scholarly journals Neuroprotective Benefits of Exercise and MitoQ on Memory Function, Mitochondrial Dynamics, Oxidative Stress, and Neuroinflammation in D-Galactose-Induced Aging Rats

2021 ◽  
Vol 11 (2) ◽  
pp. 164
Author(s):  
Jae-Hoon Jeong ◽  
Jung-Hoon Koo ◽  
Jang Soo Yook ◽  
Joon-Yong Cho ◽  
Eun-Bum Kang
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Cognitive Impairment ◽  
Nadph Oxidase ◽  
Learning And Memory ◽  
Oxidase Activity ◽  
Mitochondrial Dynamics ◽  
Nadph Oxidase Activity ◽  
Aging Rats ◽  
Positive Effects

Exercise and antioxidants have health benefits that improve cognitive impairment and may act synergistically. In this study, we examined the effects of treadmill exercise (TE) and mitochondria-targeted antioxidant mitoquinone (MitoQ), individually or combined, on learning and memory, mitochondrial dynamics, NADPH oxidase activity, and neuroinflammation and antioxidant activity in the hippocampus of D-galactose-induced aging rats. TE alone and TE combined with MitoQ in aging rats reduced mitochondrial fission factors (Drp1, Fis1) and increased mitochondrial fusion factors (Mfn1, Mfn2, Opa1). These groups also exhibited improved NADPH oxidase activity and antioxidant activity (SOD-2, catalase). TE or MitoQ alone decreased neuroinflammatory response (COX-2, TNF-α), but the suppression was greater with their combination. In addition, aging-increased neuroinflammation in the dentate gyrus was decreased in TE but not MitoQ treatment. Learning and memory tests showed that, contrarily, MitoQ alone demonstrated some similar effects to TE but not a definitive improvement. In conclusion, this study demonstrated that MitoQ exerted some positive effects on aging when used as an isolated treatment, but TE had a more effective role on cognitive impairment, oxidative stress, inflammation, and mitochondria dysfunction. Our findings suggest that the combination of TE and MitoQ exerted no synergistic effects and indicated regular exercise should be the first priority in neuroprotection of age-related cognitive decline.

Abstract 1380: Antioxidants Decrease Neuronal Angiotensin II Type 1 Receptor in Heart Failure: Inhibition of Activator Protein 1 and Jun N-Terminal Kinase

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Dongmei Liu ◽  
Lie Gao ◽  
Kurtis G Cornish ◽  
Irving H Zucker
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Neuronal Cell ◽  
Activator Protein 1 ◽  
Ang Ii ◽  
Nadph Oxidase Activity ◽  
Activator Protein

In a previous study, we showed that Ang II type I receptor (AT1R) expression increased in the rostral ventrolateral medulla (RVLM) of chronic heart failure (CHF) rabbits and in normal rabbits infused with intracerebroventricular (ICV) Angiotensin II (AngII). The present study investigated if oxidative stress plays a role in Ang II induced AT1R upregulation and its relationship to the transcription factor activator protein 1 (AP1) in CHF rabbits and in the CATHa neuronal cell line. In neuronal cell cultures, Ang II significantly increased AT1R mRNA by 153 ± 22%, P <0.01; c-Jun mRNA by 90 ± 10%, P < 0.01; NADPH oxidase activity by 126 ± 43%, P < 0.01 versus untreated cells; Tempol, Apocynin and the AP 1 inhibitor Tanshinone II reversed the increased AT1R, c-Jun expression and NADPH oxidase activity induced by AngII. We examined the effect of ICV Tempol on expression of these proteins in the RVLM of CHF rabbits. Compared to untreated CHF rabbits Tempol significantly decreased AT1R protein expression (0.88±0.16 vs. 1.6±0.29, P <0.05), phosphorylated Jnk protein (0.10±0.02 vs. 0.31±0.10, P <0.05), and phosphorylated c-Jun (0.02±0.001 vs. 0.14±0.05, P <0.05). These data suggest that Ang II induces AT1R upregulation at the transcriptional level by activation of oxidative stress and AP1 in both cultured cells and in intact brain. Antioxidant agents may be beneficial in CHF by decreasing AT1R expression through the Jnk and AP1 pathway.

scholarly journals Protective Role of Endogenous Kallistatin in Vascular Injury and Senescence by Inhibiting Oxidative Stress and Inflammation

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Julie Chao ◽  
Youming Guo ◽  
Lee Chao
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Nadph Oxidase ◽  
Vascular Injury ◽  
Oxidase Activity ◽  
Sirtuin 1 ◽  
Mouse Lung ◽  
Heparin Binding ◽  
Diabetic Mice ◽  
Nadph Oxidase Activity

Kallistatin was identified in human plasma as a tissue kallikrein-binding protein and a serine proteinase inhibitor. Kallistatin exerts pleiotropic effects on angiogenesis, oxidative stress, inflammation, apoptosis, fibrosis, and tumor growth. Kallistatin levels are markedly reduced in patients with coronary artery disease, sepsis, diabetic retinopathy, inflammatory bowel disease, pneumonia, and cancer. Moreover, plasma kallistatin levels are positively associated with leukocyte telomere length in young African Americans, indicating the involvement of kallistatin in aging. In addition, kallistatin treatment promotes vascular repair by increasing the migration and function of endothelial progenitor cells (EPCs). Kallistatin via its heparin-binding site antagonizes TNF-α-induced senescence and superoxide formation, while kallistatin’s active site is essential for inhibiting miR-34a synthesis, thus elevating sirtuin 1 (SIRT1)/eNOS synthesis in EPCs. Kallistatin inhibits oxidative stress-induced cellular senescence by upregulating Let-7g synthesis, leading to modulate Let-7g-mediated miR-34a-SIRT1-eNOS signaling pathway in human endothelial cells. Exogenous kallistatin administration attenuates vascular injury and senescence in association with increased SIRT1 and eNOS levels and reduced miR-34a synthesis and NADPH oxidase activity, as well as TNF-α and ICAM-1 expression in the aortas of streptozotocin- (STZ-) induced diabetic mice. Conversely, endothelial-specific depletion of kallistatin aggravates vascular senescence, oxidative stress, and inflammation, with further reduction of Let-7g, SIRT1, and eNOS and elevation of miR-34a in mouse lung endothelial cells. Furthermore, systemic depletion of kallistatin exacerbates aortic injury, senescence, NADPH oxidase activity, and inflammatory gene expression in STZ-induced diabetic mice. These findings indicate that endogenous kallistatin displays a novel role in protection against vascular injury and senescence by inhibiting oxidative stress and inflammation.

Thioredoxin-1/peroxiredoxin-1 as sensors of oxidative stress mediated by NADPH oxidase activity in atherosclerosis

2015 ◽  
Vol 86 ◽  
pp. 352-361 ◽  
Author(s):  
Julio Madrigal-Matute ◽  
Carlos-Ernesto Fernandez-Garcia ◽  
Luis Miguel Blanco-Colio ◽  
Elena Burillo ◽  
Ana Fortuño ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Nadph Oxidase Activity ◽  
Peroxiredoxin 1 ◽  
Thioredoxin 1

scholarly journals Effect of renin inhibition and AT1R blockade on myocardial remodeling in the transgenic Ren2 rat

2008 ◽  
Vol 295 (1) ◽  
pp. E103-E109 ◽  
Author(s):  
Adam Whaley-Connell ◽  
Javad Habibi ◽  
Shawna A. Cooper ◽  
Vincent G. DeMarco ◽  
Melvin R. Hayden ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Myocardial Remodeling ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Nadph Oxidase Activity ◽  
Renin Inhibition

Angiotensin II (Ang II) stimulation of the Ang type 1 receptor (AT1R) facilitates myocardial remodeling through NADPH oxidase-mediated generation of oxidative stress. Components of the renin-angiotensin system constitute an autocrine/paracrine unit in the myocardium, including renin, which is the rate-limiting step in the generation of Ang II. This investigation sought to determine whether cardiac oxidative stress and cellular remodeling could be attenuated by in vivo renin inhibition and/or AT1R blockade in a rodent model of chronically elevated tissue Ang II levels, the transgenic (mRen2)27 rat (Ren2). The Ren2 overexpresses the mouse renin transgene with resultant hypertension, insulin resistance, and cardiovascular damage. Young (6- to 7-wk-old) heterozygous (+/−) male Ren2 and age-matched Sprague-Dawley rats were treated with the renin inhibitor aliskiren, which has high preferential affinity for human and mouse renin, an AT1R blocker, irbesartan, or placebo for 3 wk. Myocardial NADPH oxidase activity and immunostaining for NADPH oxidase subunits and 3-nitrotyrosine were evaluated and remodeling changes assessed by light and transmission electron microscopy. Blood pressure, myocardial NADPH oxidase activity and subunit immunostaining, 3-nitrotyrosine, perivascular fibrosis, mitochondrial content, and markers of activity were significantly increased in Ren2 compared with SD littermates. Both renin inhibition and blockade of the AT1R significantly attenuated cardiac functional and structural alterations, although irbesartan treatment resulted in greater reductions of both blood pressure and markers of oxidative stress. Collectively, these data suggest that both reduce changes driven, in part, by Ang II-mediated increases in NADPH oxidase and, in part, increases in blood pressure.

scholarly journals Erythrocyte NADPH oxidase activity modulated by Rac GTPases, PKC, and plasma cytokines contributes to oxidative stress in sickle cell disease

Blood ◽  
2013 ◽  
Vol 121 (11) ◽  
pp. 2099-2107 ◽  
Author(s):  
Alex George ◽  
Suvarnamala Pushkaran ◽  
Diamantis G. Konstantinidis ◽  
Sebastian Koochaki ◽  
Punam Malik ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sickle Cell Disease ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Ros Production ◽  
Cell Disease ◽  
Nadph Oxidase Activity ◽  
Rac Gtpases ◽  
Key Points ◽  
Plasma Cytokines

Key Points Sickle RBC ROS production is mediated in part by NADPH oxidase activity. Sickle RBC ROS production can be induced by plasma signaling molecules.

scholarly journals The Post-Ischemic Increase in GluA2 Ser880 Phosphorylation Involves NADPH Oxidase

2018 ◽  
Vol 4 (1) ◽  
pp. 170-181
Author(s):  
Darrell A. Jackson ◽  
Fanny Astruc-Diaz ◽  
Nicole M. Byrnes ◽  
Phillip H. Beske
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Hippocampal Slices ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Glucose Deprivation ◽  
Subunit Composition ◽  
Stress Signaling ◽  
Scaffolding Proteins ◽  
Nadph Oxidase Activity

Most 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid receptors (AMPARs) expressed on adult hippocampal pyramidal neurons contain the edited form of GluA2 (Q607R) and are thus impermeable to Ca2+/Zn2+ entry.  Following ischemic injury, these receptors undergo a subunit composition change, switching from a GluA2-containing Ca2+/Zn2+-impermeable AMPAR to a GluA2-lacking Ca2+/Zn2+-permeable AMPAR. Recent studies indicate that an oxidative stress signaling pathway is responsible for the I/R-induced changes in AMPAR subunit composition.  Studies suggest that nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase), a superoxide generator, is the source that initiates the oxidative stress-signaling cascade during post-ischemic reperfusion. The objective of the present study was to determine if suppression of NADPH oxidase activity prevents the increase in phosphorylation and subsequent internalization of the GluA2 AMPAR subunit during reperfusion of post-ischemic hippocampal slices. In this study, we demonstrated that exposure of adult rat hippocampal slices to oxygen glucose deprivation/reperfusion (OGD/R) results in an increase in Ser880 phosphorylation of the GluA2 subunit.  The increase in Ser880 phosphorylation resulted in the dissociation of GluA2 from the scaffolding proteins Glutamate receptor-interacting protein 1 (GRIP1) and AMPAR binding protein (ABP), thus enabling the association of GluA2 with protein interacting with C kinase 1 (PICK1). OGD/R also resulted in an increase in the association of activated protein kinase C ? (PKC?) with PICK1. We have found that pharmacological inhibition of NADPH oxidase with apocynin diminishes the OGD/R-induced increase in activated PKC? association with PICK1 and subsequent Ser880 phosphorylation of GluA2. Suppression of NADPH oxidase activity also blunted OGD/R-induced decreased association of GluA2 with the scaffolding proteins GRIP1 and ABP.  Protein phosphatase 2A (PP2A), which regulates PKC? activity by dephosphorylating the kinase, was inactivated by OGD/R-induced increase in tyrosine phosphorylation of the phosphatase (Y307). Inhibition of NADPH oxidase activity ameliorated OGD/R-induced PP2A phosphorylation and inactivation. Our findings are consistent with a model of OGD/R-induced Ser880 phosphorylation of GluA2 that implicates NADPH oxidase mediated inactivation of PP2A and sustained PKC? phosphorylation of GluA2.

Abstract 142: Angiotensin II Type 1 Receptor Autoantibody Inhibition Improves Blood Pressure and Markers of Neurological Damage and Oxidative Stress in Brains of Placental Ischemic Rats During Pregnancy

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Mark W Cunningham ◽  
Venkata Ramana Vaka ◽  
Lorena Amaral ◽  
Fan Fan ◽  
Tarek Ibrahim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Neurological Complications ◽  
Peptide Sequence ◽  
Inhibitory Peptide ◽  
Nadph Oxidase Activity

Preeclampsia (PE), hypertension in response to placental ischemia, is associated with angiotensin II type 1 receptor agonistic autoantibodies (AT1-AA), oxidative stress, and neurological complications, such as headaches, blurred vision, and seizures which could lead to stroke and death. We hypothesize that AT1AAs play a role in the cerebral pathology of PE. The objective of this study was to determine if administration of a specific peptide sequence to inhibit the AT1-AA from binding to the AT1 receptor, will improve blood pressure (MAP) and cerebral oxidative stress in the reduced uterine perfusion pressure (RUPP) rat model of PE. Pregnant Sprague Dawley rats were divided into 2 groups: RUPP (n=5) and RUPP+AT1-AA inhibitory peptide (7AA) (n=3). RUPP surgery was performed on gestational day (GD) 14 and the 7AA was administered (2ug/μl saline) via mini-osmotic pumps. On GD 19, MAP was determined and brains collected. Western blots were stained for Glial Fibrillary Acidic Protein (GFAP), endothelial NO synthase (eNOS), phosphorylated eNOS and NADPH oxidase activity was determined using chemilumenescence. MAP was decreased in RUPP+7AA vs. RUPP (95±2 vs. 130±6 mmHg). Brain/body weight ratio, which is indicative of edema, was reduced in RUPP+7AA (5.8±0.25 vs. 6.5±0.25 grams) vs. RUPP. NADPH oxidase activity was lower in RUPP+7AA (33275±3122 vs. 57408±10508 RLU/min/mg protein). Phosphorylated eNOS was 2 fold higher in the RUPP+7AA vs. RUPP (0.4±0.1 vs. 0.2±0.04 AU) and the phosphorylated eNOS/eNOS ratio was elevated (0.4±0.12 vs. 0.2±0.04 AU). GFAP a marker for activated astrocytes that increases during neurologic injury and serves as a compensatory mechanism for brain injury recovery was elevated in RUPP+7AA vs. RUPP (3.2±1.3 vs. 0.5±0.2 AU). Administration of AT1-AA inhibitory peptide to RUPP rats decreased blood pressure and improved markers of NO bioavailability, injury (GFAP), and cerebral swelling. In conclusion, our preliminary data suggests that AT1-AA inhibition could be a potential therapy to improve peripheral and neurological complications during PE. Research Supported by T32HL105324 (Cunningham), RO1HD067541-06 (LaMarca), DK-104184 (Roman), 050049 (Fan), P20-GM-104357 (cores B and C-Roman; Pilot-Fan) and AHA 16GRNT31200036 (Fan).

Abstract 077: Renal Denervation Attenuates Salt-Sensitive Hypertension and Oxidative Stress in Rats with Unilateral Hydronephrosis

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Maria Peleli ◽  
Ammar Al-Mashhadi ◽  
Ting Yang ◽  
Erik G Persson ◽  
Mattias Carlstrom
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Nadph Oxidase ◽  
Mrna Expression ◽  
Oxidase Activity ◽  
Renal Denervation ◽  
Urine Osmolality ◽  
Nadph Oxidase Activity ◽  
Urine Production ◽  
Salt Sensitive Hypertension

Hydronephrotic rats and mice have impaired renal function and develop salt-sensitive hypertension, which are associated with oxidative stress. Increased sympathetic nerve activity and oxidative stress in the kidney may play important roles in renovascular hypertension. This study aimed to investigate the contribution of renal sympathetic nerve activity in the development of hypertension in hydronephrosis. A partial unilateral ureteral obstruction (PUUO) was created in 3-weeks old rats to induce hydronephrosis. Surgical denervation, or sham operation, of the PUUO kidney was performed at the time of ureteral obstruction and again 4-weeks later during implantation of a telemetric blood pressure device. Hydronephrotic animals had higher blood pressure (115±3 mmHg) compared with controls (87±1 mmHg), and the blood pressure elevation to a high salt diet was more pronounced (15±2 vs 5±1 mmHg) (p<0.05). Hydronephrosis was also associated with increased urine production (40±4 μl/24h/gBW) and lower urine osmolality (1242±109 mOsm/kg H2O) compared with controls (28±3 μl/24h/gBW and 1751±83 mOsm) (p<0.05). Renal denervation in rats with PUUO attenuated hypertension (97±3 mmHg) and normalized salt-sensitivity (5±1 mmHg), urine production (32±2 μl/24h/gBW) and urine osmolality (1586±127 mOsm/kg H2O) (p<0.05). NADPH oxidase activity in renal cortex from PUUO rats was increased compared with controls (4608±396 vs 3373±217 CLU/min/mg protein) (p<0.05). This was associated with increased cortical mRNA expression of Nox2 (2.3±0.43), p22phox (2.65±0.67) and p47phox (1.39±0.23) compared with controls (p<0.05). Remarkably, denervation in PUUO rats normalized both NADPH oxidase activity (3363±258 CLU/min/mg protein) and mRNA expression of Nox2, p22phox and p47phox (p<0.05). Interestingly, also myocardial tissue from PUUO displayed increased mRNA expression of Nox2 (1.68±0.23) and p22phox (2.82±0.51) compared with control rats, and this was normalized by renal denervation (0.81±0.43) (p<0.05). In conclusion, renal denervation of the hydronephrotic kidney attenuates hypertension and salt-sensitivity, and restores renal excretion pattern. Mechanistically, this is associated with reduced renal NADPH oxidase activity and expression.

Abstract 211: Inhibition of Heme Oxygenase-1 (HO-1) Induces Mild Hypertension in Pregnant Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Eric M George ◽  
Frank Spradley ◽  
Joey P Granger
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Late Gestation ◽  
Heme Oxygenase 1 ◽  
Maternal Circulation ◽  
Pregnant Rats ◽  
Nadph Oxidase Activity ◽  
Significant Difference

In the preeclamptic patient, inadequate remodeling of the maternal vasculature exacerbates this effect, causing dramatically increased oxidative stress in the placenta, which has been shown to be an important component of the maternal hypertension. There is also increasing awareness that HO-1 may act as an important regulator of placental function during normal pregnancy and decreases in HO-1 activity have been implicated in the pathogenesis of preeclampsia. While previous work in pregnant mice demonstrated that pharmacological inhibition of HO-1 leads to elevations in blood pressure, the mechanisms involved in the hypertension are unclear. The purpose of this study was to test the hypothesis that HO inhibition in late gestation leads to increases in maternal blood pressure by altering angiogenic balance and increasing placental oxidative stress in pregnant rats. HO activity was inhibited with tin mesoporphyrin (SnMP) was administered on gestational day 14, and blood pressure was measured on gestational day 19 by indwelling carotid catheter before sacrifice. In response to SnMP treatment, maternal MAP was significantly increased (99±1 vs 113±2 mmHg, p<0.05, n=15 per group). Placental sFlt-1 (631±47 vs 648±26 pg/mg, p=0.76) levels in the placenta were not affected by HO inhibition. Additionally, there was no significant difference in free VEGF in the maternal circulation (287±22 vs 329±14 pg/ml, p=0.11). There was, however, a significant increase in placental NADPH oxidase activity in SnMP treated rats (2021±238 vs 3005±301 RLU/min/mg, p<0.05) as determined by NADPH dependent lucigenin luminescence. This is likely due to decreased production of bilirubin, which is known to inhibit NADPH oxidase activity, and suggests an important role for HO-1 as an antioxidant in the developing placenta.

Effects of Gentiopicroside on Oxidative Stress and Apoptosis in Gastric Cancer Cells

2021 ◽  
Vol 11 (3) ◽  
pp. 553-559
Author(s):  
Xinyi Wu ◽  
Suying Li ◽  
Shuo An
Keyword(s):  
Oxidative Stress ◽  
Gastric Cancer ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Related Factor ◽  
Sod Activity ◽  
Nadph Oxidase Activity ◽  
Expression Levels ◽  
Apoptosis Rate ◽  
Mda Content

Gastric cancer (GC) cells were sorted into six groups: NC, different concentrations of gentiopi-croside, pcDNA-NC, pcDNA-Nrf2, pcDNA-NC + gentiopicroside, and pcDNA-Nrf2 + gentiopicroside. The detection and comparison of cell survival and apoptosis showed that the activity of GC cells decreased and the apoptosis rate increased after gentiopicroside treatment. Western blot detection was performed to determine the expression levels of proliferating cell nuclear antigen (PCNA), B-cell leukemia/lymphoma-2 (Bcl-2)-associated X protein (Bax), Bcl-2, Kelch-like epichlorohydrin-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and antioxidant response element (ARE). Kits were used to determine the malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. The MDA content, NADPH oxidase activity, and Keap1 and Bax expression levels increased, and the SOD activity and Bcl-2, PCNA, Nrf2, and ARE expression levels decreased. Nrf2 overexpression increased the cell activity, SOD activity, and Nrf2, ARE, PCNA, and Bcl-2 expression levels and reduced the apoptosis rate, MDA content, NADPH oxidase activity, and Bax and Keap1 expression levels. At the same time, Nrf2 overexpression reversed the effects of gentiopicroside on oxidative stress and apoptosis of GC cells. These results suggest that gentiopicroside probably promotes oxidative stress and apoptosis of GC cells by inhibiting the Keap1/Nrf2/ARE signaling pathway.

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