scholarly journals Protective Effects of Salidroside on Mitochondrial Functions against Exertional Heat Stroke-Induced Organ Damage in the Rat

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Wei Zhang ◽  
Ming Peng ◽  
Yang Yang ◽  
Zhangwu Xiao ◽  
Bin Song ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Multiorgan Failure ◽  
Heat Stroke ◽  
Organ Damage ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Protective Effects ◽  
Exertional Heat Stroke ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mitochondrial Functions

Exertional heat stroke (EHS) results in a constellation of systemic inflammatory responses resulting in multiorgan failure and an extremely high mortality. The present study was designed to evaluate the protective effects of salidroside on EHS by improving mitochondrial functions in the rat model. Liver and heart mitochondria were observed by transmission electron microscopy and mitochondrial membrane potential (ΔΨm) was detected by a fluorescent probe. Intramitochondrial free Ca2+concentration, mitochondrial respiratory control ratio (RCR), reactive oxygen species (ROS) levels, superoxide dismutase (SOD), and malondialdehyde (MDA) activity were detected by the corresponding kits. RT-PCR was performed to estimate peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α) and manganese form of SOD (MnSOD) mRNA expression. The results demonstrated that salidroside was able to relieve EHS damage by reducing the swelling of mitochondria, ROS levels, and MDA activity, as well as increasing ΔΨm, RCR, free Ca2+concentration, SOD, PGC-1α, and MnSOD mRNA levels. In conclusion, salidroside has protective effects on mitochondrial functions against exertional heat stroke-induced organ damage in the rat.

scholarly journals BST204 Protects Dexamethasone-Induced Myotube Atrophy through the Upregulation of Myotube Formation and Mitochondrial Function

2021 ◽  
Vol 18 (5) ◽  
pp. 2367
Author(s):  
Ryuni Kim ◽  
Hyebeen Kim ◽  
Minju Im ◽  
Sun Kyu Park ◽  
Hae Jung Han ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Inflammatory Responses ◽  
Mammalian Target Of Rapamycin ◽  
Inhibitory Effect ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Dry Extract ◽  
Myotube Formation ◽  
Species Production

BST204 is a purified ginseng dry extract that has an inhibitory effect on lipopolysaccharide-induced inflammatory responses, but its effect on muscle atrophy is yet to be investigated. In this study, C2C12 myoblasts were induced to differentiate for three days followed by the treatment of dexamethasone (DEX), a corticosteroid drug, with vehicle or BST204 for one day and subjected to immunoblotting, immunocytochemistry, qRT-PCR and biochemical analysis for mitochondrial function. BST204 alleviates the myotube atrophic effect mediated by DEX via the activation of protein kinase B/mammalian target of rapamycin (Akt/mTOR) signaling. Through this pathway, BST204 suppresses the expression of muscle-specific E3 ubiquitin ligases contributing to the enhanced myotube formation and enlarged myotube diameter in DEX-treated myotubes. In addition, BST204 treatment significantly decreases the mitochondrial reactive oxygen species production in DEX-treated myotubes. Furthermore, BST204 improves mitochondrial function by upregulating the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) in DEX-induced myotube atrophy. This study provides a mechanistic insight into the effect of BST204 on DEX-induced myotube atrophy, suggesting that BST204 has protective effects against the toxicity of a corticosteroid drug in muscle and promising potential as a nutraceutical remedy for the treatment of muscle weakness and atrophy.

scholarly journals Attenuation of Colon Inflammation through Activators of the Retinoid X Receptor (Rxr)/Peroxisome Proliferator–Activated Receptor γ (Pparγ) Heterodimer

2001 ◽  
Vol 193 (7) ◽  
pp. 827-838 ◽  
Author(s):  
Pierre Desreumaux ◽  
Laurent Dubuquoy ◽  
Sophie Nutten ◽  
Michel Peuchmaur ◽  
Walter Englaro ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Synergistic Effects ◽  
Survival Rates ◽  
Nuclear Factor Κb ◽  
Retinoid X Receptor ◽  
Trinitrobenzene Sulfonic Acid ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Colon Inflammation

The peroxisome proliferator–activated receptor γ (PPARγ) is highly expressed in the colon mucosa and its activation has been reported to protect against colitis. We studied the involvement of PPARγ and its heterodimeric partner, the retinoid X receptor (RXR) in intestinal inflammatory responses. PPARγ1/− and RXRα1/− mice both displayed a significantly enhanced susceptibility to 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis compared with their wild-type littermates. A role for the RXR/PPARγ heterodimer in the protection against colon inflammation was explored by the use of selective RXR and PPARγ agonists. TNBS-induced colitis was significantly reduced by the administration of both PPARγ and RXR agonists. This beneficial effect was reflected by increased survival rates, an improvement of macroscopic and histologic scores, a decrease in tumor necrosis factor α and interleukin 1β mRNA levels, a diminished myeloperoxidase concentration, and reduction of nuclear factor κB DNA binding activity, c-Jun NH2-terminal kinase, and p38 activities in the colon. When coadministered, a significant synergistic effect of PPARγ and RXR ligands was observed. In combination, these data demonstrate that activation of the RXR/PPARγ heterodimer protects against colon inflammation and suggest that combination therapy with both RXR and PPARγ ligands might hold promise in the clinic due to their synergistic effects.

scholarly journals HMGB1 Is Involved in the Protective Effect of the PPARαAgonist Fenofibrate against Cardiac Hypertrophy

PPAR Research ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Zhankui Jia ◽  
Rui Xue ◽  
Gangqiong Liu ◽  
Ling Li ◽  
Jinjian Yang ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Nuclear Dna ◽  
Inflammatory Responses ◽  
High Mobility ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Inhibitory Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hmgb1 Expression ◽  
Potential Strategy

High mobility group box 1 (HMGB1) is a ubiquitous nuclear DNA-binding protein whose function is dependent on its cellular location. Extracellular HMGB1 is regarded as a delayed mediator of proinflammatory cytokines for initiating and amplifying inflammatory responses, whereas nuclear HMGB1 has been found to prevent cardiac hypertrophy and heart failure. Because fenofibrate, a peroxisome proliferator-activated receptorα(PPARα) agonist, has shown both protective effects against cardiac hypertrophy and inhibitory effects against inflammation, the potential modulation of HMGB1 expression and secretion by fenofibrate is of great interest. We herein provide evidence that fenofibrate modulates basal and LPS-stimulated HMGB1 expression and localization in addition to secretion of HMGB1 in cardiomyocytes. In addition, administration of fenofibrate to mice prevented the development of cardiac hypertrophy induced by thoracic transverse aortic constriction (TAC) while increasing levels of nuclear HMGB1. Altogether, these data suggest that fenofibrate may inhibit the development of cardiac hypertrophy by regulating HMGB1 expression, which provides a new potential strategy to treat cardiac hypertrophy.

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 The 5,7-Dimethoxyflavone Suppresses Sarcopenia by Regulating Protein Turnover and Mitochondria Biogenesis-Related Pathways

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1079 ◽  
Author(s):  
Changhee Kim ◽  
Jae-Kwan Hwang
Keyword(s):  
Muscle Mass ◽  
Protein Turnover ◽  
Inflammatory Responses ◽  
Biological Activities ◽  
Muscle Disease ◽  
Initiation Factor ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Necrosis Factor Alpha ◽  
Peroxisome Proliferator Activated Receptor

Sarcopenia is a muscle disease featured by the loss of muscle mass and dysfunction with advancing age. The 5,7-dimethoxyflavone (DMF), a major flavone found in Kaempferia parviflora, has biological activities, including anti-diabetes, anti-obesity, and anti-inflammation. However, its anti-sarcopenic effect remains to be elucidated. This current study investigated the inhibitory activity of DMF on sarcopenia. Eighteen-month-old mice were orally administered DMF at the dose of 25 mg·kg−1·day−1 or 50 mg·kg−1·day−1 for 8 weeks. DMF not only stimulated grip strength and exercise endurance but also increased muscle mass and volume. Besides, DMF stimulated the phosphatidylinositol 3-kinase-Akt pathway, consequently activating the mammalian target of rapamycin-eukaryotic initiation factor 4E-binding protein 1-70-kDa ribosomal protein S6 kinase pathway for protein synthesis. DMF reduced the mRNA expression of E3 ubiquitin ligase- and autophagy-lysosomal-related genes involved in proteolysis via the phosphorylation of Forkhead box O3. DMF upregulated peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, nuclear respiratory factor 1, and mitochondrial transcription factor A along with the increase of relative mitochondrial DNA content. DMF alleviated inflammatory responses by reducing the tumor necrosis factor-alpha and interleukin-6 serum and mRNA levels. Collectively, DMF can be used as a natural agent to inhibit sarcopenia via improving protein turnover and mitochondria function.

scholarly journals PPARγ in Ischemia-Reperfusion Injury: Overview of the Biology and Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Ruizhen Huang ◽  
Chiyu Zhang ◽  
Xing Wang ◽  
Honglin Hu
Keyword(s):  
Reperfusion Injury ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Tissue Perfusion ◽  
Traumatic Shock ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Promising Therapeutic Target

Ischemia-reperfusion injury (IRI) is a complex pathophysiological process that is often characterized as a blood circulation disorder caused due to various factors (such as traumatic shock, surgery, organ transplantation, burn, and thrombus). Severe metabolic dysregulation and tissue structure destruction are observed upon restoration of blood flow to the ischemic tissue. Theoretically, IRI can occur in various tissues and organs, including the kidney, liver, myocardium, and brain, among others. The advances made in research regarding restoring tissue perfusion in ischemic areas have been inadequate with regard to decreasing the mortality and infarct size associated with IRI. Hence, the clinical treatment of patients with severe IRI remains a thorny issue. Peroxisome proliferator-activated receptor γ (PPARγ) is a member of a superfamily of nuclear transcription factors activated by agonists and is a promising therapeutic target for ameliorating IRI. Therefore, this review focuses on the role of PPARγ in IRI. The protective effects of PPARγ, such as attenuating oxidative stress, inhibiting inflammatory responses, and antagonizing apoptosis, are described, envisaging certain therapeutic perspectives.

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

Immuno ◽  
2022 ◽  
Vol 2 (1) ◽  
pp. 104-117
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 ◽  
Pparγ Agonist ◽  
And Function ◽  
First Time

The 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 knockdown or overexpression of miR-511-3p inversely correlates with PPARγ mRNA levels and affects its transcriptional activity following treatment with rosiglitazone (RSG; PPARγ agonist), in the presence or absence of LPS. Additionally, we show that PPARγ-mediated suppression of DC activation and pro-inflammatory cytokine production in miR-511-3p knockdown DCs is abrogated following overexpression of miR-511-3p. Lastly, PPARγ activation suppressed LPS-mediated induction of indoleamine 2,3-dioxygenase (IDO) activity in DCs, most likely due to changes in miR-511-3p expression. Our data thus suggests 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 A Case of Exertional Heat Stroke Complicated by Hypoxic Hepatitis

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Bertram K. Woitok ◽  
Shawki Bahmad ◽  
Gregor Lindner
Keyword(s):  
Supportive Care ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Multiorgan Failure ◽  
Heat Stroke ◽  
Exertional Heat Stroke ◽  
Hypoxic Hepatitis ◽  
Threatening Condition ◽  
Life Threatening ◽  
Delayed Referral

Background.Exertional heat stroke is a life-threatening condition often complicated by multiorgan failure. We hereby present a case of a 25-year-old male presenting with syncope after a 10  km run in 28°C outside temperature who developed acute liver failure. Case Presentation. Initial temperature was found to be 41.1°C, and cooling measures were rapidly applied. He suffered from acute renal failure and rhabdomyolysis and proceeded to acute liver failure (ASAT 6100 U/l and ALAT 6561 U/l) due to hypoxic hepatitis on day 3. He did not meet criteria for emergency liver transplantation and recovered on supportive care. Conclusions. Acute liver failure due to heat stroke is a life-threatening condition with often delayed onset, which nevertheless resolves on supportive care in the majority of cases; thus, a delayed referral to transplant seems to be reasonable.

scholarly journals Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis

2021 ◽  
Vol 11 (3) ◽  
pp. 325
Author(s):  
Fatima M. Shakova ◽  
Yuliya I. Kirova ◽  
Denis N. Silachev ◽  
Galina A. Romanova ◽  
Sergey G. Morozov
Keyword(s):  
Rat Model ◽  
Nuclear Translocation ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Protein Markers ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pharmacological Agents ◽  
Ischemic Brain ◽  
Neuroprotective Therapy ◽  
Dependent Protein

The pharmacological induction and activation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), a key regulator of ischemic brain tolerance, is a promising direction in neuroprotective therapy. Pharmacological agents with known abilities to modulate cerebral PGC-1α are scarce. This study focused on the potential PGC-1α-modulating activity of Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) and Semax (ACTH(4–7) analog) in a rat model of photochemical-induced thrombosis (PT) in the prefrontal cortex. Mexidol (100 mg/kg) was administered intraperitoneally, and Semax (25 μg/kg) was administered intranasally, for 7 days each. The expression of PGC-1α and PGC-1α-dependent protein markers of mitochondriogenesis, angiogenesis, and synaptogenesis was measured in the penumbra via immunoblotting at Days 1, 3, 7, and 21 after PT. The nuclear content of PGC-1α was measured immunohistochemically. The suppression of PGC-1α expression was observed in the penumbra from 24 h to 21 days following PT and reflected decreases in both the number of neurons and PGC-1α expression in individual neurons. Administration of Mexidol or Semax was associated with preservation of the neuron number and neuronal expression of PGC-1α, stimulation of the nuclear translocation of PGC-1α, and increased contents of protein markers for PGC-1α activation. This study opens new prospects for the pharmacological modulation of PGC-1α in the ischemic brain.

Thyroid hormone is required for the phenotype transitions induced by the pharmacological inhibition of calcineurin in adult soleus muscle of rats

2008 ◽  
Vol 294 (1) ◽  
pp. E69-E77 ◽  
Author(s):  
Nathalie Koulmann ◽  
Lahoucine Bahi ◽  
Florence Ribera ◽  
Hervé Sanchez ◽  
Bernard Serrurier ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Soleus Muscle ◽  
Hormone Deficiency ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Thyroid State ◽  
Novel Approach ◽  
A Subunit ◽  
Calcineurin Inhibition

The present experiment was designed to examine the effects of hypothyroidism and calcineurin inhibition induced by cyclosporin A (CsA) administration on both contractile and metabolic soleus muscle phenotypes, with a novel approach to the signaling pathway controlling mitochondrial biogenesis. Twenty-eight rats were randomly assigned to four groups, normothyroid, hypothyroid, and orally treated with either CsA (25 mg/kg, N-CsA and H-CsA) or vehicle (N-Vh and H-Vh), for 3 wk. Muscle phenotype was estimated by the MHC profile and activities of oxidative and glycolytic enzymes. We measured mRNA levels of the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), the major regulator of mitochondrial content. We also studied the expression of the catalytic A-subunit of calcineurin (CnA) both at protein and transcript levels and mRNA levels of modulatory calcineurin inhibitor proteins (MCIP)-1 and -2, which are differentially regulated by calcineurin activity and thyroid hormone, respectively. CsA-administration induced a slow-to-fast MHC transition limited to the type IIA isoform, which is associated with increased oxidative capacities. Hypothyroidism strongly decreased both the expression of fast MHC isoforms and oxidative capacities. Effects of CsA administration on muscle phenotype were blocked in conditions of thyroid hormone deficiency. Changes in the oxidative profile were strongly related to PGC-1α changes and associated with phosphorylation of p38 MAPK. Calcineurin and MCIPs mRNA levels were decreased by both hypothyroidism and CsA without additive effects. Taken together, these results suggest that adult muscle phenotype is primarily under the control of thyroid state. Physiological levels of thyroid hormone are required for the effects of calcineurin inhibition on slow oxidative muscle phenotype.

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