scholarly journals Activation of PPARα by Fenofibrate Attenuates the Effect of Local Heart High Dose Irradiation on the Mouse Cardiac Proteome

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1845
Author(s):  
Omid Azimzadeh ◽  
Vikram Subramanian ◽  
Wolfgang Sievert ◽  
Juliane Merl-Pham ◽  
Kateryna Oleksenko ◽  
...  
Keyword(s):  
Cardiac Toxicity ◽  
Mitochondrial Respiratory Chain ◽  
High Dose ◽  
Peroxisome Proliferator ◽  
Label Free ◽  
Peroxisome Proliferator Activated Receptor ◽  
Inflammatory Status ◽  
Metabolic Remodeling ◽  
Radiation Induced ◽  
First Time

Radiation-induced cardiovascular disease is associated with metabolic remodeling in the heart, mainly due to the inactivation of the transcription factor peroxisome proliferator-activated receptor alpha (PPARα), thereby inhibiting lipid metabolic enzymes. The objective of the present study was to investigate the potential protective effect of fenofibrate, a known agonist of PPARα on radiation-induced cardiac toxicity. To this end, we compared, for the first time, the cardiac proteome of fenofibrate- and placebo-treated mice 20 weeks after local heart irradiation (16 Gy) using label-free proteomics. The observations were further validated using immunoblotting, enzyme activity assays, and ELISA. The analysis showed that fenofibrate restored signalling pathways that were negatively affected by irradiation, including lipid metabolism, mitochondrial respiratory chain, redox response, tissue homeostasis, endothelial NO signalling and the inflammatory status. The results presented here indicate that PPARα activation by fenofibrate attenuates the cardiac proteome alterations induced by irradiation. These findings suggest a potential benefit of fenofibrate administration in the prevention of cardiovascular diseases, following radiation exposure.

scholarly journals Protein Kinase A/CREB Signaling Prevents Adriamycin-Induced Podocyte Apoptosis via Upregulation of Mitochondrial Respiratory Chain Complexes

2017 ◽  
Vol 38 (1) ◽  
Author(s):  
Kewei Xie ◽  
Mingli Zhu ◽  
Peng Xiang ◽  
Xiaohuan Chen ◽  
Ayijiaken Kasimumali ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Respiratory Chain ◽  
Mitochondrial Respiratory Chain ◽  
Peroxisome Proliferator ◽  
Respiratory Chain Complexes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Kinase A ◽  
Mitochondrial Respiratory

ABSTRACT Previous work showed that the activation of protein kinase A (PKA) signaling promoted mitochondrial fusion and prevented podocyte apoptosis. The cAMP response element binding protein (CREB) is the main downstream transcription factor of PKA signaling. Here we show that the PKA agonist 8-(4-chlorophenylthio)adenosine 3′,5′-cyclic monophosphate–cyclic AMP (pCPT-cAMP) prevented the production of adriamycin (ADR)-induced reactive oxygen species and apoptosis in podocytes, which were inhibited by CREB RNA interference (RNAi). The activation of PKA enhanced mitochondrial function and prevented the ADR-induced decrease of mitochondrial respiratory chain complex I subunits, NADH-ubiquinone oxidoreductase complex (ND) 1/3/4 genes, and protein expression. Inhibition of CREB expression alleviated pCPT-cAMP-induced ND3, but not the recovery of ND1/4 protein, in ADR-treated podocytes. In addition, CREB RNAi blocked the pCPT-cAMP-induced increase in ATP and the expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1-α). The chromatin immunoprecipitation assay showed enrichment of CREB on PGC1-α and ND3 promoters, suggesting that these promoters are CREB targets. In vivo, both an endogenous cAMP activator (isoproterenol) and pCPT-cAMP decreased the albumin/creatinine ratio in mice with ADR nephropathy, reduced glomerular oxidative stress, and retained Wilm's tumor suppressor gene 1 (WT-1)-positive cells in glomeruli. We conclude that the upregulation of mitochondrial respiratory chain proteins played a partial role in the protection of PKA/CREB signaling.

Effects of prenatal PPAR-γ agonist rosiglitazone exposure on rat hippocampus development in a time-dependent manner: A stereological and histopathological study

2017 ◽  
Vol 37 (8) ◽  
pp. 827-835 ◽  
Author(s):  
D Sağır ◽  
B Eren ◽  
BD Yılmaz ◽  
Z Eren ◽  
ON Keleş ◽  
...  
Keyword(s):  
Pyramidal Cells ◽  
Female Rats ◽  
Morphological Properties ◽  
Histopathological Study ◽  
High Dose ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Pregnant Rats ◽  
Peroxisome Proliferator Activated Receptor ◽  
Insulin Sensitizer

Rosiglitazone is in the thiazolidinedione class of drugs used in the treatment of type 2 diabetes mellitus. It works as an insulin sensitizer by binding to the peroxisome proliferator–activated receptor gamma. We investigated the effects of prenatally administered rosiglitazone on pyramidal cell numbers and morphologies in the hippocampus at postnatal period using histochemical and stereological techniques, congenital morphological properties and the number of offspring in rats. Eighteen female rats were grouped into control (C), low-dose rosiglitazone (LDR) and high-dose rosiglitazone (HDR). LDR pregnant rats received 2 mg/kg/day of rosiglitazone via oral gavage during the first 16 days of the pregnancy. HDR rats received 5 mg/kg/day. The infants were grouped into newborn (NB), 4 week (4 W) and 12 week (12 W). A side from histopathologic and congenital assessments, stereological analyses were performed using the optical fractionator method. Congenital anomaly was not detected in any of the rosiglitazone treatment groups, and their number of offspring was similar to that of the C group. Stereological counts revealed a significant reduction in the number of hippocampal pyramidal cells in the C and LDR groups but not in the HDR group until birth to 12th week. When NB groups were compared, the number of pyramidal cells in the HDRNB group was less than those in the LDRNB and CNB groups. HDR affected apoptosis or the proliferation and maturation of progenitor cells to the pyramidal neuron during neurodevelopment in the hippocampus, whereas LDR did not adversely affect neuronal development and did not cause congenital anomalies.

The nuclear receptor peroxisome proliferator-activated receptor-γ promotes oligodendrocyte differentiation through mechanisms involving mitochondria and oscillatory Ca2+ waves

2013 ◽  
Vol 394 (12) ◽  
pp. 1607-1614 ◽  
Author(s):  
Antonietta Bernardo ◽  
Roberta De Simone ◽  
Chiara De Nuccio ◽  
Sergio Visentin ◽  
Luisa Minghetti
Keyword(s):  
Nuclear Receptor ◽  
Neurological Diseases ◽  
Mitochondrial Respiratory Chain ◽  
Peroxisome Proliferator ◽  
Neuroprotective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Environmental Signals ◽  
Ppar Γ ◽  
Mitochondrial Respiratory Chain Activity ◽  
Respiratory Chain Activity

Abstract Peroxisome proliferator-activated receptor-γ (PPAR-γ) is one of the most studied nuclear receptor since its identification as a target to treat metabolic and neurological diseases. In addition to exerting anti-inflammatory and neuroprotective effects, PPAR-γ agonists, such as the insulin-sensitizing drug pioglitazone, promote the differentiation of oligodendrocytes (OLs), the myelin-forming cells of the central nervous system (CNS). In addition, PPAR-γ agonists increase OL mitochondrial respiratory chain activity and OL’s ability to respond to environmental signals with oscillatory Ca2+ waves. Both OL maturation and oscillatory Ca2+ waves are prevented by the mitochondrial inhibitor rotenone and restored by PPAR-γ agonists, suggesting that PPAR-γ promotes myelination through mechanisms involving mitochondria.

scholarly journals MicroRNA-511-3p mediated modulation of the peroxisome proliferator-activated receptor gamma (PPARγ) controls LPS-induced inflammatory responses in human monocyte derived DCs

2020 ◽  
Author(s):  
Dennis Awuah ◽  
Alisa Ruisinger ◽  
Meshal Alobaid ◽  
Chidimma Mbadugha ◽  
Amir M. Ghaemmaghami
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Human Monocyte ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Inflammatory Cytokine Production ◽  
And Function ◽  
First Time ◽  
Selection Of

AbstractThe peroxisome proliferator activated receptor gamma (PPARγ) is a ligand activated transcription factor expressed in dendritic cells (DCs), where it exerts anti-inflammatory responses against TLR4-induced inflammation. Recently, microRNA-511 (miR-511) has also emerged as a key player in controlling TLR4-mediated signalling, and in regulating the function of DCs. Interestingly, PPARγ has been previously highlighted as a putative target of miR-511 activity; however the link between miR-511 and PPARγ and its influence on human DC function within the context of LPS-induced inflammatory responses is unknown. Using a selection of miR-511-3p-specific inhibitors and mimics, we demonstrate for the first time that up or downregulation of miR-511-3p inversely correlates with PPARγ mRNA levels and transcriptional activity following treatment with PPARγ synthetic agonist rosiglitazone (RSG), in the presence or absence of LPS. Additionally, we show that PPARγ activation with RSG modulates LPS-induced DC activation and downregulates pro-inflammatory cytokine production following downregulation of miR-511-3p. Lastly, PPARγ activation was shown to suppress LPS-mediated induction of indoleamine 2,3-dioxygenase (IDO) activity in DCs, most likely due to changes in miR-511-3p expression. These data suggest that PPARγ-induced modulation of DC phenotype and function is influenced by miR-511-3p expression, which may serve as a potential therapeutic target against inflammatory diseases.

scholarly journals Hyperthyroidism causes cardiac dysfunction by mitochondrial impairment and energy depletion

2013 ◽  
Vol 217 (2) ◽  
pp. 215-228 ◽  
Author(s):  
Sangeeta Maity ◽  
Dipak Kar ◽  
Kakali De ◽  
Vivek Chander ◽  
Arun Bandyopadhyay
Keyword(s):  
Stress Reduction ◽  
Cardiac Dysfunction ◽  
Heart Function ◽  
Peroxisome Proliferator ◽  
Energy Depletion ◽  
Peroxisome Proliferator Activated Receptor ◽  
Progressive Decline ◽  
Metabolic Remodeling ◽  
Initial Improvement

This study elucidates the role of metabolic remodeling in cardiac dysfunction induced by hyperthyroidism. Cardiac hypertrophy, structural remodeling, and expression of the genes associated with fatty acid metabolism were examined in rats treated with triiodothyronine (T3) alone (8 μg/100 g body weight (BW), i.p.) for 15 days or along with a peroxisome proliferator-activated receptor alpha agonist bezafibrate (Bzf; 30 μg/100 g BW, oral) and were found to improve in the Bzf co-treated condition. Ultrastructure of mitochondria was damaged in T3-treated rat heart, which was prevented by Bzf co-administration. Hyperthyroidism-induced oxidative stress, reduction in cytochromecoxidase activity, and myocardial ATP concentration were also significantly checked by Bzf. Heart function studied at different time points during the course of T3treatment shows an initial improvement and then a gradual but progressive decline with time, which is prevented by Bzf co-treatment. In summary, the results demonstrate that hyperthyroidism inflicts structural and functional damage to mitochondria, leading to energy depletion and cardiac dysfunction.

scholarly journals Detection and functional characterisation of the transcription factor peroxisome proliferator-activated receptor gamma in lutein cells

1998 ◽  
Vol 159 (3) ◽  
pp. 429-439 ◽  
Author(s):  
B Lohrke ◽  
T Viergutz ◽  
SK Shahi ◽  
R Pohland ◽  
K Wollenhaupt ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Adipogenic Differentiation ◽  
Functional Change ◽  
High Dose ◽  
Peroxisome Proliferator ◽  
Intact Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Enhanced Production ◽  
Functional Characterisation ◽  
Peroxisome Proliferator Activated Receptors

A prominent functional change during differentiation of lutein cells from follicular thecal and granulosa cells is an enhanced production and secretion of progestins. The regulation of this process is not fully understood but may be associated with the expression of transcription factors which activate genes, products of which are involved in pathways of the cholesterol and lipid metabolism. As peroxisome proliferator-activated receptors (PPARs) play a role in both pathways, we were interested in the expression of PPARgamma, a PPAR form which is involved in adipogenic differentiation. First, we were able to show the expression of PPARgamma in bovine lutein cells (day 12 of the ovarian cycle) at the mRNA and protein level by imaging, flow cytometry and blot analysis, and secondly a role of PPARgamma in the secretion of progesterone. The cells (24 h culture) responded dose dependently by increasing progesterone secretion (up to 1.5-fold of the basal level) to an endogenous ligand of PPARgamma, 15-deoxy-delta12,14 prostaglandin J2 (15-dPGJ2) and to the thiazolidinedione ciglitizone. Aurintricarboxylic acid (ATA) was found to reduce the intracellular PPARgamma level and to promote cell cycle progress, indicating that ATA can be used as a tool for experimental changes of PPARgamma proteins in intact cells and for studying the physiological consequences. The ATA-mediated decrease of PPARgamma was accompanied by reduced progesterone production and a progression of the cell cycle, suggesting a function of PPARgamma in both processes. The response to ATA was abrogated by a high dose (>490 nM) of 15-dPGJ2, suggesting that 15-dPGJ2 exerts its effect on steroidogenic activity via PPARgamma and that the 15-dPGJ2-PPARgamma system plays a role in the maintenance of a differentiated quiescent stage in lutein cells.

scholarly journals Effect of taurine intervention on oleic acid-induced primary hepatocyte steatosis in orange-spotted grouper (Epinephelus coioides)

2021 ◽  
pp. 43-43
Author(s):  
Ruyi Xiao ◽  
Hanmo Feng ◽  
Xingjian Niu ◽  
Fakai Bai ◽  
Jidan Ye
Keyword(s):  
Oleic Acid ◽  
Fatty Acid ◽  
Peroxisome Proliferator ◽  
Epinephelus Coioides ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ampk Signaling ◽  
Hepatocyte Steatosis ◽  
Amp Activated Protein Kinase ◽  
First Time

Examination of the molecular mechanism of taurine regulation of lipid metabolism in fish is limited. In this study, an oleic acid (OA)-induced hepatocyte steatosis model of orange-spotted grouper (Epinephelus coioides) was established for the first time. The model was used to test the effect of taurine on steatosis hepatocytes in Control, High-fat (0.4 mM OA) and Taurine (0.4 mM OA + 2 mM taurine) experimental groups of fish. Hepatocyte samples were subjected to transcriptome analysis. A total of 99634 unigenes was assembled, 69982 unigenes were annotated and 1831 differentially expressed genes (DEGs) in Control vs High-fat group, and 526 DEGs in the High-fat vs Taurine group were identified, of which 824 DEGs (Control vs High-fat) and 237 DEGs (High-fat vs Taurine) were observed to be upregulated, and 1007 DEGs (Control vs High-fat) and 289 DEGs (High-fat vs Taurine) were downregulated after taurine intervention. These genes are involved in peroxisome proliferator-activated receptor (PPAR) and 5' AMP-activated protein kinase (AMPK) signaling pathways, fatty acid elongation, primary bile acid biosynthesis, glycerophospholipid and glycerolipid metabolism. The findings provide new clues in understanding the regulatory role of taurine in lipid and fatty acid metabolism of fish. It is hoped that the obtained results will help in the design of feed formulations to improve grouper growth from the perspective of aquaculture nutrition.

scholarly journals Sea grapes extract improves blood glucose, total cholesterol, and PGC-1α in rats fed on cholesterol- and fat-enriched diet

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 718
Author(s):  
Mury Kuswari ◽  
Fahrul Nurkolis ◽  
Nelly Mayulu ◽  
Faisal Maulana Ibrahim ◽  
Nurpudji Astuti Taslim ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Total Cholesterol ◽  
Unsaturated Fatty Acids ◽  
Blood Cholesterol ◽  
Albino Rats ◽  
High Dose ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Phytochemical Content ◽  
Glucose Levels

Background: Sea grapes or  Caulerpa racemosa have a lot of phytochemical content, especially unsaturated fatty acids that are beneficial for health. This study aims to evaluate the effects of sea grapes extract on blood glucose levels, total cholesterol-, and Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α in male Wistar rats, which were given per-oral (p.o.) cholesterol- and carbohydrates fat-enriched diets (CFED). Methods: Forty male Wistar albino rats weighing between 200 – 250 g were used for this study. Animals were randomly distributed into four groups of ten animals each. Group A served as control (received standard dry pellet diet). Rats in group B were fed on CFED for 4 weeks.  Groups C and D were fed on CFED and were administered 150 and 450 mg/kg of  sea grapes extract (p.o.), respectively. Results: Group C rats indicated a blood glucose reduction and an increase in PGC-1α serum, in comparison to group D (p<0.05). There were no significant differences between group C and D in blood cholesterol reduction (high dose of the extract did not have significant effects) (p=0.222), and both groups had the same effect in lowering total cholesterol in rats. Conclusion: Sea grapes extract is proven to improve blood glucose, total cholesterol, and PGC-1α levels in rats fed with CFED.

Sign in / Sign up

Export Citation Format

Share Document