Search results for "Peroxisome proliferator-activated receptor gamma"
showing 10 items of 39 documents
Mechanisms of action of metformin in type 2 diabetes: Effects on mitochondria and leukocyte-endothelium interactions.
2020
Type 2 diabetes (T2D) is a very prevalent, multisystemic, chronic metabolic disorder closely related to atherosclerosis and cardiovascular diseases. It is characterised by mitochondrial dysfunction and the presence of oxidative stress. Metformin is one of the safest and most effective anti-hyperglycaemic agents currently employed as first-line oral therapy for T2D. It has demonstrated additional beneficial effects, unrelated to its hypoglycaemic action, on weight loss and several diseases, such as cancer, cardiovascular disorders and metabolic diseases, including thyroid diseases. Despite the vast clinical experience gained over several decades of use, the mechanism of action of metformin i…
Intensified mitophagy in skeletal muscle with aging is downregulated by PGC-1alpha overexpression in vivo.
2018
Mitochondrial dysfunction plays an important role in the etiology of age-related muscle atrophy known as sarcopenia. PGC-1α is positioned at the center of crosstalk in regulating mitochondrial quality control, but its role in mitophagy in aged skeletal muscle is currently unclear. The present study investigated the effects of aging and PGC-1α overexpression via in vivo DNA transfection on key mitophagy protein markers, as well as mitochondrial dynamics related proteins, metabolic function and antioxidant capacity in mouse muscle. C57BL/6J mice at the age of 2 mo (young, Y; N = 14) and 24 mo (old, O; N = 14) were transfected in vivo with either PGC-1α DNA (OE, N = 7) or GFP (N = 7) into the …
Clearing Amyloid-β through PPARγ/ApoE Activation by Genistein is a Treatment of Experimental Alzheimer’s Disease
2016
Amyloid-b (Ab) clearance from brain, which is decreased in Alzheimer's disease, is facilitated by apolipoprotein E (ApoE). ApoE is upregulated by activation of the retinoid X receptor moiety of the RXR/PPAR dimeric receptor. As we have previously demonstrated, estrogenic compounds, such as genistein, have antioxidant activity, which can be evidenced by increased expression of manganese superoxide dismutase (MnSOD). Furthermore, genistein is a non-toxic, well-tested, and inexpensive drug that activates PPARg receptor. We isolated and cultured cortical astrocytes from dissected cerebral cortices of neonatal mice (C57BL/6 J). Preincubation with genistein (5 mM) for 24 hours, prior to the addit…
2-Methoxyestradiol Affects Mitochondrial Biogenesis Pathway and Succinate Dehydrogenase Complex Flavoprotein Subunit A in Osteosarcoma Cancer Cells.
2017
Background/aim Dysregulation of mitochondrial pathways is implicated in several diseases, including cancer. Notably, mitochondrial respiration and mitochondrial biogenesis are favored in some invasive cancer cells, such as osteosarcoma. Hence, the aim of the current work was to investigate the effects of 2-methoxyestradiol (2-ME), a potent anticancer agent, on the mitochondrial biogenesis of osteosarcoma cells. Materials and methods Highly metastatic osteosarcoma 143B cells were treated with 2-ME separately or in combination with L-lactate, or with the solvent (non-treated control cells). Protein levels of α-syntrophin and peroxisome proliferator-activated receptor gamma, coactivator 1 alph…
Sex-based differences after a single bout of exercise on PGC1α isoforms in skeletal muscle: A pilot study
2020
To date, there are limited and incomplete data on possible sex-based differences in fiber-types of skeletal muscle and their response to physical exercise. Adult healthy male and female mice completed a single bout of endurance exercise to examine the sex-based differences of the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α), heat shock protein 60 (Hsp60), interleukin 6 (IL-6) expression, as well as the Myosin Heavy Chain (MHC) fiber-type distribution in soleus and extensor digitorum longus (EDL) muscles. Our results showed for the first time that in male soleus, a muscle rich of type IIa fibers, endurance exercise activates specifically genes involved in mito…
Peroxisome proliferator-activated receptor-γ coactivator-1α mediates neuroprotection against excitotoxic brain injury in transgenic mice: role of mit…
2016
Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is a transcriptional coactivator involved in the regulation of mitochondrial biogenesis and cell defense. The functions of PGC-1α in physiology of brain mitochondria are, however, not fully understood. To address this we have studied wild-type and transgenic mice with a two-fold overexpression of PGC-1α in brain neurons. Data showed that the relative number and basal respiration of brain mitochondria were increased in PGC-1α transgenic mice compared with wild-type mitochondria. These changes occurred concomitantly with altered levels of proteins involved in oxidative phosphorylation (OXPHOS) as studied by proteomi…
9-cis-Retinoic acid enhances fatty acid-induced expression of the liver fatty acid-binding protein gene
1997
The role of retinoic acids (RA) on liver fatty acid- binding protein (L-FABP) expression was investigated in the well differentiated FAO rat hepatoma cell line. 9-cis-Retinoic acid (9-ci's-RA) specifically enhanced L-FABP mRNA levels in a time- and dose-dependent manner. The higher induction was found 6 h after addition of 10 -6 M 9-CK-RA in the medium. RA also enhanced further both L-FABP mRNA levels and cytosolic L-FABP protein content induced by oleic acid. The retinoid X receptor (RXR) and the peroxisome proliferator-activated receptor (PPAR), which are known to be activated, respectively, by 9-c/s-RA and long chain fatty acid (LCFA), co-operated to bind specifically the peroxisome prol…
Role of Circulating miRNAs as Biomarkers in Idiopathic Pulmonary Arterial Hypertension: Possible Relevance of miR-23a
2015
Idiopathic pulmonary hypertension (IPAH) is a rare disease characterized by a progressive increase in pulmonary vascular resistance leading to heart failure. MicroRNAs (miRNAs) are small noncoding RNAs that control the expression of genes, including some involved in the progression of IPAH, as studied in animals and lung tissue. These molecules circulate freely in the blood and their expression is associated with the progression of different vascular pathologies. Here, we studied the expression profile of circulating miRNAs in 12 well-characterized IPAH patients using microarrays. We found significant changes in 61 miRNAs, of which the expression of miR23a was correlated with the patients’ …
PGC-1α Induction in Pulmonary Arterial Hypertension
2012
Idiopathic Pulmonary arterial hypertension (IPAH) is characterized by the obstructive remodelling of pulmonary arteries, and a progressive elevation in pulmonary arterial pressure (PAP) with subsequent right-sided heart failure and dead. Hypoxia induces the expression of peroxisome proliferator activated receptorγcoactivator-1α(PGC-1α) which regulates oxidative metabolism and mitochondrial biogenesis. We have analysed the expression of PGC-1α, cytochrome C (CYTC), superoxide dismutase (SOD), the total antioxidant status (TAS) and the activity of glutathione peroxidase (GPX) in blood samples of IPAH patients. Expression of PGC-1αwas detected in IPAH patients but not in healthy volunteers. Th…
Underexpressed Coactivators PGC1α AND SRC1 Impair Hepatocyte Nuclear Factor 4α Function and Promote Dedifferentiation in Human Hepatoma Cells
2006
Hepatocyte nuclear factor 4alpha (HNF4alpha) plays critical roles during liver development and in the transcriptional regulation of many hepatic genes in adult liver. Here we have demonstrated that in human hepatoma HepG2 cells, HNF4alpha is expressed at levels as high as in human liver but its activity on target genes is very low or absent. We have discovered that the low expression of key coactivators (PGC1alpha, SRC1, SRC2, and PCAF) might account for the lack of function of HNF4alpha in HepG2 cells. Among them, PGC1alpha and SRC1 are the two most important HNF4alpha coactivators as revealed by reporter assays with an Apo-CIII promoter construct. Moreover, the expression of these two coa…