondrial function response to iron deficiency. Mice lacking TTP their hearts were phenotypically normal at baseline but developed spontaneous under exhibited increased reactive oxygen species (ROS)-mediated damage hearts. further...
Abstract The p19ARF tumor suppressor limits ribosome biogenesis and responds to hyperproliferative signals activate the p53 checkpoint response. Although its activation of has been well characterized, role ARF in restraining nucleolar production is poorly understood. Here we report use a mass spectroscopic analysis identify protein changes within nucleoli Arf-deficient mouse cells. Through this approach, discovered that limited localization RNA helicase DDX5, which promotes synthesis...
Background Heme is an essential iron‐containing molecule for cardiovascular physiology, but in excess it may increase oxidative stress. Failing human hearts have increased heme levels, with upregulation of the rate‐limiting enzyme synthesis, δ‐aminolevulinic acid synthase 2 ( ALAS 2), which normally not expressed cardiomyocytes. We hypothesized that accumulation (through cardiac overexpression 2) leads to stress and cell death heart. Methods Results first showed levels are mice subjected...
HIV is a pandemic disease, and many cellular systemic factors are known to alter its infectivity replication. Earlier studies had suggested that anemia common in HIV-infected patients; however, higher iron was also observed AIDS patients prior the introduction of antiretroviral therapy (ART). Therefore, relationship between viral infection not well delineated. To address this issue, we altered levels primary CD4(+) T cells showed associated with increased In addition, alone leads iron,...
Sirtuins (SIRT) exhibit deacetylation or ADP-ribosyltransferase activity and regulate a wide range of cellular processes in the nucleus, mitochondria, cytoplasm. The role only sirtuin that resides cytoplasm, SIRT2, development ischemic injury cardiac hypertrophy is not known. In this paper, we show hearts mice with deletion Sirt2 (Sirt2-/-) display improved function after ischemia-reperfusion (I/R) pressure overload (PO), suggesting SIRT2 exerts maladaptive effects heart response to stress....
Patients with type 2 diabetes often present cardiovascular complications; however, it is not clear how promotes cardiac dysfunction. In murine models, deletion of the gene encoding aryl hydrocarbon nuclear translocator (ARNT, also known as HIF1β) in liver or pancreas leads to a diabetic phenotype; role ARNT metabolism unknown. Here, we determined that cardiac-specific Arnt adult mice results rapid development cardiomyopathy (CM) characterized by accumulation lipid droplets. Compared hearts...
Mediator, an evolutionarily conserved multi-protein complex consisting of about 30 subunits, is a key component the polymerase II mediated gene transcription. Germline deletion Mediator subunit 1 (Med1) in mice results mid-gestational embryonic lethality with developmental impairment multiple organs including heart. Here we show that cardiomyocyte-specific Med1 (csMed1-/-) during late gestational and early postnatal development by intercrossing Med1fl/fl to α-MyHC-Cre transgenic within 10...
The role of posttranscriptional metabolic gene regulatory programs in diabetes is not well understood. Here, we show that the RNA-binding protein tristetraprolin (TTP) reduced livers diabetic mice and humans transcriptionally induced response to insulin treatment murine vitro vivo. Liver-specific Ttp-KO (lsTtp-KO) challenged with high-fat diet (HFD) have improved glucose tolerance peripheral sensitivity compared littermate controls. Analysis secreted hepatic factors demonstrated fibroblast...
Abstract Ischaemic heart disease limits oxygen and metabolic substrate availability to the heart, resulting in tissue death. Here, we demonstrate that AMP-activated protein kinase (AMPK)-related Snf1-related (SNRK) decreases cardiac usage mitochondrial uncoupling, protects against ischaemia/reperfusion. Hearts from transgenic mice overexpressing SNRK have decreased glucose palmitate metabolism consumption, but maintained power function. They also exhibit uncoupling 3 (UCP3) uncoupling....
Pregnancy is associated with substantial physiological changes of the heart, and disruptions in these processes can lead to peripartum cardiomyopathy (PPCM). The molecular that cause pathological heart during pregnancy are not well characterized. Here, we show mTORc1 was activated facilitate cardiac enlargement reversed after delivery mice. activation negatively regulated by mRNA-destabilizing protein ZFP36L2 through its degradation Mdm2 mRNA P53 stabilization, leading increased SESN2 REDD1...
ABSTRACT Sirtuins (SIRT) exhibit deacetylation or ADP-ribosyltransferase activity and regulate a wide range of cellular processes in the nucleus, mitochondria cytoplasm. The role only sirtuin that resides cytoplasm, SIRT2, development heart failure (HF) cardiac hypertrophy is not known. In this paper, we show hearts mice with deletion Sirt2 ( -/- ) display improved function after ischemia-reperfusion (I/R) pressure overload (PO), suggesting SIRT2 exerts maladaptive effects response to...
Chronic loss of Augmenter Liver Regeneration (ALR) results in mitochondrial myopathy with cataracts; however, the mechanism for this disorder remains unclear. Here, we demonstrate that ALR, a principal component MIA40/ALR protein import pathway, impaired cytosolic Fe/S cluster biogenesis mammalian cells. Mechanistically, facilitates ATP-binding cassette (ABC)-B8, an inner membrane required cytoplasmic maturation, through physical interaction ABCB8. Downregulation ALR impairs ABCB8 import,...
In this study, polyethylene glycol (PEG) with hydroxyapatite (HA), the incorporation of physical gold nanoparticles (AuNPs), was created and equipped through a surface coating technique in order to form PEG-HA-AuNP nanocomposites. The morphology chemical composition were characterized using scanning electron microscopy (SEM), atomic force (AFM), UV-Vis spectroscopy (UV-Vis), Fourier transform infrared (FTIR), X-ray photoelectron (XPS), contact angle assessment. effects nanocomposites on...
Proper nuclear organization is critical for cardiomyocyte function, because global structural remodeling of morphology and chromatin structure underpins the development progression cardiovascular disease. Previous reports have implicated a role DNA damage in cardiac hypertrophy; however, mechanism this process not well delineated. AMPK (AMP-activated protein kinase) family proteins regulates metabolism response (DDR). Here, we examine whether member family, SNRK (SNF1-related kinase), which...