Role of the peroxisome proliferator-activated receptors (PPAR)-α, β/δ and γ triad in regulation of reactive oxygen species signaling in brain

2013 ◽  
Vol 394 (12) ◽  
pp. 1553-1570 ◽  
Author(s):  
Stepan Aleshin ◽  
Georg Reiser
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Brain Diseases ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Oxygen Species ◽  
Overwhelming Evidence ◽  
Wide Range ◽  
Neuroprotective Therapy ◽  
Peroxisome Proliferator Activated Receptors

Abstract Overwhelming evidence shows that oxidative stress is a major cause in development of brain disorders. Low activity of the reactive oxygen species (ROS)-degrading system as well as high levels of oxidative damage markers have been observed in brain tissue of patients with neurodegenerative and other brain diseases to a larger extent than in healthy individuals. Many studies aimed to develop effective and safe antioxidant strategies for the therapy or prevention of brain diseases. Nevertheless, it became clear that rigorous suppression of ROS is deleterious for normal cell functioning. Thus, approaches that can regulate the ROS levels over a wide range, from inhibition to induction, will be a powerful tool for neuroprotection. A most prominent target for such ROS management is the family of peroxisome proliferator-activated receptors (PPARs). All three members (PPAR-α, -β/δ and -γ) of this nuclear receptor subfamily form a tightly connected triad. For individual PPAR isoforms, neuroprotective properties have been well proven. Their involvement in regulation of ROS production and degradation underlies the therapeutic effects. Nevertheless, the current paradigms of the involvement of PPAR in neuroprotective therapy ignore such interconnections of PPARs and aim at antioxidant effects of individual PPAR isoforms, but do not take into account the necessity of careful regulation of ROS levels. The present review (i) summarizes the data, which support the concept of the PPAR triad in brain, (ii) demonstrates that usage of the PPAR triad allows the regulation of PPAR-dependent genes over a wide range, from inhibition to upregulation, and (iii) summarizes the known data concerning the PPAR triad involvement in regulation of ROS. Our report opens new directions in the field of PPAR/ROS-related neuroscience research.

scholarly journals Identification of a Functional Peroxisome Proliferator-Activated Receptor Response Element in the Rat Catalase Promoter

2002 ◽  
Vol 16 (12) ◽  
pp. 2793-2801 ◽  
Author(s):  
Geoffrey D. Girnun ◽  
Frederick E. Domann ◽  
Steven A. Moore ◽  
Mike E. C. Robbins
Keyword(s):  
Reactive Oxygen Species ◽  
Transcription Factors ◽  
Inflammatory Response ◽  
Reactive Oxygen ◽  
Peroxisome Proliferator ◽  
Oxygen Species ◽  
Response Element ◽  
Peroxisome Proliferator Activated Receptor ◽  
Promoter Deletion Analysis

Abstract Peroxisomal proliferator-activated receptor (PPAR)γ has been shown to decrease the inflammatory response via transrepression of proinflammatory transcription factors. However, the identity of PPARγ responsive genes that decrease the inflammatory response has remained elusive. Because generation of the reactive oxygen species hydrogen peroxide (H2O2) plays a role in the inflammatory process and activation of proinflammatory transcription factors, we wanted to determine whether the antioxidant enzyme catalase might be a PPARγ target gene. We identified a putative PPAR response element (PPRE) containing the canonical direct repeat 1 motif, AGGTGA-A-AGTTGA, in the rat catalase promoter. In vitro translated PPARγ and retinoic X receptor-α proteins were able to bind to the catalase PPRE. Promoter deletion analysis revealed that the PPRE was functional, and a heterologous promoter construct containing a multimerized catalase PPRE demonstrated that the PPRE was necessary and sufficient for PPARγ-mediated activation. Treatment of microvascular endothelial cells with PPARγ ligands led to increases in catalase mRNA and activity. These results demonstrate that PPARγ can alter catalase expression; this occurs via a PPRE in the rat catalase promoter. Thus, in addition to transrepression of proinflammatory transcription factors, PPARγ may also be modulating catalase expression, and hence down-regulating the inflammatory response via scavenging of reactive oxygen species.

scholarly journals Oxidative Stress Attenuates Lipid Synthesis and Increases Mitochondrial Fatty Acid Oxidation in Hepatoma Cells Infected with Hepatitis C Virus

2015 ◽  
Vol 291 (4) ◽  
pp. 1974-1990 ◽  
Author(s):  
Donna N. Douglas ◽  
Christopher Hao Pu ◽  
Jamie T. Lewis ◽  
Rakesh Bhat ◽  
Anwar Anwar-Mohamed ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Growth Arrest ◽  
Lipid Synthesis ◽  
Reactive Oxygen ◽  
Hcv Infection ◽  
Peroxisome Proliferator ◽  
Oxygen Species ◽  
Peroxisome Proliferator Activated Receptor

Cytopathic effects are currently believed to contribute to hepatitis C virus (HCV)-induced liver injury and are readily observed in Huh7.5 cells infected with the JFH-1 HCV strain, manifesting as apoptosis highly correlated with growth arrest. Reactive oxygen species, which are induced by HCV infection, have recently emerged as activators of AMP-activated protein kinase. The net effect is ATP conservation via on/off switching of metabolic pathways that produce/consume ATP. Depending on the scenario, this can have either pro-survival or pro-apoptotic effects. We demonstrate reactive oxygen species-mediated activation of AMP-activated kinase in Huh7.5 cells during HCV (JFH-1)-induced growth arrest. Metabolic labeling experiments provided direct evidence that lipid synthesis is attenuated, and β-oxidation is enhanced in these cells. A striking increase in nuclear peroxisome proliferator-activated receptor α, which plays a dominant role in the expression of β-oxidation genes after ligand-induced activation, was also observed, and we provide evidence that peroxisome proliferator-activated receptor α is constitutively activated in these cells. The combination of attenuated lipid synthesis and enhanced β-oxidation is not conducive to lipid accumulation, yet cellular lipids still accumulated during this stage of infection. Notably, the serum in the culture media was the only available source for polyunsaturated fatty acids, which were elevated (2-fold) in the infected cells, implicating altered lipid import/export pathways in these cells. This study also provided the first in vivo evidence for enhanced β-oxidation during HCV infection because HCV-infected SCID/Alb-uPA mice accumulated higher plasma ketones while fasting than did control mice. Overall, this study highlights the reprogramming of hepatocellular lipid metabolism and bioenergetics during HCV infection, which are predicted to impact both the HCV life cycle and pathogenesis.

scholarly journals Treatment of Rats With Hypolipidemic Compound Pirinixic Acid Protects Their Hearts Against Ischemic Injury: Are Mitochondrial KATP Channels and Reactive Oxygen Species Involved?

2013 ◽  
pp. 577-584 ◽  
Author(s):  
M. NEMČEKOVÁ ◽  
S. ČARNICKÁ ◽  
M. FERKO ◽  
M. MURÁRIKOVÁ ◽  
V. LEDVÉNYIOVÁ ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Rat Heart ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Katp Channels ◽  
Ros Generation ◽  
Peroxisome Proliferator ◽  
Oxygen Species ◽  
Protective Effects ◽  
Mitochondrial Katp Channels

Hypolipidemic compound pirinixic acid (WY-14643, WY) is known to exert pleiotropic (other than primary) effects, such as activation of peroxisome proliferator-activated receptors (PPAR-α), transcription factors regulating different cardiac functions. Their role in ischemia-reperfusion (I/R) injury and cardioprotection is less clear, although protective effects of PPAR agonists have been documented. This study was designed to explore the effects of WY on the I/R injury in the rat heart and potential mechanisms involved, including mitochondrial KATP channels (mitoKATP) opening and production of reactive oxygen species (ROS). Langendorff-perfused hearts of rats intragastrally treated with WY (3 mg/kg/day) for 5 days and of control animals were subjected to 30-min global ischemia and 2-h reperfusion with or without 15-min perfusion with mitoKATP blocker 5-hydroxydecanoate (5-HD) prior to I/R. Evaluation of the infarct size (IS, TTC staining) served as the main end-point of protection. Lipid peroxidation (a marker of ROS production) was determined by measurement of myocardial concentration of conjugated dienes (CD), whereas protein expression of endothelial NO synthase was analysed by Western blotting. A 2-fold increase in the cardiac protein levels of eNOS after treatment with WY was accompanied by lower post-I/R levels of CD compared with those in the hearts of untreated controls, although WY itself enhanced ROS generation prior to ischemia. IS was reduced by 47 % in the hearts of WY-treated rats (P<0.05), and this effect was reversed by 5-HD. Results suggest that PPAR-α activation may confer protection against lethal I/R injury in the rat heart that involves up-regulation of eNOS, mitoKATP opening and reduced oxidative stress during I/R.

scholarly journals Enhanced astaxanthin production by oxidative stress using methyl viologen as a reactive oxygen species (ROS) reagent in green microalgae Coelastrum sp.

2020 ◽  
Vol 25 (2) ◽  
pp. 95
Author(s):  
Ameerah Tharek ◽  
Shaza Eva Mohamad ◽  
Koji Iwamoto ◽  
Iwane Suzuki ◽  
Hirofumi Hara ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Methyl Viologen ◽  
Antioxidant Properties ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Green Microalgae ◽  
Wide Range ◽  
Astaxanthin Production ◽  
Potential Resource ◽  
Valuable Compounds

Microalgae are known to be a potential resource of high-value metabolites that can be used in the growing field of biotechnology. These metabolites constitute valuable compounds with a wide range of applications that strongly enhance a bio-based economy. Among these metabolites, astaxanthin is considered the most important secondary metabolite, having superior antioxidant properties. For commercial feasibility, microalgae with enhanced astaxanthin production need to be developed. In this study, the tropical green microalgae strain, Coelastrum sp., isolated from the environment in Malaysia, was incubated with methyl viologen, a reactive oxygen species (ROS) reagent that generates superoxide anion radicals (O2-) as an enhancer to improve the accumulation of astaxanthin. The effect of different concentrations of methyl viologen on astaxanthin accumulation was investigated. The results suggested that the supplementation of methyl viologen at low concentration (0.001 mM) was successfully used as a ROS reagent in facilitating and thereby increasing the production of astaxanthin in Coelastrum sp. at a rate 1.3 times higher than in the control.

scholarly journals Atomoxetine produces oxidative stress and alters mitochondrial function in human neuron-like cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Juan Carlos Corona ◽  
Sonia Carreón-Trujillo ◽  
Raquel González-Pérez ◽  
Denise Gómez-Bautista ◽  
Daniela Vázquez-González ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Mitochondrial Function ◽  
Reactive Oxygen ◽  
Therapeutic Effects ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Mitochondrial Mass ◽  
Norepinephrine Reuptake Inhibitor ◽  
Norepinephrine Reuptake

Abstract Atomoxetine (ATX) is a non-stimulant drug used in the treatment of attention-deficit/hyperactivity disorder (ADHD) and is a selective norepinephrine reuptake inhibitor. It has been shown that ATX has additional effects beyond the inhibition of norepinephrine reuptake, affecting several signal transduction pathways and alters gene expression. Here, we study alterations in oxidative stress and mitochondrial function in human differentiated SH-SY5Y cells exposed over a range of concentrations of ATX. We found that the highest concentrations of ATX in neuron-like cells, caused cell death and an increase in cytosolic and mitochondrial reactive oxygen species, and alterations in mitochondrial mass, membrane potential and autophagy. Interestingly, the dose of 10 μM ATX increased mitochondrial mass and decreased autophagy, despite the induction of cytosolic and mitochondrial reactive oxygen species. Thus, ATX has a dual effect depending on the dose used, indicating that ATX produces additional active therapeutic effects on oxidative stress and on mitochondrial function beyond the inhibition of norepinephrine reuptake.

scholarly journals Reactive oxygen species as universal constraints in life-history evolution

2009 ◽  
Vol 276 (1663) ◽  
pp. 1737-1745 ◽  
Author(s):  
Damian K. Dowling ◽  
Leigh W. Simmons
Keyword(s):  
Reactive Oxygen Species ◽  
Life History ◽  
Evolutionary Biology ◽  
Sperm Quality ◽  
Reactive Oxygen ◽  
Life History Evolution ◽  
Oxygen Species ◽  
Trade Offs ◽  
Wide Range ◽  
History Evolution

Evolutionary theory is firmly grounded on the existence of trade-offs between life-history traits, and recent interest has centred on the physiological mechanisms underlying such trade-offs. Several branches of evolutionary biology, particularly those focusing on ageing, immunological and sexual selection theory, have implicated reactive oxygen species (ROS) as profound evolutionary players. ROS are a highly reactive group of oxygen-containing molecules, generated as common by-products of vital oxidative enzyme complexes. Both animals and plants appear to intentionally harness ROS for use as molecular messengers to fulfil a wide range of essential biological processes. However, at high levels, ROS are known to exert very damaging effects through oxidative stress. For these reasons, ROS have been suggested to be important mediators of the cost of reproduction, and of trade-offs between metabolic rate and lifespan, and between immunity, sexual ornamentation and sperm quality. In this review, we integrate the above suggestions into one life-history framework, and review the evidence in support of the contention that ROS production will constitute a primary and universal constraint in life-history evolution.

The Involvement of Reactive Oxygen Species in Polyploidization of the M-07e Human Megakaryocytic Cell Line.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4300-4300
Author(s):  
Serge Côté ◽  
Nathalie Dussault ◽  
Carl Simard
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Line ◽  
Reactive Oxygen ◽  
Cell Types ◽  
Oxygen Species ◽  
Botulin Toxin ◽  
Cellular Processes ◽  
Intracellular Ros ◽  
Wide Range ◽  
Megakaryocytic Cell

Abstract Hematopoietic cells mature in the bone marrow under the control of a diversity of growth factors and the influence of various cell types producing superoxide and other reactive oxygen species (ROS). As ROS may regulate activities of redox-sensitive enzymes implicated in a wide range of cellular processes, we have exposed the human megakaryocytic cell line M-07e to hydrogen peroxide (H2O2) at concentrations that increased intracellular ROS and examined whether expression of the megakaryocytic programme could be enhanced. The growth-factor dependent M-07e cells display surface markers characteristic of both early myeloid progenitors and more committed members of the magakaryocyte (Mk) lineage, such as glycoproteins GPIIb-IIIa (CD41) and GPIb (CD42). H2O2 significantly reduced cell proliferation without affecting viability. After 4 days of exposure to this reagent, expression of the early Mk marker CD41 was 1.2 times higher than that of control cells. Although no change in the expression of the late Mk marker CD42 was detected, exposure to H2O2 was found to increase the incidence of multinucleate cells, polyploidy and abnormal microtubule organising centre numbers. Investigation of this phenomenon on synchronized M-07e cells revealed that H2O2 arrested cytokinesis at a late stage and that some nuclei were still able to incorporate bromodeoxyuridine (BrdU). Cell division was similarly impaired when M-07e cells were either exposed to botulin toxin C3 transferase or Y-27362 inhibitor, suggesting that H2O2 treatments affected members of the Rho family of small GTP-binding proteins and/or their effectors. Together, these findings indicate that endoreplication in Mk may be linked to changes in the cellular redox state of these cells and support the concept that differentiation and polyploidization are independently regulated events.

scholarly journals 15-Deoxy-Δ12-14-Prostaglandin-J2 Induces Hypertrophy and Loss of Contractility in Human Testicular Peritubular Cells: Implications for Human Male Fertility

Endocrinology ◽  
2010 ◽  
Vol 151 (3) ◽  
pp. 1257-1268 ◽  
Author(s):  
C. Schell ◽  
M. Albrecht ◽  
S. Spillner ◽  
C. Mayer ◽  
L. Kunz ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Smooth Muscle ◽  
Cell Size ◽  
Reactive Oxygen ◽  
Peroxisome Proliferator ◽  
Oxygen Species ◽  
Peroxisome Proliferator Activated Receptor ◽  
Human Male ◽  
Peritubular Cells ◽  
Prostaglandin J2

The wall of the seminiferous tubules contains contractile smooth-muscle-like peritubular cells, thought to be important for sperm transport. Impaired spermatogenesis in men typically involves remodeling of this wall, and we now found that smooth muscle cell (SMC) markers, namely myosin heavy chain (MYH11) and smooth muscle actin (SMA) are often lost or diminished in peritubular cells of testes of men with impaired spermatogenesis. This suggests reduced contractility of the peritubular wall, which may contribute to sub- or infertility. In these cases, testicular expression of cyclooxygenase-2 (COX-2) implies formation of prostaglandins (PGs). When screening different PGs for their ability to target human testicular peritubular cells (HTPCs), only a PG metabolite, 15-deoxy-Δ12-14-prostaglandin-J2 (15dPGJ2), was effective. In primary cultures of HTPCs, 15dPGJ2 increased cell size in a reversible manner. Importantly, 15dPGJ2 treatment resulted in a loss of typical differentiation markers for SMCs, namely MYH11, calponin, and SMA, whereas fibroblast markers were unchanged. Collagen gel contraction assays revealed that this loss correlates with a reduced ability to contract. Experiments with an antagonist (bisphenol A diglycidyl ether) and agonist (troglitazone) for a cognate 15dPGJ2 receptor (i.e. peroxisome proliferator-activated receptor-γ) indicated that peroxisome proliferator-activated receptor-γ is not directly involved. Rather, the mode of action of 15dPGJ2 involves reactive oxygen species. The antioxidant N-acetylcysteine not only blocked ROS formation but also prevented the increase in cell size and the loss of contractility in HTPCs challenged with 15dPGJ2. We conclude that 15dPGJ2, via reactive oxygen species, influences SMC phenotype and contractility of human peritubular cells and possibly is involved in the development of human male sub-/infertility.

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