Myocardial protection with endogenous overexpression of manganese superoxide dismutase

Suzuki, Ken; Sawa, Yoshiki; Ichikawa, Hajime; Kaneda, Yasufumi; Matsuda, Hikaru

doi:10.1016/s0003-4975(99)00726-2

Cited by 23 publications

(8 citation statements)

References 17 publications

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“…Thus it is logical to try and develop strategies to intervene with excessive generation of mitochondrial oxidants. Overexpression (endogenous or exogenous) or induction of MnSOD has been shown to offer protection from I/R-induced cellular damage in the heart, brain, liver, and kidney (11,29,47,48,61). We and others have shown that ROS scavengers significantly protect against the renal I/R injury (8,52,63).…”

mentioning

confidence: 89%

“…Complete loss of this enzyme results in massive oxidative stress leading to neonatal death as evidenced from complete MnSOD KO mice (33,36). Numerous studies have reported the loss of MnSOD enzyme activity following I/R within the heart (2,11,26,39,61), liver (23,48), and kidney (17). In fact, our laboratory showed that using the rodent I/R model, Mn-SOD was inactivated prior to the onset of renal damage, which suggests that oxidant generation/mitochondrial damage are upstream to renal damage (15).…”

mentioning

confidence: 99%

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Role of reduced manganese superoxide dismutase in ischemia-reperfusion injury: a possible trigger for autophagy and mitochondrial biogenesis?

Parajuli

MacMillan-Crow

2013

American Journal of Physiology-Renal Physiology

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Excessive generation of superoxide and mitochondrial dysfunction has been described as being important events during ischemia-reperfusion (I/R) injury. Our laboratory has demonstrated that manganese superoxide dismutase (MnSOD), a major mitochondrial antioxidant that eliminates superoxide, is inactivated during renal transplantation and renal I/R and precedes development of renal failure. We hypothesized that MnSOD knockdown in the kidney augments renal damage during renal I/R. Using newly characterized kidney-specific MnSOD knockout (KO) mice the extent of renal damage and oxidant production after I/R was evaluated. These KO mice (without I/R) exhibited low expression and activity of MnSOD in the distal nephrons, had altered renal morphology, increased oxidant production, but surprisingly showed no alteration in renal function. After I/R the MnSOD KO mice showed similar levels of injury to the distal nephrons when compared with wild-type mice. Moreover, renal function, MnSOD activity, and tubular cell death were not significantly altered between the two genotypes after I/R. Interestingly, MnSOD KO alone increased autophagosome formation, mitochondrial biogenesis, and DNA replication/repair within the distal nephrons. These findings suggest that the chronic oxidative stress as a result of MnSOD knockdown induced multiple coordinated cell survival signals including autophagy and mitochondrial biogenesis, which protected the kidney against the acute oxidative stress following I/R.

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confidence: 89%

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confidence: 99%

Role of reduced manganese superoxide dismutase in ischemia-reperfusion injury: a possible trigger for autophagy and mitochondrial biogenesis?

Parajuli

MacMillan-Crow

2013

American Journal of Physiology-Renal Physiology

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“…There are a growing number of experimental studies that associate certain types of intervention or stimulus, such as long-term manipulation of diet, genetic overexpression of enzymes and antioxidant compounds, and supplementation and/or deficiency of antioxidants, with a greater or lesser susceptibility to cardiac damage when it is exposed to oxidative stress-based conditions [40,[54][55][56][57][58]. Thus, since cardiac muscle tissue appears capable of a series of adaptations when submitted to certain chronic stimuli, the role of regular endurance training in increasing cardiac tolerance to oxidative stress and damage is still a subject worthy of investigation.…”

Section: Chronic Exercise and Antioxidant Systemsmentioning

confidence: 99%

Exercise-induced cardioprotection — biochemical, morphological and functional evidence in whole tissue and isolated mitochondria

Ascensão

Ferreira

Magalhães

2007

International Journal of Cardiology

132

104

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“…The study showed that gene therapy by HSP70 has a potential to enhance myocardial tolerance to ischemia better than the heat stress by itself [3]. In a similar model of HSP70 gene therapy by intracoronary infusion of the HVJ-liposome containing human HSP70 gene, Suzuki and colleagues [51] showed that the enhanced activity of mitochondrial manganese SOD (Mn-SOD) during ischemia-reperfusion injury, is one of the possible mechanisms explaining HSP70-induced myocardial protection, likely by mitochondrial protection and apoptosis reduction [52]. After ischemia, Mn-SOD content and activity in the HSP70-transfected hearts enhanced compared to the controls, and this was further associated with improved mitochondrial respiratory function [51].…”

Section: Gene Therapy Targeting Oxidative Stressmentioning

confidence: 99%

Cardioprotection by gene therapy

Madonna

Dessalvi

Deidda

et al. 2015

International Journal of Cardiology

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Ischemic heart disease remains the leading cause of death worldwide. Ischemic pre-, post-, and remote conditionings trigger endogenous cardioprotection that renders the heart resistant to ischemic-reperfusion injury (IRI). Mimicking endogenous cardioprotection by modulating genes involved in cardioprotective signal transduction provides an opportunity to reproduce endogenous cardioprotection with better possibilities of translation into the clinical setting. Genes and signaling pathways by which conditioning maneuvers exert their effects on the heart are partially understood. This is due to the targeted approach that allowed identifying one or a few genes associated with IRI and cardioprotection. Genes critical for signaling pathways in cardioprotection include protectomiRs (e.g., microRNA 125b*), ZAC1 transcription factor, pro-inflammatory genes such as cycloxygenase (COX)-2 and inducible nitric oxide synthase (iNOS), antioxidant enzymes such as hemoxygenase (HO)-1, extracellular and manganese superoxidase dismutases (ec-SOD and Mg-SOD), heat shock proteins (HSPs), growth factors such as insulin like growth factor (IGF)-1 and hepatocyte growth factor (HGF), antiapoptotic proteins such as Bcl-2 and Bcl-xL, pro-apoptotic proteins such as FasL, Bcl-2, Bax, caspase-3 and p53, and proangiogenic genes such as TGFbeta, sphingosine kinase 1 (SPK1), and PI3K-Akt. By identifying the gene expression profiles of IRI and ischemic conditioning, one may reveal potential gene targets responsible for cardioprotection. In this manuscript, we review the current state of the art of gene therapy in cardioprotection and propose that gene expression analysis facilitates the identification of individual genes associated with cardioprotection. We discuss signaling pathways associated with cardioprotection that can be targeted by gene therapy to achieve cardioprotection.

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Myocardial protection with endogenous overexpression of manganese superoxide dismutase

Cited by 23 publications

References 17 publications

Role of reduced manganese superoxide dismutase in ischemia-reperfusion injury: a possible trigger for autophagy and mitochondrial biogenesis?

Role of reduced manganese superoxide dismutase in ischemia-reperfusion injury: a possible trigger for autophagy and mitochondrial biogenesis?

Exercise-induced cardioprotection — biochemical, morphological and functional evidence in whole tissue and isolated mitochondria

Cardioprotection by gene therapy

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