Nandrolone attenuates aortic adaptation to exercise in rats

Sun, Ming; Shen, Weili; Zhong, Mingkang; Wu, Pingping; Chen, Hong; Lu, Aiyun

doi:10.1093/cvr/cvs423

Cited by 24 publications

(13 citation statements)

References 44 publications

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“…Fusion/fission balance plays an important role in determining the fate of depolarized mitochondria (16, 17) and if altered, can produce dysfunctional or damaged mitochondria that are subsequently degraded by autophagy. Our data shows that NLRP3 −/− lungs had exaggerated induction of mitochondrial fusion proteins MFN1, MFN2 and OPA1 during hyperoxia compared to WT lungs, which was blunted in the absence of PINK1 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Endothelial PINK1 Mediates the Protective Effects of NLRP3 Deficiency during Lethal Oxidant Injury

Zhang

Sauler

Shinn

et al. 2014

The Journal of Immunology

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High levels of inspired oxygen, hyperoxia, are frequently used in patients with acute respiratory failure. Hyperoxia can exacerbate acute respiratory failure, which has high mortality and no specific therapies. We identified a novel roles for PINK1 (PTEN-induced putative kinase 1), a mitochondrial protein, and the cytosolic innate immune protein, NLRP3, in the lung and endothelium. We generated double knockouts (PINK1−/−/NLRP3−/−) as well as cell-targeted PINK1 silencing and lung-targeted overexpression constructs to specifically show that PINK1 mediates cytoprotection in wild type (WT) and NLRP3−/− mice. The ability to resist hyperoxia is proportional to PINK1 expression – PINK1−/− mice were the most susceptible, WT mice, which induced PINK1 after hyperoxia, had intermediate susceptibility and NLRP3−/− mice, which had high basal and hyperoxia-induced PINK1, were the least susceptible. Genetic deletion of PINK1 or PINK1 silencing in the lung endothelium increased susceptibility to hyperoxia via alterations in autophagy/mitophagy, proteasome activation, apoptosis and oxidant generation.

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Section: Resultsmentioning

confidence: 99%

Endothelial PINK1 Mediates the Protective Effects of NLRP3 Deficiency during Lethal Oxidant Injury

Zhang

Sauler

Shinn

et al. 2014

The Journal of Immunology

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“…Likewise, Chaves et al [15,16] showed that in spite of the beneficial effect of HIE on the heart through increased activity of antioxidant enzymes, Nandrolone administration induced lower SOD, GPx and glutathione reductase (GR) activity when compared to control and trained animals. Similarly, Sun et al [59] demonstrated that the combination of Nandrolone and an aerobic physical training increased MDA and PCC, and decreased SOD and NQO-1 protein levels on aortic large vessels. On the other hand, Saborido et al [54] observed that Stanozolol administration might protect rat gastrocnemius mitochondria against oxidative damage of proteins and changes in membrane fatty acid composition induced by acute exercise.…”

Section: High-intensity Exercise Anabolic Androgenic Steroids and Brmentioning

confidence: 87%

High-intensity Exercise Modifies the Effects of Stanozolol on Brain Oxidative Stress in Rats

et al. 2015

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We analyzed the effects of high-intensity exercise (HIE) and anabolic androgenic steroids (AAS) on brain redox status. 40 male Wistar rats were randomly distributed in 4 experimental groups (n=10) with or without HIE and with or without weekly Stanozolol administration. Thiobarbituric acid-reactive substances (TBARs) and protein carbonyl content (PCC) were assessed. Total superoxide dismutase (tSOD), manganese superoxide dismutase (Mn-SOD), copper/zinc superoxide dismutase (CuZn-SOD) and catalase (CAT) activities were measured. Finally, protein expression levels of glutathione peroxidase (GPx), NAD(P)H dehydrogenase, Quinone 1 (NQO1), NF-E2-Related Factor 2 (Nrf2), glial fibrillary acidic protein (GFAP), nuclear factor kappa β p65 (NF-κβ) and signal transducer and activator of transcription 3 were determined. Brain PCC concentrations were lower in the HIE groups compared to the untrained controls, whereas CAT activity was higher (both, p<0.01). Both HIE and AAS groups exhibited higher expression levels of GFAP and GPx, but lower NQO1 levels (all, p<0.05). There were increased expression levels of NF-κβ in the AAS groups (p<0.01). In addition, there was increased expression of Nrf2 in the HIE groups (p<0.001). HIE*AAS interactions were found on TBARs content and GFAP expression, with HIE downregulating and upregulating AAS-mediated increases in TBARs and GFAP, respectively (p<0.05). Overall, HIE appeared to reduce the AAS-mediated negative effect on brain redox status.

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“…Adenoviral‐medi‐ated expression of HO‐1 inhibited DISC formation and caspase 3/9 activation, diminished the expression of Beclin‐1, and partially inhibited the processing of LC3B‐I to LC3B‐II in cigarette smoke‐exposed epithelial cells, Aerobic training increased HO‐1 levels, induced mitochondrial complexes I and V, increased mitochondrial DNA copy number, and also increased conversion of LC3‐I to LC3‐II ( i.e. , increased autophagy), which resulted in improved ace‐tylcholine‐induced vascular relaxation (47). HO‐1 promotes autophagy and elimination of damaged mitochondria in order to repress oxidative stress in LPS‐treated rat liver (48).…”

Section: Discussionmentioning

confidence: 99%

“…Mitochondrial fission and fusion involve 4 dynamin‐related GTPase family proteins, including MFN1, MFN2, OPA1, and DRP1. Fusion/fission balance plays an important role in determining the fate of depolarized mitochondria (24, 57). Fusion/fission imbalance can lead to dysfunctional or damaged mitochondria and subsequent degradation by autophagy.…”

Section: Discussionmentioning

confidence: 99%

Lung endothelial HO‐1 targetingin vivousing lentiviral miRNA regulates apoptosis and autophagy during oxidant injury

et al. 2013

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The lung endothelium is a major target for inflammatory and oxidative stress. Heme oxygenase-1 (HO-1) induction is a crucial defense mechanism during oxidant challenges, such as hyperoxia. The role of lung endothelial HO-1 during hyperoxia in vivo is not well defined. We engineered lentiviral vectors with microRNA (miRNA) sequences controlled by vascular endothelium cadherin (VE-cad) to study the specific role of lung endothelial HO-1. Wild-type (WT) murine lung endothelial cells (MLECs) or WT mice were treated with lentivirus and exposed to hyperoxia (95% oxygen). We detected HO-1 knockdown (∼55%) specifically in the lung endothelium. MLECs and lungs showed approximately a 2-fold increase in apoptosis and ROS generation after HO-1 silencing. We also demonstrate for the first time that silencing endothelial HO-1 has the same effect on lung injury and survival as silencing HO-1 in multiple lung cell types and that HO-1 regulates caspase 3 activation and autophagy in endothelium during hyperoxia. These studies demonstrate the utility of endothelial-targeted gene silencing in vivo using lentiviral miRNA constructs to assess gene function and that endothelial HO-1 is an important determinant of survival during hyperoxia.

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Nandrolone attenuates aortic adaptation to exercise in rats

Abstract: These results demonstrate that nandrolone attenuates aortic adaptations to exercise by regulating mitochondrial dynamic remodelling, including down-regulation of mitochondrial biogenesis and intensive autophagy.

Cited by 24 publications

References 44 publications

Endothelial PINK1 Mediates the Protective Effects of NLRP3 Deficiency during Lethal Oxidant Injury

Endothelial PINK1 Mediates the Protective Effects of NLRP3 Deficiency during Lethal Oxidant Injury

High-intensity Exercise Modifies the Effects of Stanozolol on Brain Oxidative Stress in Rats

Lung endothelial HO‐1 targetingin vivousing lentiviral miRNA regulates apoptosis and autophagy during oxidant injury

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