Catalase Protein Levels Research Articles

The calcineurin antagonist RCAN1-4 is induced by exhaustive exercise in rat skeletal muscle

The aim of this work was to study the regulation of the calcineurin antagonist regulator of calcineurin 1 (RCAN1) in rat skeletal muscles after exhaustive physical exercise, which is a physiological modulator of oxidative stress. Three skeletal muscles, namely extensor digitorum longus (EDL), gastrocnemius, and soleus, were investigated. Exhaustive exercise increased RCAN1-4 protein levels in EDL and gastrocnemius, but not in soleus. Protein oxidation as an index of oxidative stress was increased in EDL and gastrocnemius, but remained unchanged in soleus. However, lipid peroxidation was increased in all three muscles. CuZnSOD and catalase protein levels were increased at 3 h postexercise in soleus, whereas they remained unchanged in EDL and gastrocnemius. Calcineurin enzymatic activity declined in EDL and gastrocnemius but not in soleus, and its protein expression was decreased in all three muscles. The level of PGC1-α protein remained unchanged, whereas the protein expression of the transcription factor NFATc4 was decreased in all three muscles. Adiponectin expression was increased in all three muscles. RCAN1-4 expression in EDL and gastrocnemius muscles was augmented by the oxidative stress generated from exhaustive exercise. We propose that increased RCAN1-4 expression and the signal transduction pathways it regulates represent important components of the physiological adaptation to exercise-induced oxidative stress.

Competitive apnea diving sessions induces an adaptative antioxidant response in mononucleated blood cells.

The aim was evaluating the effects of hypoxia/reoxygenation repetitive episodes during 5days of apnea diving (3-day training/2-day competition) on peripheral blood mononuclear cells (PBMCs) antioxidant defenses, oxidative damage, and plasma xanthine oxidase activity. Blood samples, from seven professional apnea divers, were taken under basal conditions the previous morning to the first training session (pre-diving basal), 4h after ending the competition (4h post-diving) and the following morning (15h after last dive) in basal conditions (post-diving basal). Glucose levels significantly decreased whereas triglycerides increased at 4h post-diving, both returning to basal values at post-diving basal. Glutathione reductase and catalase activity significantly increased after 4h post-diving remaining elevated at post-diving basal. Glutathione peroxidase and superoxide dismutase activities and catalase protein levels progressively increased after diving with significant differences respect to initial values at post-diving basal. No significant differences were observed in circulating PBMCs and oxidative damage markers. Plasma xanthine oxidase activity and nitrite levels, but not the inducible nitric oxide synthetase, significantly increased 4h post-diving, returning to the basal values after 15h. In conclusion, chronic and repetitive episodes of diving apnea during five consecutive days increased plasma xanthine oxidase activity and nitric oxide production which could enhance the signalling role of reactive oxygen and nitrogen species for PBMCs antioxidant adaptation against hypoxia/reoxygenation.

Muscle Oxidative Stress and Gene Expression in Rats Bred for High or Low Voluntary Running

Low physical activity levels have been associated with a more glycolytic skeletal muscle phenotype and impaired endogenous antioxidant stores which can lead to increased oxidative stress and associated pathways which include but are not limited to impaired insulin signaling. PURPOSE: We utilized a unique polygenic model of rats bred for high or low voluntary wheel running (HVR and LVR, respectively) to identify differential oxidative stress and gene expression patterns between LVR and HVR rodents. METHODS: Four groups of 2-month old male Wistar rats were used: 1) low voluntary wheel running (LVR) rats housed without a running wheel (LVR SED; n=7); 2) LVR housed with a running wheel (LVR W/WHEEL; n=7); 3) LVR housed with a running wheel and exercised on the treadmill (5 days/week for 20 min/day at 15.0 m/min) (LVR W/WHEEL+TM; n=7); and 4) high voluntary wheel running (HVR) rats housed with a running wheel (HVR W/WHEEL; n=8). Animals were euthanized five weeks after the start of the experiment and the soleus muscles were excised and used for biochemical analyses. RESULTS: Soleus from LVR W/WHEEL+TM and HVR W/WHEEL had higher protein levels of manganese superoxide dismutase than LVR SED (p<0.05). Also, soleus muscles of HVR W/WHEEL had higher protein levels of catalase than LVR SED and LVR W/WHEEL+TM (p<0.05). Soleus from LVR W/WHEEL, LVR W/WHEEL+TM, and HVR W/WHEEL had significantly less 4HNE (marker of oxidative damage) than LVR SED (p<0.05). Soleus UCP3 mRNA levels were less in LVR W/WHEEL+TM compared to LVR SED and LVR W/WHEEL (p<0.05). No changes were detected in soleus GLUT4 or PGC1a (p>0.05). CONCLUSION: These data suggest that varying forms of physical activity have the capacity to modify soleus mRNA markers of oxidative stress differentially between HVR and LVR rats. Therefore, this distinctive polygenic animal model can be employed in future studies to dissect out differences in transcriptomics and proteomics between selectively bred LVR and HVR rodents.

Hippocampal antioxidative system in mesial temporal lobe epilepsy.

To examine antioxidative system in hippocampi of patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (mTLE-HS). Activity and levels of antioxidative enzymes-catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), manganese superoxide dismutase (MnSOD), and copper-zinc superoxide dismutase (CuZnSOD)-were assessed in hippocampi of nine pharmacoresistant mTLE-HS patients (mean age 37.7±[standard deviation] 6.6years) who underwent amygdalohippocampectomy, and in 10 hippocampi obtained via autopsy from five neurologically intact controls (mean age 34.4±9.0years). Subfield and cellular (neuron/astrocyte) distribution of CAT, GPx, and MnSOD was analyzed in detail using immunohistochemical staining. Sclerotic hippocampi showed drastically increased activity of hydrogen peroxide-removing enzymes, CAT (p<0.001), GPx (p<0.001), and GR (p<0.001), and significantly higher protein levels of CAT (p=0.006), GPx (p=0.040), GR (p=0.024), and MnSOD (p=0.004), compared to controls. CAT immunofluorescence was located mainly in neurons in both controls and HS. Control hippocampi showed GPx staining in blood vessels and CA neurons. In HS, GPx-rich loci, representing bundles of astrocytes, emerged in different hippocampal regions, whereas the number of GPx-positive vessels was drastically decreased. Neurons with abnormal morphology and strong MnSOD immunofluorescence were present in all neuronal layers in HS. Small autofluorescent deposits, most likely lipofuscin, were observed, along with astrogliosis, in CA1 in HS. Antioxidative system is upregulated in HS. This documents, for the first time, that epileptogenic hippocampi are exposed to oxidative stress. Our findings provide a basis for understanding the potential involvement of redox alterations in the pathology of epilepsy, and may open new pharmacologic perspectives for mTLE-HS treatment.

Effect of acute intradialytic strength physical exercise on oxidative stress and inflammatory responses in hemodialysis patients

BackgroundOxidative stress and inflammation are common findings in chronic kidney disease (CKD) patients, and they are directly related to the increased risk of developing cardiovascular disease, which is the major cause of death in these patients, particularly for those undergoing hemodialysis (HD). Strength physical exercise is a new therapeutic approach to reduce these complications in CKD patients. Following this, the purpose of this study was to assess the effect of acute intradialytic strength physical exercise on oxidative stress and inflammatory responses in HD patients. MethodsSixteen HD patients were studied (11 women; 44.4±14.6 years; body mass index 23.3±4.9kg/m2; 61.6±43.1 months of dialysis) and served as their own controls. Acute (single session) intradialytic physical exercise were performed at 60% of the one-repetition maximum test for three sets of 10 repetitions for four exercise categories in both lower limbs during 30 minutes. Blood samples were collected on two different days at exactly the same time (30 minutes and 60 minutes after initiating the dialysis—with and without exercise). Antioxidant enzymes activity [superoxide dismutase (SOD), catalase, and glutathione peroxidase], lipid peroxidation marker levels (malondialdehyde), and inflammatory marker levels (high-sensitivity C-reactive protein) were determined. ResultsSOD plasma levels were significantly reduced after acute physical exercise from 244.8±40.7U/mL to 222.4±28.9U/mL (P=0.03) and, by contrast, increased on the day without exercise (218.2±26.5U/mL to 239.4±38.6U/mL, P=0.02). There was no alteration in plasma catalase, glutathione peroxidase, malondialdehyde, or high-sensitivity C-reactive protein levels in on either day (with or without exercise). Additionally, there was no association between these markers and clinical, anthropometric, or biochemical parameters. ConclusionThese data suggest that acute intradialytic strength physical exercise was unable to reduce oxidative stress and inflammation, and in addition, it seems to reduce plasma SOD levels, which could exacerbate the oxidative stress in HD patients.

Sex-based differential regulation of oxidative stress in the vasculature by nitric oxide

BackgroundNitric oxide (•NO) is more effective at inhibiting neointimal hyperplasia following arterial injury in male versus female rodents, though the etiology is unclear. Given that superoxide (O2•−) regulates cellular proliferation, and •NO regulates superoxide dismutase-1 (SOD-1) in the vasculature, we hypothesized that •NO differentially regulates SOD-1 based on sex. Materials and methodsMale and female vascular smooth muscle cells (VSMC) were harvested from the aortae of Sprague-Dawley rats. O2•− levels were quantified by electron paramagnetic resonance (EPR) and HPLC. sod-1 gene expression was assayed by qPCR. SOD-1, SOD-2, and catalase protein levels were detected by Western blot. SOD-1 activity was measured via colorimetric assay. The rat carotid artery injury model was performed on Sprague-Dawley rats ±•NO treatment and SOD-1 protein levels were examined by Western blot. ResultsIn vitro, male VSMC have higher O2•− levels and lower SOD − 1 activity at baseline compared to female VSMC (P < 0.05). •NO decreased O2•− levels and increased SOD − 1 activity in male (P<0.05) but not female VSMC. •NO also increased sod− 1 gene expression and SOD − 1 protein levels in male (P<0.05) but not female VSMC. In vivo, SOD-1 levels were 3.7-fold higher in female versus male carotid arteries at baseline. After injury, SOD-1 levels decreased in both sexes, but •NO increased SOD-1 levels 3-fold above controls in males, but returned to baseline in females. ConclusionsOur results provide evidence that regulation of the redox environment at baseline and following exposure to •NO is sex-dependent in the vasculature. These data suggest that sex-based differential redox regulation may be one mechanism by which •NO is more effective at inhibiting neointimal hyperplasia in male versus female rodents.

Changes in muscle proteomics in the course of the Caudwell Research Expedition to Mt. Everest.

This study employed differential proteomic and immunoassay techniques to elucidate the biochemical mechanisms utilized by human muscle (vastus lateralis) in response to high altitude hypoxia exposure. Two groups of subjects, participating in a medical research expedition (A, n = 5, 19 d at 5300 m altitude; B, n = 6, 66 d up to 8848 m) underwent a ≈ 30% drop of muscular creatine kinase and of glycolytic enzymes abundance. Protein abundance of most enzymes of the tricarboxylic acid cycle and oxidative phosphorylation was reduced both in A and, particularly, in B. Restriction of α-ketoglutarate toward succinyl-CoA resulted in increased prolyl hydroxylase 2 and glutamine synthetase. Both A and B were characterized by a reduction of elongation factor 2 alpha, controlling protein translation, and by an increase of heat shock cognate 71 kDa protein involved in chaperone-mediated autophagy. Increased protein levels of catalase and biliverdin reductase occurred in A alongside a decrement of voltage-dependent anion channels 1 and 2 and of myosin-binding protein C, suggesting damage to the sarcomeric structures. This study suggests that during acclimatization to hypobaric hypoxia the muscle behaves as a producer of substrates activating a metabolic reprogramming able to support anaplerotically the tricarboxylic acid cycle, to control protein translation, to prevent energy expenditure and to activate chaperone-mediated autophagy.

Angiotensin II induces mitochondrial oxidative stress and mtDNA damage in osteoblasts by inhibiting SIRT1–FoxO3a–MnSOD pathway

Previous report showed that angiotensin II accelerates osteoporosis, and recent clinical studies suggest that several antihypertensive drugs, especially angiotensin-converting enzyme inhibitors, reduced bone fractures. However, the underling mechanism by which angiotensin II induces bone dysfunction is largely unknown. Here in this study, we show that angiotensin II induces mitochondrial oxidative stress and mitochondrial DNA (mtDNA) damage. We find that the protein and RNA levels of mitochondrial catalase and manganese superoxide dismutase (MnSOD) are decreased in osteoblasts in the presence of angiotensin II. Further, we show that angiotensin II inhibits the protein level of SIRT1, but not SIRT3, which results in the hyperacetylation of the forkhead box O3a (FoxO3a) and inhibition of the expression of catalase and MnSOD. Finally, we show that SRT3025 (Sirt1 activator) and Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP, a MnSOD mimetics) can markedly reduce mitochondrial oxidative stress and mtDNA damage. In summary, we identify a novel SIRT1–FoxO3a–MnSOD axis in angiotensin II-induced mitochondrial oxidative stress and mtDNA damage in osteoblasts.

Hyperaggregability and impaired nitric oxide production in platelets from postmenopausal women

ObjectiveCardiovascular mortality increases after menopause in women. Nitric oxide is essential for proper platelet function inhibiting its aggregation and maintaining vascular haemostasis. Here, we investigated whether platelet function and intraplatelet l-arginine–nitric oxide pathway are impaired in postmenopausal women. Study designCross-sectional. Main outcomes measuresBlood was collected from 16 premenopausal and 12 postmenopausal women without any additional risk factor for cardiovascular disease. Platelet reactivity was measured by light transmission aggregometry. l-Arginine–nitric oxide pathway was assessed measuring transmembrane l-[3H]-arginine transport, nitric oxide synthase activity by the citrulline assay, and arginase activity by the conversion of l-[14C]arginine to l-[14C]-urea. The activity of antioxidant enzymes was measured by spectrophotometric assays. Protein expression was determined by Western blotting. ResultsPlatelet aggregation was increased in postmenopausal compared to premenopausal women. Postmenopausal women demonstrated reduced plasma levels of l-arginine, a lower nitric oxide synthase activity, similar endothelial and inducible nitric oxide synthase expression, and a compensatory increase in l-arginine transmembrane transport. Arginase expression and activity did not differ between groups. In regard to oxidative stress, no differences between groups were observed NAPDH oxidase subunits expression and protein carbonylation. However, the activity of the antioxidant enzyme superoxide dismutase and catalase protein levels in platelets were higher in postmenopausal women. ConclusionPostmenopausal women present increased platelet reactivity, which may be due to a reduction in intraplatelet nitric oxide synthesis. Platelet hyperaggregability is known to be associated with arterial and venous thromboembolic event; therefore, it may contribute to the heightened risk of cardiovascular adverse events in this population.

Arginase and C-reactive protein as potential serum-based biomarker of head and neck squamous cell carcinoma patients of north east India

Head and neck squamous cell carcinoma (HNSCC) diagnosis involves histopathological investigations with intervention procedures. Widely accepted biochemical panels for HNSCC detection is not available yet. We tried to find out the effectiveness of the serum-based biochemical markers for their prognostic significance in HNSCC. We collected fresh blood samples of 80 HNSCC patients and 100 healthy subjects. Samples were analyzed for absolute levels of arginase (ARG), ornithine aminotransferase (OAT), catalase (CAT), lactate dehydrogenase (LDH), amylase (AMY) activity, and C-reactive protein (CRP). Receiver-operator characteristic curves and Fagan's nomograms were generated. Out of six parameters studied, four (OAT, CAT, LDH, and AMY) did not show biologically significant differences to be used as biomarkers. Significant elevation in serum ARG and CRP levels were observed in HNSCC. The individual estimation of ARG and CRP showed lower specificity, but their combination improved the specificity level to 95%. Our results suggest that serum ARG and CRP together can efficiently diagnose HNSCC.

Involvement of catalase in the protective benefits of metformin in mice with oxidative liver injury

Metformin is a commonly used anti-diabetic drug with AMP-activated protein kinase (AMPK)-dependent hypoglycemic activities. Recent studies have revealed its anti-inflammatory and anti-oxidative properties. In the present study, the anti-oxidative potential of metformin and its potential mechanisms were investigated in a mouse model with carbon tetrachloride (CCl4)-induced severe oxidative liver injury. Our results showed that treatment with metformin significantly attenuated CCl4-induced elevation of serum aminotransferases and hepatic histological abnormalities. The alleviated liver injury was associated with decreased hepatic contents of oxidized glutathione (GSSG) and malondialdehyde (MDA). In addition, metformin treatment dose-dependently enhanced the activities of catalase (CAT) and decreased CCl4-induced elevation of hepatic H2O2 levels, but it had no obvious effects on the protein level of CAT. We also found that metformin increased the level of phosphorylated AMP-activated protein kinase (AMPK), but treatment with AMPK activator AICAR had no obvious effects on CAT activity. A molecular docking analysis indicated that metformin might interact with CAT via hydrogen bonds. These data suggested that metformin effectively alleviated CCl4-induced oxidative liver injury in mice and these hepatoprotective effects might be associated with CAT.

The Effect of L-carnitine on Amethopterin-induced Toxicity in Rat Large Intestine

Background: Amethopterin is a folic acid antagonist which used as a chemotherapeutic agent and its anti-oxidant activity is used to treat many cancer types. This study aimed to determine the possible protective effects of L-carnitine against Amethopterin induced large intestine toxicity. Methodology: A total 60 male albino rats were equally divided into six groups; the first and second groups were the control and L-carnitine groups respectively while the 3rd group was Amethopterin rat group; the 4th and 5th groups were co- and post- treated Amethopterin rat with L-carnitine respectively and the 6th group was self treated Amethopterin rat group. Results: Glutathione, catalase and total protein levels in Amethopterin and self-treated groups showed a significant decrease when compared with control group, while MDA levels in Amethopterin and self-treated groups showed a significant increase when compared with control group. Many of abnormalities as colonic epithelial cell damage in the form of epithelial separation, cellular loss, congestion of blood vessels, crypt hyperplasia and focal depletion of goblet cells were detected in large intestine tissues in Amethopterin rat group (Amethopterin and self-treated groups). A significant increase of the apoptotic protein p53 and a significant decrease in the antiapoptotic Bc1-2 proteins after Amethopterin injection when compared with control group was observed. Conclusions: Treatment (Co- and post-) with L-carnitine were improved the biochemical, histopathological and immunohistochemical alterations in large intestine that treated with Amethopterin.

Cardioprotective effects of angiotensin III against ischemic injury via the AT2 receptor and KATP channels

Angiotensin III (Ang III) has similar effects on blood pressure and aldosterone secretion as Ang II, but cardioprotective effects are also proposed. In this study, we investigated whether Ang III protects the heart against ischemia/reperfusion (I/R) injury. After sacrificing Sprague-Dawley rats, the hearts were perfused with Krebs–Henseleit buffer for a 20 min preischemic period with and without Ang III followed by 20-min global ischemia and 50-min reperfusion. Pretreatment with Ang III (1 μmol/L) improved an increased postischemic left ventricular end-diastolic pressure (LVEDP) and a decreased postischemic left ventricular developed pressure (LVDP) induced by reperfusion compared to untreated hearts. Ang III markedly decreased infarct size and lactate dehydrogenase levels in effluent during reperfusion. Ang III increased coronary flow and the concentrations of atrial natriuretic peptide in coronary effluent during reperfusion. Pretreatment with Ang II type 2 receptor (AT2R) antagonist or ATP-sensitive K+ channel (KATP) blocker for 15 min before ischemia attenuated the improvement of LVEDP, LVDP, and ±dP/dt induced by Ang III. Ang III treatment increased Mn-superoxide dismutase, catalase, and heme oxygenase-1 protein levels, which was attenuated by pretreatment with AT2R antagonist or KATP blocker. Ang III treatment also decreased Bax, caspase-3, and caspase-9 protein levels, and increased Bcl-2 protein level, which were attenuated by pretreatment with AT2R antagonist or KATP blocker. These results suggest that the cardioprotective effects of Ang III against I/R injury may be partly related to activating antioxidant and antiapoptotic enzymes via AT2R and KATP channels.

Triiodothyronine induces lipid oxidation and mitochondrial biogenesis in rat Harderian gland

The rat Harderian gland (HG) is an orbital gland producing a copious lipid secretion. Recent studies indicate that its secretory activity is regulated by thyroid hormones. In this study, we found that both isoforms of the thyroid hormone receptor (Trα (Thra) and Trβ (Thrb)) are expressed in rat HGs. Although Thra is expressed at a higher level, only Thrb is regulated by triiodothyronine (T3). Because T3 induces an increase in lipid metabolism in rat HGs, we investigated the effects of an animal's thyroid state on the expression levels of carnitine palmitoyltransferase-1A (Cpt1a) and carnitine palmitoyltransferase-1B (Cpt1b) and acyl-CoA oxidase (Acox1) (rate-limiting enzymes in mitochondrial and peroxisomal fatty acid oxidation respectively), as well as on the mitochondrial compartment, thereby correlating mitochondrial activity and biogenesis with morphological analysis. We found that hypothyroidism decreased the expression of Cpt1b and Acox1 mRNA, whereas the administration of T3 to hypothyroid rats increased transcript levels. Respiratory parameters and catalase protein levels provided further evidence that T3 modulates mitochondrial and peroxisomal activities. Furthermore, in hypothyroid rat HGs, the mitochondrial number and their total area decreased with respect to the controls, whereas the average area of the individual mitochondrion did not change. However, the average area of the individual mitochondrion was reduced by ∼50% in hypothyroid T3-treated HGs, and the mitochondrial number and the total area of the mitochondrial compartment increased. The mitochondrial morphometric data correlated well with the molecular results. Indeed, hypothyroid status did not modify the expression of mitochondrial biogenesis genes such as Ppargc1a, Nrf1 and Tfam, whereas T3 treatment increased the expression level of these genes.

Anti-apoptotic proteins and catalase-dependent apoptosis resistance in nickel chloride-transformed human lung epithelial cells

Chronic exposure to nickel compounds is associated with increased incidence of certain types of human cancer, including lung and nasal cancers. Despite intensive investigation, the oncogenic processes remain poorly understood. Apoptosis resistance is a key feature for tumor cells to escape physiological surveillance and acquire growth advantage over normal cells. Although NiCl2 exposure induces transformation of human lung epithelial cells, little information is available with regard to its molecular mechanisms, it is also not clear if the transformed cells are apoptosis resistant and tumorigenic. We explored the apoptosis resistance properties of nickel chloride-transformed human lung epithelial cells and the underlying mechanisms. The results showed that transformed BEAS-2B human lung epithelial cells are resistant to NiCl2-induced apoptosis. They have increased Bcl-2, Bcl-xL and catalase protein levels over the passage matched non-transformed counterparts. The mechanisms of apoptosis resistance are mitochondria-mediated and caspase-dependent. Forced overexpression of Bcl-2, Bcl-xL and catalase proteins reduced NiCl2-induced cell death; siRNA-mediated knockdown of their expression sensitized the cells to nickel-induced apoptosis, suggesting that Bcl-2, Bcl-xl and catalase protein expression plays a critical role in apoptosis resistance. Akt also participates in this process, as its overexpression increases Bcl-xL protein expression levels and attenuates NiCl2-induced apoptosis. Furthermore, transformed cells are tumorigenic in a xenograft model. Together, these results demonstrate that nickel-transformed cells are apoptosis-resistant and tumorigenic. Increased expression of Bcl-2, Bcl-xL and catalase proteins are important mechanisms contributing to transformed cell oncogenic properties.

Myelophil attenuates brain oxidative damage by modulating the hypothalamus-pituitary-adrenal (HPA) axis in a chronic cold-stress mouse model

Ethnopharmacological relevanceMyelophil is composed of Astragali Radix and Salviae Miltiorrhizae Radix, according to the long traditional pharmacological practices, and it has been used for patients with chronic fatigue-associated symptoms including concentration problem or memory loss. Aim of the studyThis study aimed to evaluate the clinical relevance of Myelophil on brain oxidative damage using a chronic cold stress mice model. Material and methodsBalb/c mice were subjected to cold stress (4°C for 4h) six times per week for 2 weeks with or without oral administration of Myelophil (50, 100, or 200mg/kg), or ascorbic acid (50mg/kg). ResultsChronic cold stress induced histopathological hippocampal apoptosis with drastically increased serum levels of total reactive oxygen species and nitric oxide, as well as brain lipid peroxidation levels, protein carbonyl, and caspase-3/7 activity. These alterations were significantly ameliorated by Myelophil treatment. Myelophil administration significantly recovered the depleted glutathione and its enzymes, superoxide dismutase activity, and catalase protein and gene expression levels. Serum levels of corticosterone, dopamine, and adrenaline were notably altered by chronic cold stress but were significantly ameliorated by Myelophil treatment. Myelophil also normalized alterations in tumor necrosis factor-α, interleukin (IL)-1β, and IL-10 gene expression and protein levels. Chronic cold stress up-regulated gene expression levels of phenylethanolamine N-methyltransferase and monoamine oxidase-B, and glucocorticoid receptors in the hypothalamus and hippocampus, respectively, whereas Myelophil treatment completely normalized these levels. ConclusionsThese results suggest that Myelophil has potent pharmaceutical effects against chronic cold-stress-induced brain damage by relieving oxidative stress and inflammation and regulating stress hormones in mice.

The biology of hair diversity

Hair diversity, its style, colour, shape and growth pattern is one of our most defining characteristics. The natural versus temporary style is influenced by what happens to our hair during our lifetime, such as genetic hair loss, sudden hair shedding, greying and pathological hair loss in the various forms of alopecia because of genetics, illness or medication. Despite the size and global value of the hair care market, our knowledge of what controls the innate and within-lifetime characteristics of hair diversity remains poorly understood. In the last decade, drivers of knowledge have moved into the arena of genetics where hair traits are obvious and measurable and genetic polymorphisms are being found that raise valuable questions about the biology of hair growth. The recent discovery that the gene for trichohyalin contributes to hair shape comes as no surprise to the hair biologists who have believed for 100years that hair shape is linked to the structure and function of the inner root sheath. Further conundrums awaiting elucidation include the polymorphisms in the androgen receptor (AR) described in male pattern alopecia whose location on the X chromosome places this genetic contributor into the female line. The genetics of female hair loss is less clear with polymorphisms in the AR not associated with female pattern hair loss. Lifestyle choices are also implicated in hair diversity. Greying, which also has a strong genetic component, is often suggested to have a lifestyle (stress) influence and hair follicle melanocytes show declining antioxidant protection with age and lowered resistance to stress. It is likely that hair research will undergo a renaissance on the back of the rising information from genetic studies as well as the latest contributions from the field of epigenetics.

Renoprotective mechanisms of pirfenidone in hypertension-induced renal injury: through anti-fibrotic and anti-oxidative stress pathways

Pirfenidone (PFD) is a novel anti-fibrotic agent that targets TGFβ. However, the mechanisms underlying its renoprotective properties in hypertension-induced renal injury are poorly understood. We investigated the renoprotective properties of PFD and clarified its renoprotective mechanisms in a rat hypertension-induced renal injury model. Dahl salt-sensitive rats were fed a high-salt diet with or without 1% PFD for 6 weeks. During the administration period, we examined the effects of PFD on blood pressure and renal function. After the administration, the protein levels of renal TGFβ, Smad2/3, TNFα, MMP9, TIMP1, and catalase were examined. In addition, total serum antioxidant activity was measured. Compared to untreated rats, PFD treatment significantly attenuated blood pressure and proteinuria. Histological study showed that PFD treatment improved renal fibrosis. PFD may exert its anti-fibrotic effects via the downregulation of TGFβ-Smad2/3 signaling, improvement of MMP9/TIMP1 balance, and suppression of fibroblast proliferation. PFD treatment also increased catalase expression and total serum antioxidant activity. In contrast, PFD treatment did not affect the expression of TNFα protein, macrophage or T-cell infiltration, or plasma interleukin 1β levels. PFD prevents renal injury via its anti-fibrotic and anti-oxidative stress mechanisms. Clarifying the renoprotective mechanisms of PFD will help improve treatment for chronic renal diseases.

Recombinant adenovirus Ad-RUNrf2 reduces paraquat-induced A549 injury

An RU486-inducible recombinant adenovirus-Nrf2 construct (Ad-RUNrf2) was constructed and expressed in H460 cells to determine whether Nrf2 gene expression can be regulated and to observe the effect of the adenovirus Ad-RUNrf2 on inflammatory cytokines, oxidative stress and apoptotic factors that mediate paraquat (PQ)-induced A549 cell injury. The Nrf2 gene within the RU486 (mifepristone)-inducible system was introduced into an adenovirus vector. A549 cells were transfected with Ad-RUNrf2, and Nrf2 expression was detected using Western blotting and real time-polymerase chain reaction (RT-PCR). RT-PCR, Western blots and enzyme-linked immunosorbent assay were used for observing the effect of RU486-induced Nrf2 expression on the inflammatory cytokines (interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α)), oxidative stress factors (catalase (CAT) and malondialdehyde (MDA)) and apoptosis factors (caspase-3, caspase-9 and cytochrome C) that mediated PQ-induced A549 cell injury. After infection of H460 cells by Ad-RUNrf2, RT-PCR and Western blot analyses showed that Nrf2 expression increased with additional RU486 doses. IL-6 and TNF-α protein and gene expression levels were significantly reduced, and IL-10 protein levels were significantly increased. Although IL-10 expression increased, it remained significantly lower than that of noninduced adenovirus infection and the simple virus exposure group. RU486 induced a significant reduction in MDA expression and increased CAT protein levels. Caspase-9 and caspase-3 protein and gene expression levels decreased in the RU486 induction group (p < 0.05). Cytochrome C protein levels were not significantly reduced, but its gene expression was significantly decreased (p < 0.05). Ad-RUNrf2 adenovirus was successfully constructed and can be stably expressed and regulated in cells. Ad-RUNrf2 can reduce PQ-induced inflammation, oxidative stress and apoptosis in A549 cells.

Hesperidin-mediated expression of Nrf2 and upregulation of antioxidant status in senescent rat heart

Oxidative stress is recognized as a key element responsible for the development of age-related pathologies. A declining endogenous defence system during senescence dictates the need for supplementation with exogenous antioxidants through diet. Hesperidin is a naturally occurring flavonone present in citrus fruits and has been shown to have many biological properties, including antioxidant activity. We investigated whether hesperidin supplementation could be valuable in protecting cardiac tissue of aged rats against age-related increase in oxidative stress, as well as the mechanism by which it can boost the antioxidant status of the cell. The activity of antioxidant enzymes, mRNA expression of Nrf2, protein levels of superoxide dismutase and catalase were measured using standard protocols. Hesperidin treatment effectively protected aged rat heart by increasing the activity of enzymic antioxidants. Hesperidin upregulated the protein levels of nuclear factor erythroid 2-related factor 2, which is responsible for maintaining the antioxidant status of the cell. Hesperidin could be useful in protecting cardiomyocytes against age-related increase in oxidative stress mediated by Nrf2 upregulation.