Mitochondrial Coenzyme Q Protects Sepsis-Induced Acute Lung Injury by Activating PI3K/Akt/GSK-3<i>β</i>/mTOR Pathway in Rats

Li, Ruirui; Ren, Tao; Zeng, Jianqiong

doi:10.1155/2019/5240898

Cited by 56 publications

(43 citation statements)

References 34 publications

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“…Thus, mitoQ exerts protective effect on I/R-induced intestinal barrier dysfunction [ 40 ]. Recently Ruirui Li and his colleague revealed that mitoQ protected lung function and inhibited cell apoptosis in lung tissue by activating the PI3K/Akt/GSK-3 beta/mTOR pathway [ 41 ]. Our findings indicate that mitoQ plays an efficient role in LPS induced acute lung injury via inhibiting mitochondrial ROS (mtROS) production in both in vivo and in vitro .…”

Section: Discussionmentioning

confidence: 99%

MitoQ protects against hyperpermeability of endothelium barrier in acute lung injury via a Nrf2-dependent mechanism

et al. 2021

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Recently, numerous evidence has revealed that excessive reactive oxygen species (ROS) production and mitochondrial disruption during acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS) will aggravate the inflammatory process. To identify whether antioxidation can be one of the treatment strategies during this progress, we chose mitoQ, a mitochondria-targeted antioxidant that was proved to be effective in reducing ROS generated in mitochondria, as a ROS scavenger to investigate the role of antioxidation in ALI. We demonstrated that overoxidation occurred during the process of ALI, which could be reduced by mitoQ. In the meantime, apoptosis of endothelial cells of ALI mice, accompanied by hyperpermeability of pulmonary vascular and impaired pulmonary function, was partially reversed following an intraperitoneal injection of mitoQ. Moreover, in in vitro study, lipopolysaccharides (LPS) induced excessive ROS production, mitochondrial dysfunction and apoptosis in human pulmonary microvascular endothelial cells (HPMECs), which were rectified by mitoQ. To explore underlying mechanisms, we proceeded RNA-sequencing and found significantly upregulated expression of musculoaponeurotic fibrosarcoma F ( MafF) in mitoQ treated group. Additionally, mitoQ inhibited the degradation and increased nuclear translocation of NF-E2-related factor 2 (Nrf2) and upregulated its downstream antioxidant response elements (AREs), such as heme oxygenase (HO)-1 and NAD(P)H:quinone oxidoreductase (NQO)-1. This effect was abolished by transfecting HPMECs with Nrf2 or Maff siRNA. In Nrf2 deficient mice, the protective effects of mitoQ on LPS model of ALI were largely vanished. Taken together, these results provide insights into how antioxidation exerts beneficial effects on ALI via maintaining mitochondrial hemostasis, inhibiting endothelial cells apoptosis, attenuating the endothelial disruption and regulating lung inflammation via Nrf2-MafF/ARE pathway.

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Section: Discussionmentioning

confidence: 99%

MitoQ protects against hyperpermeability of endothelium barrier in acute lung injury via a Nrf2-dependent mechanism

et al. 2021

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“…The rat sepsis model was established using the cecal ligation and puncture (CLP) method, as previously described ( 17 ). Briefly, all rats were deprived of from food 12 h before surgery, but had free access to water during this time.…”

Section: Methodsmentioning

confidence: 99%

Sufentanil attenuates inflammation and oxidative stress in sepsis-induced acute lung injury by downregulating KNG1 expression

Wang

Han

et al. 2020

Mol Med Rep

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The present study aimed to investigate the effects of sufentanil on sepsis-induced acute lung injury (ali), and identify the potential molecular mechanisms underlying its effect. in order to achieve this, a rat sepsis model was established. Following treatment with sufentanil, the lung wet/dry (W/d) weight ratio was calculated. Histopathological analysis was performed via hematoxylin and eosin staining. Levels of inflammatory factors in bronchoalveolar lavage fluid were determined via eliSa. Furthermore, malondialdehyde (Mda) content and the activities of superoxide dismutase (Sod), catalase (caT) and glutathione peroxidase (GSH-Px) in tissue homogenates were assessed using commercial kits. Western blot analysis was performed to determine kininogen-1 (KnG1) protein expression. in addition, alveolar epithelial type ii cells (aec ii) were stimulated with lipopolysaccharide (LPS) to mimic ALI. The levels of inflammation and oxidative stress were evaluated following overexpression of KnG1. Protein expression levels of nuclear factor-κB (nF-κB) and nuclear factor erythroid 2-related factor 2 (nrf2)/heme oxygenase-1 (Ho-1) signaling were determined via western blot analysis. The results of the present study demonstrated that sufentanil alleviated histopathological injury and the W/d ratio in lung tissue. Following treatment with sufentanil, levels of inflammatory factors also decreased, accompanied by decreased concentrations of Mda, and increased activities of Sod, caT and GSH-Px. notably, KnG1 was decreased in lung tissues following treatment with sufentanil. Furthermore, overexpression of KnG1 attenuated the inhibitory effects of sufentanil on lPS-induced inflammation and oxidative stress in aec ii. Sufentanil markedly downregulated nF-κB expression, while upregulating nrf2 and Ho-1 expression levels, which was reversed following overexpression of KnG1. Taken together, the results of the present study suggested that sufentanil may alleviate inflammation and oxidative stress in sepsis-induced ali by downregulating KnG1 expression.

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“…But (Rademann et al 2017) (Lowes et al 2008) (Supinski et al 2009) (Zang et al 2012) (Lowes et al 2013) (Wu et al 2015) ) (Prauchner 2017) (Fock et al 2018) (Li, Ren, et al 2019) But (Rademann et al 2017) (Elsakka et al 2007) (Paludo et al 2013) (Majolo et al 2015) (continued) (Zhao et al 2004) (Adlam et al 2005) (Cho J et al 2007) (Neuzil et al 2007) (Bakeeva et al 2008) (Skulachev et al 2009 (Keller et al 1998) (Murakami et al 1998) (Fujimura et al 1999) (Kim et al 2002)…”

Section: Pathologymentioning

confidence: 99%

Riding the tiger – physiological and pathological effects of superoxide and hydrogen peroxide generated in the mitochondrial matrix

Brand

2020

Critical Reviews in Biochemistry and Molecular Biology

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Elevated mitochondrial matrix superoxide and/or hydrogen peroxide concentrations drive a wide range of physiological responses and pathologies. Concentrations of superoxide and hydrogen peroxide in the mitochondrial matrix are set mainly by rates of production, the activities of superoxide dismutase-2 (SOD2) and peroxiredoxin-3 (PRDX3), and by diffusion of hydrogen peroxide to the cytosol. These considerations can be used to generate criteria for assessing whether changes in matrix superoxide or hydrogen peroxide are both necessary and sufficient to drive redox signaling and pathology: is a phenotype affected by suppressing superoxide and hydrogen peroxide production; by manipulating the levels of SOD2, PRDX3 or mitochondria-targeted catalase; and by adding mitochondria-targeted SOD/catalase mimetics or mitochondria-targeted antioxidants? Is the pathology associated with variants in SOD2 and PRDX3 genes? Filtering the large literature on mitochondrial redox signaling using these criteria highlights considerable evidence that mitochondrial superoxide and hydrogen peroxide drive physiological responses involved in cellular stress management, including apoptosis, autophagy, propagation of endoplasmic reticulum stress, cellular senescence, HIF1a signaling, and immune responses. They also affect cell proliferation, migration, differentiation, and the cell cycle. Filtering the huge literature on pathologies highlights strong experimental evidence that 30-40 pathologies may be driven by mitochondrial matrix superoxide or hydrogen peroxide. These can be grouped into overlapping and interacting categories: metabolic, cardiovascular, inflammatory, and neurological diseases; cancer; ischemia/reperfusion injury; aging and its diseases; external insults, and genetic diseases. Understanding the involvement of mitochondrial matrix superoxide and hydrogen peroxide concentrations in these diseases can facilitate the rational development of appropriate therapies.

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Mitochondrial Coenzyme Q Protects Sepsis-Induced Acute Lung Injury by Activating PI3K/Akt/GSK-3β/mTOR Pathway in Rats

Cited by 56 publications

References 34 publications

MitoQ protects against hyperpermeability of endothelium barrier in acute lung injury via a Nrf2-dependent mechanism

MitoQ protects against hyperpermeability of endothelium barrier in acute lung injury via a Nrf2-dependent mechanism

Sufentanil attenuates inflammation and oxidative stress in sepsis-induced acute lung injury by downregulating KNG1 expression

Riding the tiger – physiological and pathological effects of superoxide and hydrogen peroxide generated in the mitochondrial matrix

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