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M Kvandová, M Majzúnová, I Dovinová
The peroxisome proliferator-activated receptors (PPAR) belong to the nuclear superfamily of ligand-activated transcription factors. PPARgamma acts as a nutrient sensor that regulates several homeostatic functions. Its disruption can lead to vascular pathologies, disorders of fatty acid/lipid metabolism and insulin resistance. PPARgamma can modulate several signaling pathways connected with blood pressure regulation. Firstly, it affects the insulin signaling pathway and endothelial dysfunction by modulation of expression and/or phosphorylation of signaling molecules through the PI3K/Akt/eNOS or MAPK/ET-1 pathways...
October 24, 2016: Physiological Research
Aravind T Reddy, Sowmya P Lakshmi, Raju C Reddy
Peroxisome proliferator-activated receptor γ (PPARγ) is now recognized as an important modulator of leukocyte inflammatory responses and function. Its immunoregulatory function has been studied in a variety of contexts, including bacterial infections of the lungs and central nervous system, sepsis, and conditions such as chronic granulomatous disease. Although it is generally believed that PPARγ activation is beneficial for the host during bacterial infections via its anti-inflammatory and antibacterial properties, PPARγ agonists have also been shown to dampen the host immune response and in some cases exacerbate infection by promoting leukocyte apoptosis and interfering with leukocyte migration and infiltration...
2016: PPAR Research
Jiabing Fan, Mian Guo, Choong Sung Im, Joan Pi-Anfruns, Zhong-Kai Cui, Soyon Kim, Benjamin Wu, Tara Aghaloo, Min Lee
Growth factor-based therapeutics using bone morphogenetic protein 2 (BMP-2) present a promising strategy to reconstruct craniofacial bone defects such as mandible. However, clinical applications require supraphysiological BMP doses that often increase inappropriate adipogenesis, resulting in well-documented cyst-like bone formation. Here we reported a novel complementary strategy to enhance osteogenesis and mandibular bone repair by employing small molecule phenamil that has been shown to be a strong activator of BMP signaling...
October 22, 2016: Tissue Engineering. Part A
Jung Seok Hwang, Sun Ah Ham, Taesik Yoo, Won Jin Lee, Kyung Shin Paek, Jae-Hwan Kim, Chi-Ho Lee, Han Geuk Seo
Silent mating type information regulation 2 homolog 1 (SIRT1), a NAD-dependent deacetylase, mediates cellular processes involved in gene silencing and aging. The regulation of lifespan by SIRT1 has been extensively investigated, but less is known about the mechanisms associated with its cellular turnover during inflammatory responses. In this study, we found that peroxisome proliferator-activated receptor (PPAR) γ is associated with SIRT1 stability in murine macrophage RAW 264.7 cells exposed to lipopolysaccharide (LPS)...
October 19, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Ge Shi, Ting-Ting Wang, Juan-Hua Quan, Shi-Jie Li, Man-Feng Zhang, Pei-Yu Liao, Yi-Ming Fan
BACKGROUND: The transcription factor Sox9 is pivotal in the morphogenesis of hair follicles, but its role in sebocytes is poorly understood. OBJECTIVE: We investigated the effect of Sox9 on human sebocyte proliferation, differentiation and lipogenesis. METHODS: Sox9 expression was detected by immunohistochemistry in normal skin and acne lesion. Primary cultured human sebocytes were transfected with adenovirus expressing GFP-Sox9 or Sox9 microRNA...
October 13, 2016: Journal of Dermatological Science
Dong Liu, Jie-Lu Zhou, Fashui Hong, Yu-Qing Zhang
Titanium dioxide nanoparticles (TiO2 NPs) are used in many fields, such as paints, medicine additives, food additives, sunscreens and agriculture. The aim of this study was to investgate the mechanism behind the formation of inflammation induced by TiO2 NPs. ICR mice were exposed to TiO2 NPs through intragastric administration at 2.5, 5 and 10 mg/kg body weight every day for 90 consecutive days. The experiment suggested that long-term exposure to TiO2 NPs resulted in an obvious inflammatory response in mice lung tissues, which led to a thickened alveoli septum, lung hyperaemia, and titanium accumulation...
October 22, 2016: Journal of Biomedical Materials Research. Part A
Yuxin Shu, Yan Lu, Xiaojuan Pang, Wei Zheng, Yahong Huang, Jiahong Li, Jianguo Ji, Can Zhang, Pingping Shen
Peroxisome proliferator-activating receptor γ (PPARγ), a transcription factor, is involved in many important biological processes, including cell terminal differentiation, survival and apoptosis. However, the role of PPARγ, which regulates tumour promoter and oncogene expression, is not well understood in hepatocellular carcinoma (HCC). In the present study, based on evidence from clinical samples that phosphorylation of PPARγ at Ser84 is up-regulated in human liver tumours, we confirmed that phosphorylation of PPARγ was also significantly increased in an HCC mouse model and was increased by Mitogen-activated protein kinase (MEK)/ Extracellular-signal-regulated kinases (ERK) kinase...
October 19, 2016: Oncotarget
Ning Jia, Qinru Sun, Qian Su, Shaokang Dang, Guomin Chen
Substantial evidence has shown that the oxidative damage to hippocampal neurons is associated with the cognitive impairment induced by adverse stimuli during gestation named prenatal stress (PS). Taurine, a conditionally essential amino acid, possesses multiple roles in the brain as a neuromodulator or antioxidant. In this study, to explore the roles of taurine in PS-induced learning and memory impairment, prenatal restraint stress was set up and Morris water maze (MWM) was employed for testing the cognitive function in the one-month-old rat offspring...
October 13, 2016: Redox Biology
Kaitlin Mock, Sundus Lateef, Vagner A Benedito, Janet C Tou
High-fructose corn syrup-55 (HFCS-55) has been suggested to be more lipogenic than sucrose, which increases the risk for nonalcoholic fatty liver disease (NAFLD) and dyslipidemia. The study objectives were to determine the effects of drinking different sugar-sweetened solutions on hepatic gene expression in relation to liver fatty acid composition and risk of NAFLD. Female rats were randomly assigned (n=7 rats/group) to drink water or water sweetened with 13% (w/v) HFCS-55, sucrose or fructose for 8 weeks. Rats drinking HFCS-55 solution had the highest (P=...
September 30, 2016: Journal of Nutritional Biochemistry
Shlomo Sasson
Activated peroxisome proliferator-activated receptor-δ (PPARδ) induces the expression of genes encoding enzymes that metabolize fatty acids and carbohydrate. Attempts to identify cellular activators of PPARδ produced large lists of various fatty acids and their metabolic derivatives; however, there is no consensus on specific and selective binding interactions of natural ligands with PPARδ. Most models on binding interactions within the ligand binding domain (LBD) of PPARδ have been derived from analyses of PPARδ-LBD crystals formed with synthetic low molecular weight ligands...
October 18, 2016: Biochimie
Wei Tuo, Natascha Leleu-Chavain, John Spencer, Supojjanee Sansook, Regis Millet, Philippe Chavatte
Fatty acid ethanolamides (FAEs) and endocannabinoids (ECs) have been shown to alleviate pain and inflammation, regulate motility and appetite, and produce anti-cancer, anxiolytic, and neuroprotective efficacies via cannabinoid receptor type 1 (CB1) or type 2 (CB2), or via peroxisome proliferator-activated receptor α (PPAR-α) stimulation. FAEs and ECs are synthesized by a series of endogenous enzymes, including N-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD), diacylglycerol lipase (DAGL), or phospholipase C (PLC), and their metabolism is mediated by several metabolic enzymes, including fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), N-acylethanolamine acid amidase (NAAA), or cyclooxygenase-2 (COX-2)...
October 21, 2016: Journal of Medicinal Chemistry
Kosuke Kawaguchi, Masashi Morita
ATP-binding cassette (ABC) transporters are one of the largest families of membrane-bound proteins and transport a wide variety of substrates across both extra- and intracellular membranes. They play a critical role in maintaining cellular homeostasis. To date, four ABC transporters belonging to subfamily D have been identified. ABCD1-3 and ABCD4 are localized to peroxisomes and lysosomes, respectively. ABCD1 and ABCD2 are involved in the transport of long and very long chain fatty acids (VLCFA) or their CoA-derivatives into peroxisomes with different substrate specificities, while ABCD3 is involved in the transport of branched chain acyl-CoA into peroxisomes...
2016: BioMed Research International
Min Joo Kim, Young Do Koo, Min Kim, Soo Lim, Young Joo Park, Sung Soo Chung, Hak C Jang, Kyong Soo Park
BACKGROUND: Panax ginseng has glucose-lowering effects, some of which are associated with the improvement in insulin resistance in skeletal muscle. Because mitochondria play a pivotal role in the insulin resistance of skeletal muscle, we investigated the effects of the ginsenoside Rg3, one of the active components of P. ginseng, on mitochondrial function and biogenesis in C2C12 myotubes. METHODS: C2C12 myotubes were treated with Rg3 for 24 hours. Insulin signaling pathway proteins were examined by Western blot...
October 2016: Diabetes & Metabolism Journal
Han-Sol Park, Jung Eun Jang, Myoung Seok Ko, Sung Hoon Woo, Bum Joong Kim, Hyun Sik Kim, Hye Sun Park, In-Sun Park, Eun Hee Koh, Ki-Up Lee
BACKGROUND: Non-alcoholic fatty liver disease is the most common form of chronic liver disease in industrialized countries. Recent studies have highlighted the association between peroxisomal dysfunction and hepatic steatosis. Peroxisomes are intracellular organelles that contribute to several crucial metabolic processes, such as facilitation of mitochondrial fatty acid oxidation (FAO) and removal of reactive oxygen species through catalase or plasmalogen synthesis. Statins are known to prevent hepatic steatosis and non-alcoholic steatohepatitis (NASH), but underlying mechanisms of this prevention are largely unknown...
October 2016: Diabetes & Metabolism Journal
Takayuki Koga, Pei-Li Yao, Maryam Goudarzi, Iain A Murray, Gayathri Balandaram, Frank J Gonzalez, Gary H Perdew, Albert J Fornace, Jeffrey M Peters
Alcoholic liver disease is a pathological condition caused by over-consumption of alcohol. Due to the high morbidity and mortality associated with this disease, there remains a need to elucidate the molecular mechanisms underlying its etiology and to develop new treatments. Since peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) modulates ethanol-induced hepatic effects, the present study examined alterations in gene expression that may contribute to this disease. Chronic ethanol treatment causes increased hepatic CYP2B10 expression in Pparβ/δ+/+ mice, but not in Pparβ/δ-/- mice...
October 20, 2016: Journal of Biological Chemistry
John J Guardiola, Juliane I Beier, K Cameron Falkner, Benjamin Wheeler, Craig James McClain, Matt Cave
BACKGROUND: Occupational vinyl chloride (VC) exposures have been associated with toxicant-associated steatohepatitis and liver cancer. Metabolomics has been used to clarify mode of action in drug-induced liver injury but has not been performed following VC exposures. METHODS: Plasma samples from 17 highly exposed VC workers without liver cancer and 27 unexposed healthy volunteers were obtained for metabolite extraction and GC/MS and LC/MS(2) analysis. Following ion identification/quantification, Ingenuity pathway analysis was performed...
October 17, 2016: Toxicology and Applied Pharmacology
Amalia Pérez-Jiménez, Eva E Rufino-Palomares, Nieves Fernández-Gallego, M Carmen Ortuño-Costela, Fernando J Reyes-Zurita, Juan Peragón, Leticia García-Salguero, Khalida Mokhtari, Pedro P Medina, José A Lupiáñez
BACKGROUND: Metabolic syndrome is a set of pathologies among which stand out the obesity, which is related to the lipid droplet accumulation and changes to cellular morphology regulated by several molecules and transcription factors. Maslinic acid (MA) is a natural product with demonstrated pharmacological functions including anti-inflammation, anti-tumor and anti-oxidation, among others. PURPOSE: Here we report the effects of MA on the adipogenesis process in 3T3-L1 cells...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
H Jęśko, R P Strosznajder
Sirtuins (SIRT1 to -7) are unique histone deacetylases (HDACs) whose activity depends on NAD+, thus making them capable of sensing the cellular metabolic status. Sirtuins orchestrate the stress response and damage repair, and are able to modulate the course of ageing and neurodegenerative diseases. Despite their classification as HDACs, sirtuins deacetylate a vast number of targets in many cellular compartments, and some display additional enzymatic activities including mono(ADP-ribosyl)ation. SIRTs interact with multiple signalling proteins, transcription factors and enzymes including p53, FOXOs (forkhead box subgroup O), PPARs (peroxisome proliferator-activated receptors), NF-B, and DNA-PK (DNA-dependent protein kinase)...
2016: Folia Neuropathologica
Haruta Mogami, Shigeo Yura, Eiji Kondoh, Hiroshi Masutani, Junji Yodoi, Ikuo Konishi
AIM: Thioredoxin binding protein-2 (TBP-2), which is identical to thioredoxin interacting protein (Txnip), controls cellular proliferation and differentiation. The aim of the present study was to compare TBP-2 protein and mRNA expression in human placenta during the three trimesters of pregnancy and to investigate the role of hypoxia in the change of these expressions in placental tissue. A secondary objective was to determine the gene expression of peroxisome proliferator-activated receptors (PPARs) in TBP-2 deficient placenta using TBP-2 gene disrupted mice (TBP-2(-/-) )...
October 20, 2016: Journal of Obstetrics and Gynaecology Research
Ana C Puhl, Paul Webb, Igor Polikarpov
Loss-of-function mutation V290M in the ligand-binding domain of the peroxisome proliferator activated receptor γ (PPARγ) is associated with a ligand resistance syndrome (PLRS), characterized by partial lipodystrophy and severe insulin resistance. In this data article we discuss an X-ray diffraction dataset that yielded the structure of PPARγ LBD V290M mutant refined at 2.3 Å resolution, that allowed building of 3D model of the receptor mutant with high confidence and revealed continuous well-defined electron density for the partial agonist diclofenac bound to hydrophobic pocket of the PPARγ...
June 2016: Data in Brief
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