We previously demonstrated that indoxyl sulfate (IS), a uremic toxin, induces aortic calcification in hypertensive rats, and induces oxidative stress and the expression of osteoblast-specific proteins in vascular smooth muscle cells. This study aimed to clarify whether IS stimulates senescence of cultured human aortic smooth muscle cells (HASMCs) and aorta ...

Hyperhomocysteinemia (HHcy) is a risk factor for vascular disease but its underlying molecular pathology is not understood. Homocysteine is metabolically linked to the epigenetic process of DNA methylation. Tissue-specific changes in DNA methylation have been observed in HHcy but little is known about vascular tissue. The objective of this study ...

AIMS: This study sought to assess the effect of sphingomyelin synthase 2 (SMS2) over-expression on plaque component and endothelial dysfunction in atherosclerosis. MAIN METHODS: We generated recombinant adenovirus vectors containing human SMS2 cDNA (AdV-SMS2) or control gene GFP cDNA (AdV-GFP). Both AdVs were injected (i.v.) into ApoE KO mice to ...

About 1-2% of the population present with bicuspid aortic valves (BAV), a defect of the aortic valve resulting in the formation of two leaflets instead of three. This disease leads to an abnormal aorta, altered in strength and size, which in turn is a high risk factor for potentially lethal ...

Vascular calcification is a pathobiological process which leads to high morbidity and mortality in cardiovascular disease. The association between vascular calcification and osteoporosis has been reported widely, and there are close relationships among vascular calcification, related cardiovascular disease and osteoporosis, but the biochemical mechanism of vascular calcification is presently unclear. ...

The aim was to analyze the effect of tacrolimus on the aortic expression of proteins associated with the energetic metabolism and cytoskeleton and if it could be reverted by ET-1-receptor antagonist bosentan. Wistar Kyoto rats were divided into: control (n=10), tacrolimus (n=10, 0.5mg/kg bw/day tacrolimus for 30days) and tacrolimus+bosentan (n=10, ...

NADPH oxidase Nox5 subtype expression is significantly increased in vascular smooth muscle cells (SMCs) underlying fibro-lipid atherosclerotic lesions. The mechanisms that up-regulate Nox5 are not understood. Consequently, we characterized the promoter of the human Nox5 gene and investigated the role of various pro-inflammatory transcription factors in the regulation of Nox5 ...

Using a fluorescence method called colocalization single-molecule spectroscopy (CoSMoS), Friedman and Gelles dissect the kinetics of transcription initiation at a bacterial promoter. Ultimately, CoSMoS could greatly aid the study of the effects of DNA sequence and transcription factors on both prokaryotic and eukaryotic promoters.

To explore the mechanism of Toll-like receptor (TLR4) inhibition in the delay of formation of atherosclerosis by herb-partition moxibustion. Seventy-five rabbits were randomly assigned to one of five groups: blank, atherosclerosis (AS) model, direct moxibustion, herb-partition moxibustion, and drug treatment. With the exception of the blank group, all rabbits were ...

We recently reported that peptidoglycan (PGN), a cell wall component of the Gram-positive bacterium, induces NF-κB activation and microglia activation. However, PGN-regulated AP-1 activation and cytokine expression in microglia remains unclear. This study investigated how PGN influences the signaling pathway involved in IL-6 production in microglia. IL-6 mRNA and protein ...

Non-proteolytic group 2 allergen, Der p 2 (DP2) is known as a major allergen derived from house dust mite Dermatophagoides pteronyssinus.Paracellular epithelial barrier, being composed of a number of tight junction (TJ) molecules, plays pivotal roles in resistance of pathogen invading. However, whether DP2 affects epithelial TJ molecules is unclear. ...

Glypican-3 (GPC3) is a developmentally-regulated oncofetal protein that has been established as a clinically-relevant biomarker for early hepatocellular carcinoma (HCC). It is one of the first transcripts to appear during malignant hepatocyte transformation, and is expressed at the protein level in approximately half of high-grade dysplastic macronodules in cirrhotic liver. ...

Background:  Cockroaches have been identified as one of the major indoor allergens inducing perennial rhinitis and asthma. Per a 1s are a group of the major allergens from American cockroach. Although Per a 1s are major allergens from American cockroach, factors contributing to the allergenicity of Per a 1s are ...

The minor coat protein of the avian reovirus (ARV), σC, encoded by the S1 genome segment, is one of the major candidates for the development of a subunit vaccine against ARV infection. To develop a plant-based vaccine to immunize poultry against ARV infection, we constructed 4 plant nuclear expression vectors ...

We recently showed that poly(ADP-ribose)polymerase-1 (PARP-1) may play a role in allergen (ovalbumin)-induced airway eosinophilia, potentially through a specific effect on IL-5 production. We also reported that while IL-5 replenishment promotes reversal of eosinophilia in lungs of PARP-1(-/-) mice, IL-4 or Immunoglobulin E replenishment do not, suggesting a potentially significant ...

The T-box transcription factor TBX3 provides an important link between embryonic development and cancer. TBX3 mediates limb, mammary gland and heart development and, in humans, mutations resulting in haplo-insufficiency of TBX3 lead to ulnar-mammary syndrome. Importantly, the de-regulation of TBX3 gene expression has been linked to several cancers, where it ...

Activating transcription factor 2 (ATF-2), c-Fos, and c-Jun belong to the bZIP family of transcription factors. Promoters of c-Fos, c-Jun, cyclin D1, and cyclin A are targets of ATF-2 in primary mouse chondrocytes. An ATF-2 expression vector was co-transfected with either c-Fos or c-Jun promoters in mutant ATF-2 chondrocytes in ...

The pathogenesis of necrotizing enterocolitis (NEC) is unknown. Ischemia and reperfusion (I/R) injury have been considered to be major contributing factors. More recent reports have noted that apoptosis is a significant and perhaps the principal contributor to cell death after I/R injury. Recent studies have revealed that activator protein 1 ...

Andrographis paniculata is an herb widely used in China, Korea, and India for its anti-hepatotoxic, anti-viral, and anti-inflammatory effects. Andrographolide is the major bioactive diterpene lactone in A. paniculata. The pi class of glutathione S-transferase (GSTP) is one of the phase II biotransformation enzymes. Our previous study indicated that andrographolide ...

The transcription factor p63 belongs to the p53 protein family and plays an important role in epithelial development. Recent studies showed that p63 is over-expressed in some human squamous cell carcinomas of the head and neck, suggesting a role in carcinogenesis. The p63 gene contains two promoters and alternative promoter ...

Human serum paraoxonase 1 (PON1), an arylesterase, is associated with high-density lipoprotein (HDL) and can inhibit the oxidative modification of low-density lipoprotein (LDL), implying that PON1 may prevent atherosclerosis. Berberine, a botanical alkaloid, lowers the cholesterol level in serum and is thought to display cardioprotective properties. However, the effect of ...

Hypoxia is the most important factor in the pathogenesis of diabetic retinopathy. Cysteine-rich 61 (Cyr61) is one of the angiogenic factors involved in the development of proliferative diabetic retinopathy (PDR). The aim of this study was to investigate the mechanism of hypoxia-induced Cyr61 expression in retinal vascular endothelial cells. The ...

Ran (Ras-related nuclear protein), a Ras family GTPase, is involved in multiple cellular functions, including the regulation of DNA replication, cell cycle progression, nuclear structure formation, RNA processing-exportation, and nuclear protein importation. Ran(+/-) embryonic stem (ES) cells were produced in an attempt to generate Ran null mutant mice. Even after ...

With-no-lysine (K) kinase-4 (WNK4) is a serine/threonine protein kinase and plays a crucial role in the regulation of blood pressure and electrolyte homeostasis. Whether or not estrogen, an important regulator of physiologic functions, modulates human WNK4 (hWNK4) gene expression is unknown. In the current study, real-time PCR assay showed that ...

Many cases of sudden chlorpromazine (Chl)-related deaths have been identified in forensic autopsies. Because Chl concentration detected in such cases is often low, identifying the cause of death can be difficult. Patients on Chl therapy exhibit arrhythmia and cardiomyopathy. Thus, Chl may affect the heart, particularly, gene expression there. Immediate ...

Preeclampsia (PE) is a serious disorder of human pregnancy, it is often associated with fetal growth restriction (FGR) which is a failure of the fetus to reach its own growth potential. Activator protein-1 (AP-1) is a family of transcription factors inducible in response to a variety of extracellular stimuli and ...

In eukaryotes, mitochondria are critical for cellular bioenergetics and mediating apoptosis. The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) is an important regulator of mitochondrial biogenesis and function. However, the role of PGC-1alpha in neuronal apoptosis and its regulation by apoptotic pathway are still unknown. We demonstrated that ...

p27 is an atypical tumor suppressor that can regulate the activity of cyclin-dependent kinases and G(0)-to-S phase transitions. More recent studies reveal that p27 may also exhibit its tumor-suppressive function through regulating many other essential cellular events. However, the molecular mechanisms underlying these anticancer effects of p27 are largely unknown. ...

Cell transformation by the v-rel oncogene is mediated by the aberrant expression of genes that are normally tightly regulated by other Rel/NF-kappaB family members. Although a number of genes inappropriately activated or suppressed by v-Rel have been identified, their contributions to the v-Rel transformation process have been poorly characterized. Here, ...

Enhanced expression of the CCN family of secretory integrin-binding proteins correlates with many essential components of the cancerous state, including tumor cell adhesion, proliferation, invasion and migration. Consequently, CCN1 expression is elevated in various cancers, including breast cancer, and its expression directly correlates with poor patient prognosis. Using subtraction-hybridization, combined ...

Growth factor stimulation induces c-Jun-dependent survival of primary endothelial cells. However, the mechanism of c-Jun anti-apoptotic activity has not been identified. We here demonstrate that in response to growth factor treatment, primary human endothelial cells as well as mouse fibroblasts respond with an increased expression of c-Jun that forms a ...

Endoplasmic reticulum (ER) stress-mediated apoptosis is a key feature of hepatocyte cytotoxicity by saturated free fatty acids (FFA). This lipoapoptosis is dependent, in part, on the transcriptional upregulation of the BH3-only protein PUMA (p53 upregulated modulator of apoptosis). Although the activator protein (AP)-1 complex facilitates PUMA expression by saturated FFA, ...

In the ischaemia-reperfused heart, transforming growth factor beta (TGFbeta) proteins trigger the differentiation of cardiac fibroblasts (CFs) contributing to fibrosis. Reoxygenation of the heart, in addition to being a trigger for reperfusion injury, induces tissue remodelling by hyperoxia-sensitive signalling processes involving TGFbeta. Here, we sought to characterize the molecular mechanisms ...

Following stimulation of G protein-coupled receptors (GPCRs) at the cell surface, heterotrimeric G proteins are activated. Both Galpha and Gbetagamma subunits regulate specific effectors to transmit signals received by the receptor. Recent data suggest potential nuclear localization or translocation of the Gbetagamma subunit. Here, we show that co-expression of the ...

Sulfur dioxide (SO(2)) and benzo(a)pyrene (B(a)P) are common industrial and environmental contaminants. However, few data are available on the effects of SO(2) on proto-oncogenes and tumor suppressor genes, as well as the interactions between SO(2) and other xenobiotics regulating proto-oncogenes or tumor suppressor genes expression. To investigate the interactions between ...

The TAF4b subunit of the transcription factor IID, which has a central role in transcription by polymerase II, is involved in promoter recognition by selective recruitment of activators. The activating protein-1 (AP-1) family members participate in oncogenic transformation via gene regulation. Utilizing immunoprecipitation of endogenous protein complexes, we documented specific ...

To understand the involvement of matrix metalloproteinases (MMPs) in 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE)-induced angiogenesis, we have studied the role of MMP-2. 15(S)-HETE induced MMP-2 expression and activity in a time-dependent manner in human dermal microvascular endothelial cells (HDMVECs). Inhibition of MMP-2 activity or depletion of its levels attenuated 15(S)-HETE-induced HDMVEC migration, ...

Jun is essential for fetal development, as fetuses lacking Jun die at mid-gestation with multiple cellular defects in liver and heart. Embryos expressing JunD in place of Jun (Jun(d/d)) can develop to term with normal fetal livers, but display cardiac defects as observed in fetuses lacking Jun. Jun(d/d) mouse embryonic ...

The anticarcinogenic effect of dietary organosulfur compounds has been partly attributed to their modulation of the activity and expression of phase II detoxification enzymes. Our previous studies indicated that garlic allyl sulfides upregulate the expression of the pi class of glutathione S-transferase (GSTP) through the activator protein-1 pathway. Here, we ...

The growing number of biological functions affected by autophagy ascribes a special significance to identification of factors regulating it. The activator protein-1 (AP-1) transcription factors are involved in most aspects of cellular proliferation, death, or survival, yet no information regarding their involvement in autophagy is available. Here, we show that ...

Transient receptor potential melastatin 6 (TRPM6) channel is involved in the reabsorption of magnesium in the kidney. We recently found that TRPM6 expression is up-regulated by EGF, but the regulatory mechanism has not been clear. TRPM6 mRNA was endogenously expressed in HEK293 cells. TRPM6 mRNA expression was increased by EGF, ...

FIAT is a leucine zipper protein whose name was coined for its interaction with ATF4 and subsequent blockage of ATF4-directed osteocalcin gene transcription. FIAT lacks a basic DNA-binding domain but contains three leucine zippers; it heterodimerizes with ATF4 to prohibit binding to DNA. FIAT could also potentially interact with additional ...

Cytochrome P450 2J2 oxidizes arachidonic acid to a series of epoxyeicosatrienoic acid (EET) isomers in human tissues. EETs regulate numerous homeostatic processes, including cytoprotective and proliferative responses against injurious stresses. There is little information currently available on the factors that regulate CYP2J2, but strategies to activate expression could use the ...

p73, the structural and functional homologue of p53, exists as two major forms: the transactivation-proficient, proapoptotic TAp73 or the transactivation-deficient, antiapoptotic DNp73. Expectedly, expression of both these major forms has to be coordinated precisely to achieve the desired cellular outcome. Genotoxic insults resulting in cell death lead to the stabilization ...

Barrier function of the epidermis is maintained by precise expression of keratinocyte-specific structural proteins to form the cornified cell envelope (CE). Loricrin, a major component of the CE, is expressed at the late stage of keratinocyte differentiation. In this study, we reveal the isoform-specific function of protein kinase C (PKC) ...

Transcription factor activator protein-1 (AP-1) super-family is known to modulate expression of array of genes during development of many cancers and considered as an important target for modern therapeutics. But the role of AP-1 during development of human oral cancers is still poorly understood. Because oral cancer is one of ...

Perfluorooctane sulfonate (PFOS) is a persistent and bio-accumulative pollutant ubiquitous in wildlife and humans, which receives many concerns on the fate, transport, distribution, and toxicity. Studies have shown that PFOS-induced neurotoxicity in experimental animals; however, little is known about the potential mechanism of PFOS exposure on the central nervous system ...

This study aims to address if phosphorylation of the transcription factor c-Jun is associated with lesion-induced death of spinal motoneurons, and if this cellular response is modulated by glial-cell-line-derived neurotrophic factor (GDNF). We found that after both distal axotomy and root avulsion, spinal motoneurons in neonatal rats expressed phosphorylated c-Jun ...

Since its discovery more than two decades ago the involvement of the Activating protein 1 (AP-1) in proliferation, inflammation, differentiation, apoptosis, cellular migration and wound healing has been intensively studied. A model based on the early studies suggested antagonistic roles for the Jun proteins in proliferation and transformation. c-Jun was ...

The c-Fos proto-oncogenic transcription factor defines a multigene family controlling many processes both at the cell and the whole organism level. To bind to its target AP-1/12-O-tetradecanoylphorbol-13-acetate-responsive element or cAMP-responsive element DNA sequences in gene promoters and exert its transcriptional part, c-Fos must heterodimerize with other bZip proteins, its best ...