Manganese Superoxide Dismutase mRNA Expression Research Articles

Effects of bamboo leaf extract on energy metabolism, antioxidant capacity, and biogenesis of small intestine mitochondria in broilers.

The present study was carried out to investigate the effects of bamboo leaf extract (BLE) on energy metabolism, antioxidant capacity, and biogenesis of broilers' small intestine mitochondria. A total of 384 one-day-old male Arbor Acres broiler chicks were randomly divided into four groups with six replicates each for 42 d. The control group was fed a basal diet, whereas the BLE1, BLE2, and BLE3 groups consumed basal diets with 1.0, 2.0, and 4.0 g/kg of BLE, respectively. Some markers of mitochondrial energy metabolism including isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, and malate dehydrogenase and some markers of redox system including total superoxide dismutase, malondialdehyde, and glutathione were measured by commercial colorimetric kits. Mitochondrial and cellular antioxidant genes, mitochondrial biogenesis-related genes, and mitochondrial DNA copy number were measured by quantitative real-time-polymerase chain reaction (qRT-PCR). Data were analyzed using the SPSS 19.0, and differences were considered as significant at P < 0.05. BLE supplementation linearly increased jejunal mitochondrial isocitrate dehydrogenase (P < 0.05) and total superoxide dismutase (P < 0.05) activity. The ileal manganese superoxide dismutase mRNA expression was linearly affected by increased dietary BLE supplementation (P < 0.05). Increasing BLE supplementation linearly increased jejunal sirtuin 1 (P < 0.05) and nuclear respiratory factor 1 (P < 0.05) mRNA expression. Linear (P < 0.05) and quadratic (P < 0.05) responses of the ileal nuclear respiratory factor 2 mRNA expression occurred with increased dietary BLE levels. In conclusion, BLE supplementation was beneficial to the energy metabolism, antioxidant capacity, and biogenesis of small intestine mitochondria in broilers. The dose of 4.0 g/kg BLE demonstrated the best effects.

Estrogen Replacement Therapy Induces Antioxidant and Longevity-Related Genes in Women after Medically Induced Menopause.

Females live longer than males in many species, including humans, and estrogens are in part responsible for this protection against aging. We reported previously that estrogens can protect rats against oxidative stress, by inducing antioxidant and longevity-related genes. Thus, this study was aimed at confirming the ability of estrogens to upregulate antioxidant and longevity-related genes in humans. For this purpose, we selected 16 women of reproductive age (18-42 years old) undergoing a fertility treatment that includes a medically induced menopause, at the Valencian Infertility Institute. We took blood samples at each time point of the treatment (basal, induced menopause, estrogen, and estrogen plus progesterone replacement therapy). mRNA expression of antioxidant and longevity-related genes in peripheral blood mononuclear cells (PBMC) was determined by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Determination of reduced glutathione (GSH) in total blood was carried out using high-performance liquid chromatography (HPLC). As expected, we found that medically induced menopause significantly decreased sexual hormone (estrogens and progesterone) levels. It also lowered glutathione peroxidase (GPx), 16S rRNA, P21, and TERF2 mRNA expression and blood GSH levels. Estrogen replacement therapy significantly restored estrogen levels and induced mRNA expression of manganese superoxide dismutase (MnSOD), GPx, 16S rRNA, P53, P21, and TERF2 and restored blood GSH levels. Progesterone replacement therapy induced a significant increase in MnSOD, P53, sestrin 2 (SENS2), and TERF2 mRNA expression when compared to basal conditions. These findings provide evidence for estrogen beneficial effects in upregulating antioxidant and longevity-related genes in women.

Oligopin® Supplementation Mitigates Oxidative Stress in Postmenopausal Women with Osteopenia: A Randomized, Double-blind, Placebo-Controlled Trial

BackgroundEvidence indicates a close association between oxidative stress and the etiopathogenesis of osteopenia. In vitro and animal studies report that Oligopin®, an extract of French maritime pine bark extract, has beneficial effects on oxidative stress. PurposeHere, we aimed to determine whether supplementation with Oligopin® affects bone turnover markers, antioxidant enzymes, and oxidative stress markers in these patients. MethodsForty-three postmenopausal women with osteopenia were randomized in a placebo-controlled, double-blind clinical trial to receive either 150 mg/day Oligopin® (n = 22) or placebo (n = 21) for 12 weeks. Plasma levels of bone turnover markers; osteocalcin (OC), type I collagen cross-linked C-telopeptide (CTX-1), OC/CTX1 ratio along with total antioxidant capacity(TAC), malondialdehyde (MDA) concentration, protein carbonyl, and total thiol contents in plasma, activities of manganese superoxide dismutase (MnSOD) and catalase in both peripheral blood mononuclear cells (PBMCs) and plasma as well as mRNA expression of MnSOD, catalase, and Nrf2 in PBMCs were measured at the baseline and the end of the intervention. ResultsOligopin® supplementation significantly increased OC levels and the ratio of OC to CTX1 in women with osteopenia compared to placebo intervention after 12 weeks. Oligopin® significantly decreased plasma protein carbonyl content in postmenopausal women compared with the after placebo treatment. Moreover, Oligopin® intervention significantly increased plasma total thiol content, TAC, plasma activity of both MnSOD and catalase, and the transcript level of Nrf2, MnSOD, and catalase in comparison with the placebo group. ConclusionSupplementation with 150 mg/day Oligopin® for 12 weeks exerts beneficial effects in postmenopausal osteopenia through improving the antioxidant defense system in the plasma and PBMCs that was accompanied by an increase in indicators of bone turnover.

Role of MnSOD in AIFm2‐Mediated Apoptosis During Cardiac Ischemia/Reperfusion Injury

Role of MnSOD in AIFm2‐Mediated Apoptosis During Cardiac Ischemia/Reperfusion Injury

SENSITIVITY OF BREAST CANCER STEM CELLS (CD24-/CD44+) TO DOXORUBICIN IS ASSOCIATED WITH OXIDATIVE STRESS STATUS

Objective: The aim of this study was to analyze the sensitivity of BCSCs to doxorubicin and its association with oxidative stress.&#x0D; Methods: BCSCs (CD24-/CD44+) were treated with doxorubicin every 2 d for 14 d. The determination of cell viability was performed using a trypan blue exclusion assay. The levels of reactive oxygen species (ROS) were measured using a dihydroethidium (DHE) and a 2’,7’-dichlorofluorescein diacetate (DCFH-DA) probes. Manganese superoxide dismutase (MnSOD) mRNA expression and specific activity were also analyzed. Glutathione (GSH) level was measured using Ellman’s method.&#x0D; Results: The viability of the BCSCs decreased after 2 d of treatment with doxorubicin, but started to increase after 8 d. After 8 d of doxorubicin treatment, the ROS level in the BCSCs decreased, while the MnSOD specific activity increased. In addition, the MnSOD mRNA expression and GSH level were suppressed after 8 d of treatment.&#x0D; Conclusion: Doxorubicin treatment induced cytotoxicity after 2 d by increasing the superoxide levels of the BCSCs. After 8 d of treatment, the sensitivity of BCSCs to doxorubicin decreased due to the suppressed oxidative stress from the enhanced antioxidant activity of the MnSOD.

Reduction in MnSOD promotes the migration and invasion of squamous carcinoma cells.

Reactive oxygen species (ROS) homeostasis is maintained at a higher level in cancer cells, which promotes tumorigenesis. Oxidative stress induced by anticancer drugs may further increase ROS to promote apoptosis, but can also enhance the metastasis of cancer cells. The effects of ROS homeostasis on cancer cells remain to be fully elucidated. In the present study, the effect of a reduction in manganese superoxide dismutase (MnSOD) on the migration and invasion of A431 cells was investigated. Our previous micro-assay data revealed that the mRNA expression of MnSOD was higher in the invasive A431-III cell line compared with that in the parental A431 cell line (A431-P). In the present study, high protein levels of MnSOD and H2O2 production were observed in A431-III cells; however, catalase protein levels were significantly lower in A431-III cells compared with those in the A431-P cell line. The knockdown of MnSOD increased H2O2 levels, enzyme activity, the mRNA levels of matrix metalloproteinase-1, -2 and -9, and the migratory and invasive abilities of the cells. Inducing a reduction in H2O2 using diphenyleneiodonium (DPI) and N-acetyl-l-cysteine decreased the migratory abilities of the cell lines, and DPI attenuated the migratory ability that had been increased by MnSOD small interfering RNA knockdown. Luteolin (Lu) and quercetin (Qu) increased the expression of catalase and reduced H2O2 levels, but without an observed change in the protein levels of MnSOD. Taken together, these data suggest that reduced MnSOD may induce ROS imbalance in cells and promote the metastatic ability of cancer cells. Lu and Qu may attenuate these processes and may be promising potential anticancer agents.

Preventive Effect of Alkaloids from Lotus plumule on Acute Liver Injury in Mice

Lotus plumule is a traditional Chinese food that can be used as a beverage. In this study, three kinds of Lotus plumules from different regions of China were selected to observe the preventive effects of extracted alkaloids on CCl4-induced liver injuries. Animal experiments revealed that alkaloids extracted from Lotus plumules decreased the serum AST (aspartate aminotransferase), ALT (alanine aminotransferase), and TBIL (total bilirubin) levels, enhanced SOD (superoxide dismutase) activity, and reduced MDA (malondialdehyde) level in the liver tissues of mice with liver injury. H&E observation confirmed that alkaloids from Lotus plumules could alleviate CCl4-induced injuries of liver tissues and inhibit the inflammatory effect on hepatocytes. Further qPCR experiments also demonstrated that alkaloids from Lotus plumules upregulated the expression of IκB-α (inhibitor of NF-κB alpha), Cu/Zn-SOD (copper/zinc superoxide dismutase), Mn-SOD (manganese superoxide dismutase), and CAT (catalase) mRNA and downregulated TNF-α (tumor necrosis factor alpha) and NF-κB (nuclear factor kappa B) expression in the liver tissues of mice with liver injury. All three kinds of alkaloids from Lotus plumules could prevent CCl4-induced liver injuries by regulating the levels of oxidative stress and inflammation in mice, and the therapeutic effect was comparable to that of silymarin, the medicine commonly used in the treatment of liver diseases. In summary, alkaloids from Lotus plumules contain bioactive substances with hepatic protective efficacy and possess potential application value in the field of functional food.

Evaluation and prognostic significance of manganese superoxide dismutase in clear cell renal cell carcinoma

The antioxidant enzyme manganese superoxide dismutase (MnSOD) is up-regulated in renal cell carcinoma (RCC) and has been implicated in multiple stages of RCC tumorigenesis and progression. However, the prognostic significance of MnSOD in RCC has not been fully elucidated. This study aimed to investigate the expression profile of MnSOD in clear cell RCC (ccRCC) tissues and evaluate the clinical significance of this enzyme in ccRCC patients. MnSOD mRNA was assessed in 42 ccRCC and 33 normal kidney tissues using the Oncomine database, and its protein was detected in 145 ccRCCs and 3 normal tissues by immunohistochemistry staining. The Oncomine database confirmed higher MnSOD mRNA expression in ccRCC than in normal tissues, and immunohistochemistry analysis revealed that MnSOD protein expression was inversely associated with pathologic grade, clinical stage, tumor size, M status, and cancer-specific survival. In addition, univariate survival analysis demonstrated that high-grade, late-stage, large tumors, stage M1, and low MnSOD expression were associated with a poorer prognosis for cancer-specific survival, and further multivariate analysis revealed that tumor grade, stage, M1 stage, and MnSOD were identified as independent prognostic factors for cancer-specific survival in patients with ccRCC. Collectively, these findings imply that MnSOD is a promising prognostic marker in ccRCC and implies that oxidative stress might be involved in the tumorigenesis and progression of ccRCC.

SUPPRESSION OF MANGANESE SUPEROXIDE DISMUTASE ACTIVITY IN ROTENONE-TREATED HUMAN GLIOBLASTOMA T98G CELLS REDUCES CELL VIABILITY

Objective: Glioma is the most common human primary brain tumor which is highly resistant to oxidative stress-based anticancer. The aim of this study was to analyze the effect of rotenone-induced reactive oxygen species (ROS) on the modulation of manganese superoxide dismutase (MnSOD) expression and cell viability in human glioblastoma (GBM) T98G cells.Methods: In this in vitro experimental study, T98G cells were treated with high-dose rotenone (0.5, 5, and 50 μM, respectively). Following rotenone treatment and intracellular ROS, both peroxide and superoxide radicals were determined. Moreover, we analyzed MnSOD mRNA expression, protein, and specific activity, as well as cell survival including viability, proliferation, apoptosis, and mitochondrial structure.Results: High-dose rotenone treatment of T98G cells significantly increased intracellular ROS and MnSOD mRNA, but its protein and specific activity definitely decreased. The treatment also led to a reduction of cell viability, enhancement of apoptosis, and disruption of mitochondrial integrity.Conclusion: Overproduction of ROS in rotenone-treated human GBM T98G cells could suppress the MnSOD protein level and activity even though mRNA synthesis has been increased. This modulation led to reduced survival of T98G cells through induction of cell death rather than inhibition of cell proliferation.

SUPPRESSION OF MANGANESE SUPEROXIDE DISMUTASE ACTIVITY IN ROTENONE-TREATED HUMAN GLIOBLASTOMA T98G CELLS REDUCES CELL VIABILITY

Objective: Glioma is the most common human primary brain tumor which is highly resistant to oxidative stress-based anticancer. The aim of this study was to analyze the effect of rotenone-induced reactive oxygen species (ROS) on the modulation of manganese superoxide dismutase (MnSOD) expression and cell viability in human glioblastoma (GBM) T98G cells.Methods: In this in vitro experimental study, T98G cells were treated with high-dose rotenone (0.5, 5, and 50 μM, respectively). Following rotenone treatment and intracellular ROS, both peroxide and superoxide radicals were determined. Moreover, we analyzed MnSOD mRNA expression, protein, and specific activity, as well as cell survival including viability, proliferation, apoptosis, and mitochondrial structure.Results: High-dose rotenone treatment of T98G cells significantly increased intracellular ROS and MnSOD mRNA, but its protein and specific activity definitely decreased. The treatment also led to a reduction of cell viability, enhancement of apoptosis, and disruption of mitochondrial integrity.Conclusion: Overproduction of ROS in rotenone-treated human GBM T98G cells could suppress the MnSOD protein level and activity even though mRNA synthesis has been increased. This modulation led to reduced survival of T98G cells through induction of cell death rather than inhibition of cell proliferation.

Maternal dietary manganese protects chick embryos against maternal heat stress via epigenetic-activated antioxidant and anti-apoptotic abilities.

Maternal heat stress induced the aberrant epigenetic patterns resulting in the abnormal development of offspring embryos. It is unclear whether maternal dietary manganese supplementation as an epigenetic modifier could protect the chick embryonic development against maternal heat stress via epigenetic mechanisms. To test this hypothesis using an avian model, a completely randomized design with a 2 (maternal normal and high environmental temperatures of 21 and 32°C, respectively) × 3 (maternal dietary manganese sources, the control diet without manganese supplementation and the control diet + 120 mg/kg as either inorganic or organic manganese) factorial arrangement was adopted. Maternal environmental hyperthermia increased mRNA expressions of heat shock proteins 90 and 70, cyclin-dependent kinase 6 and B-cell CLL/lymphoma 2-associated X protein displaying oxidative damage and apoptosis in the embryonic heart. Maternal environmental hyperthermia impaired the embryonic development associated with the alteration of epigenetic status, as evidenced by global DNA hypomethylation and histone 3 lysine 9 hypoacetylation in the embryonic heart. Maternal dietary manganese supplementation increased the heart anti-apoptotic gene B-cell CLL/lymphoma 2 expressions under maternal environmental hyperthermia and manganese superoxide dismutase enzyme activity in the embryonic heart. Maternal dietary organic Mn supplementation effectively eliminated the impairment of maternal environmental hyperthermia on the embryonic development. Maternal dietary manganese supplementation up-regulated manganese superoxide dismutase mRNA expression by reducing DNA methylation and increasing histone 3 lysine 9 acetylation of its promoter. It is suggested that maternal dietary manganese addition could protect the chick embryonic development against maternal heat stress via enhancing epigenetic-activated antioxidant and anti-apoptotic abilities.

Manganese enhances the expression of the manganese superoxide dismutase in cultured primary chick embryonic myocardial cells

In the present study, the effect of manganese (Mn) on antioxidant status and the expression of the manganese superoxide dismutase (MnSOD) gene in cultured primary myocardial cells collected from the chick embryos was investigated. The hypothesis that Mn supplementation would enhance the expression of MnSOD in cultured primary myocardial cells of chick embryos was tested. Eggs collected from Mn-depleted Arbor Acres laying breeder hens were incubated for 10 days and then myocardial cells were isolated and cultivated for 8 days. The embryonic myocardial cells on day 6 were treated with Mn in the cell culture medium at different time points when the proportion of cells showing spontaneous contraction was over 95% after the 3-day primary culture. A completely randomized design involving a 3 Mn levels (0, 0.5 and 1.0 mmol L−1)×3 incubation time points (12, 24 and 48 h) factorial arrangement of treatments (n=6) was used in the current experiment. The results showed that MnSOD activity and mRNA expression level were induced by Mn and increased with incubation time, which supported the hypothesis that Mn would enhance the expression of the MnSOD gene, and thus might protect myocardial cells from oxidative stress during the chick embryonic development.

Klotho enhances FoxO3-mediated manganese superoxide dismutase expression by negatively regulating PI3K/AKT pathway during tacrolimus-induced oxidative stress

Mammalian members of the forkhead box protein O (FoxO) class of transcription factors are implicated in the regulation of oxidative stress, and FoxO proteins are negatively regulated by the phosphatidylinositol 3-kinase (PI3K)–AKT signaling pathway. We examined the effect of Klotho on the PI3K/AKT pathway and manganese superoxide dismutase (MnSOD) during tacrolimus (Tac)-induced oxidative stress. Klotho-treated mice showed decreased Tac-induced oxidative stress accompanied by functional and histological improvements. Klotho inhibited the PI3K/AKT-mediated phosphorylation of FoxO3a and enhanced FoxO3a binding to the MnSOD promoter. Klotho increased MnSOD mRNA and protein expression in mitochondria. In addition, Klotho reduced Tac-induced mitochondrial dysfunction and decreased mitochondrial reactive oxygen species production, and these effects were enhanced by blocking PI3K activity with LY294002. Collectively, our data showed that Klotho protects Tac-induced oxidative stress by negatively regulating the PI3K/AKT pathway and subsequently enhancing FoxO3a-mediated MnSOD expression.

Effects of 17β-estradiol and 2-methoxyestradiol on the oxidative stress-hypoxia inducible factor-1 pathway in hypoxic pulmonary hypertensive rats.

The present study aimed to investigate the effects of 17β-estradiol (E2) and 2-methoxyestradiol (2ME) on the oxidative stress-hypoxia inducible factor-1 (OS-HIF-1) pathway in hypoxic pulmonary hypertensive rats. Female Sprague-Dawley rats were divided randomly into 4 groups, as follows: i) Control (Group A); ii) ovariectomy (OVX) + hypoxia (Group B); iii) OVX + hypoxia + E2 injection (Group C); and iv) 2ME injection (Group D). The rats were maintained under hypoxic conditions for 8 weeks, and mean pulmonary artery pressure (mPAP) and pulmonary arteriole morphology were measured. The reactive oxygen species, superoxide dismutase (SOD), manganese superoxide dismutase (MnSOD), and copper-zinc superoxide dismutase (Cu/ZnSOD) levels in serum were also measured. MnSOD and HIF-1α expression levels in lung tissue were determined by western blotting and reverse transcription-quantitative polymerase chain reaction. The mPAP and arterial remodeling index were significantly elevated following chronic hypoxia exposure; however, experimental data revealed a reduced response in E2 and 2ME intervention rats. Compared with Group A, Group B had significantly elevated oxidative stress levels, as illustrated by increased serum ROS levels, decreased serum SOD and MnSOD levels and decreased MnSOD mRNA and protein expression levels in lung tissue. Furthermore, HIF-1α mRNA and protein expression in Group B was significantly elevated compared with Group A. E2 and 2ME intervention significantly attenuated the aforementioned parameter changes, suggesting that E2 and 2ME partially ameliorate hypoxic pulmonary hypertension. The underlying mechanism of this may be associated with the increase in MnSOD activity and expression and reduction in ROS level, which reduces the levels of transcription and translation of HIF-1α.

Effects of Resveratrol on Crosstalk between Canonical Β-Catenin/Wnt and FOXO Pathways in Coronary Artery Disease Patients with Metabolic Syndrome: A Case Control Study.

Coronary artery disease (CAD) is the major cause of mortality and morbidity worldwide. The aim of this study was to explore the effect of resveratrol (RES) on Canonical β-catenin/Wnt and forkhead box O (FOXO) pathways in CAD patients. We performed this study on 10 metabolic syndrome patients with three-vessel CAD and 10 sex-aged matched healthy subjects. The effects of RES on β-Catenin, manganese superoxide dismutase (MnSOD), and peroxisome proliferator-activated receptor delta (PPAR-δ) expression were evaluated in peripheral blood mononuclear cells (PBMCs) of participants. RES could increase the MnSOD expression in CAD patients (38%, p < 0.0001). After RES treatment, the MnSOD expression of patients is still non-significantly lower than controls. In both blank and RES treatments, a significant positive correlation between β-catenin and MnSOD mRNA expressions was found in controls, whereas no correlation between these gene expressions was found in untreated PBMCs of CAD patients. However, RES could modestly improve this pathway in CAD. RES could increase the MnSOD activity in healthy and CAD subjects (p = 0.051 and p = 0.009, respectively). Furthermore, in both blank and RES treatments, the significant correlation was found between total β-catenin protein and the MnSOD activity in PBMCs of the controls but not in patients. The cross-talk between β-catenin/Wnt and FOXO pathways was impaired in PBMCs of CAD patients. RES treatment could lead to a modest increase in the MnSOD activity independent of β-catenin/FOXO pathway. Despite a modest improvement in the β-catenin/FOXO pathway after RES treatment, this pathway was not completely repaired in CAD patients.

Evidence for possible role of melatonin in reducing oxidative stress in multiple sclerosis through its effect on SIRT1 and antioxidant enzymes

AimsOxidative stress plays a crucial role in the pathogenesis of multiple sclerosis (MS). Melatonin has a central role in the modulation of oxidative stress pathways. We aimed to investigate the effect of melatonin on mRNA expression and activity of sirtuin1 (SIRT1) and its target genes, manganese superoxide dismutase (MnSOD), and catalase in peripheral blood mononuclear cells (PBMCs) from MS patients and healthy subjects. Key methodsThis study was performed on 12 patients with relapsing–remitting MS (RRMS) and 14 age- and sex-matched healthy subjects. PBMCs were isolated and treated with pharmacological concentration of melatonin (1mM) for 12h. Gene expression was evaluated by real time-PCR. SIRT1 activity in PBMCs was measured using a fluorometric assay. MnSOD and catalase activities in PBMCs were determined by colorimetric assays. Plasma total antioxidant capacity was measured using the ferric reducing ability of plasma assay. Key findingsMelatonin significantly increased activities and mRNA levels of SIRT1 and catalase in both patients and healthy subjects, whereas melatonin treatment caused a pronounced increase in MnSOD mRNA expression and activity only in patients. In MS patients, SIRT1 activity did not correlate with catalase and MnSOD activities before melatonin treatment, while a significant correlation was observed between SIRT1 activity and catalase activity in PBMCs of patients after melatonin treatment. SignificanceIt appears that the antioxidant status is affected in PBMCs from MS patients and melatonin could improve impaired antioxidant defense in MS through upregulation of SIRT1, MnSOD and catalase, which might be important in MS management.

Expression and enzyme activity of MnSOD and catalase in peripheral blood mononuclear cells isolated from multiple sclerosis patients

Background: It is evident that oxidative stress plays a crucial role in etiology of multiple sclerosis (MS). Dysregulation of antioxidant enzymes have been implicated in demylination and neuronal loss in MS. The aim of this study was to evaluate mRNA expression and activity of manganese superoxide dismutase (MnSOD), and catalase in peripheral blood mononuclear cells (PBMCs) from patients with relapsing-remitting multiple sclerosis (RRMS) and healthy controls. Materials and Methods: We recruited 20 RRMS patients and 20 age-and sex-matched healthy subjects. PBMCs were isolated, RNA was extracted and real time-PCR was used to evaluate mRNA expression of MnSOD and catalase. Enzyme activity of MnSOD and catalase were measured using colorimetric assays. Results: We found a significant increase in mRNA expression and activity of catalase in PBMCs from patients compared with controls, which was accompanied by reduced activity and expression of MnSOD in MS patients. Conclusion: It appears that impaired antioxidant enzymes in term of high activity of catalase and decreased activity of MnSOD are involved in MS pathogenesis, however further studies are needed to establish this concept.

Bavachalcone-Induced Manganese Superoxide Dismutase Expression through the AMP-Activated Protein Kinase Pathway in Human Endothelial Cells

Mitochondrial oxidative stress has been suggested as a major etiological factor in cardiovascular diseases. Manganese superoxide dismutase (MnSOD) is an essential antioxidant mitochondrial enzyme. Although polyphenols can induce MnSOD expression, their mechanism of action remains unclear. We examined the effect of bavachalcone, a bioactive compound isolated from Psoralea corylifolia, on MnSOD protein expression and explored whether this effect is mediated through the AMP-activated protein kinase (AMPK) signaling pathway. Our data showed that bavachalcone enhanced the luciferase activity of the MnSOD promoter and increased MnSOD mRNA and protein expressions. Moreover, bavachalcone suppressed the mitochondrial superoxide production in endothelial cells. Conversely, bavachalcone stimulated liver kinase B1 and AMPKα phosphorylation. mRNA interference by using short hairpin RNA (shRNA) of AMPK inhibited bavachalcone-induced MnSOD expression. A-769662, an AMPK activator, also stimulated AMPK activity and increased MnSOD expression. Furthermore, AMPK knockdown by shRNA-AMPK reversed the inhibitory effects of bavachalcone on mitochondrial superoxide production in endothelial cells. These findings indicate that bavachalcone can protect the endothelial function by increasing AMPK activity and MnSOD expression and reducing mitochondrial oxidative stress.

The role of Cu/Zn-SOD and Mn-SOD in the immune response to oxidative stress and pathogen challenge in the clam Meretrix meretrix

The copper/zinc superoxide dismutase (Cu/Zn-SOD) and manganese superoxide dismutase (Mn-SOD) could effectively eliminate reactive oxygen species (ROS) and maintain the redox balance of immune system. In the present study, the potential synergy of Cu/Zn-SOD and Mn-SOD in immune system was investigated in the clam Meretrix meretrix. The expression of Cu/Zn-SOD mainly distributed in hepatopancreas and that of Mn-SOD was higher in gill of M. meretrix, and their mRNA and protein activity paralleled with each other. In response to H2O2 challenge, Cu/Zn-SOD mRNA showed significantly higher level at 24 h post-challenge and Mn-SOD mRNA was significantly higher at 12 and 24 h post-challenge in the experimental clams than in the control clams (P < 0.05). After injection with Vibrio-parahaemolyticus-related bacterium (MM21), the Cu/Zn-SOD mRNA was significantly up-regulated at 24 h and 48 h post-injection and Mn-SOD mRNA was significantly higher at 24 h post-injection in MM21-injected clams than in control clams (P < 0.05), suggesting that both of them might involve in the immune defense to Vibrio challenge. The mRNA expression of Cu/Zn-SOD and Mn-SOD was examined in a Vibrio-resistant population and a control population after MM21 immersion challenge. The increased transcription of Cu/Zn-SOD and Mn-SOD in the resistant population suggested both of them could benefit the immune system to defend against pathogen infection. As expression of Mn-SOD mRNA depended on stimuli and was more easily inducible, its response to H2O2 and Vibrio challenge was earlier than Cu/Zn-SOD. Our study suggested the redox balance might play an important role in M. meretrix to resist pathogen infection.

NiCl2-down-regulated antioxidant enzyme mRNA expression causes oxidative damage in the broiler(')s kidney.

The kidney serves as a major organ of nickel (Ni) excretion and is a target organ for acute Ni toxicity due to Ni accumulation. There are no studies on the Ni or Ni compound-regulated antioxidant enzyme mRNA expression in animals and human beings at present. This study was conducted to investigate the pathway of nickel chloride (NiCl2)-caused renal oxidative damage by the methods of biochemistry, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. Two hundred and eighty one-day-old broilers were randomly divided into four groups and fed on a control diet and three experimental diets supplemented with 300, 600, and 900 mg/kg of NiCl2 for 42 days. Dietary NiCl2 elevated the malondialdehyde (MDA), nitric oxide (NO), 8-hydroxy-2'-deoxyguanosine (8-OHdG) contents, and reduced the ability to inhibit hydroxy radical in the NiCl2-treated groups. Also, the renal inducible nitric oxide synthase (iNOS) activity and mRNA expression levels were increased. The total antioxidant (T-AOC) and activities of antioxidant enzymes including copper zinc superoxide dismutase (CuZn-SOD), manganese superoxide dismutase (Mn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and glutathione-s-transferase (GST) were decreased, and the glutathione (GSH) contents as well were decreased in the kidney. Concurrently, the renal CuZn-SOD, Mn-SOD, CAT, GSH-Px, GST, and GR mRNA expression levels were decreased. The above-mentioned results showed that dietary NiCl2 in excess of 300 mg/kg caused renal oxidative damage by reducing mRNA expression levels and activities of antioxidant enzymes, and then enhancing free radicals generation, lipid peroxidation, and DNA oxidation.