Influence of SkQ1 on expression of Nrf2 gene, ARE-controlled genes of antioxidant enzymes and their activity in rat blood leukocytes under oxidative stress

Vnukov, V. V.; Gutsenko, O. I.; Milutina, N. P.; Корниенко, И. В.; Ananyan, A. A.; Даниленко, А. О.; Panina, Svetlana; Plotnikov, Andrey A.; Makarenko, Maksim

doi:10.1134/s0006297915120081

Cited by 8 publications

(4 citation statements)

References 27 publications

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“…Nrf2 expression in leukocytes has been described in a few in vitro studies ( 21 , 22 ). In this study, to identify the potential role of Nrf2 in the HS-induced inflammatory response, the expression pattern of Nrf2 in leukocytes was investigated.…”

Section: Resultsmentioning

confidence: 99%

Protective role of nuclear factor erythroid 2-related factor 2 in the hemorrhagic shock-induced inflammatory response

Zhao

Hao

et al. 2016

International Journal of Molecular Medicine

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Hemorrhagic shock (HS) following trauma or major surgery significantly contributes to mortality. However, the mechanisms through which HS activates the inflammatory response are not yet fully understood. Nuclear factor-erythroid 2 (NF-E2) p45-related factor-2 (Nrf2), a bZIP transcription factor, is a master regulator of robust cytoprotective defenses. The present study investigated the role of Nrf2 in the pathophysiology of HS. Nrf2 expression in peripheral leukocytes obtained from patients with surgery-associated hemorrhage subjected to resuscitation treatment (termed HS patients) or healthy donors was examined by RT-qPCR. A marked increase in Nrf2 expression was detected in the leukocytes obtained from the HS patients, which indicates a correlation between Nrf2 expression and the development of HS. Wild-type (WT; Nrf2+/+) and Nrf2-deficient [Nrf2−/− or Nrf2-knockout (KO)] mice were subjected to surgery to induce HS. Systemic inflammation was significantly elevated in the Nrf2-KO mice compared with the WT mice following HS, as assessed by an increase in serum cytokine levels [interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-1β], as well as high-mobility group box 1 protein (HMGB1) expression. The Nrf2-KO mice exhibited more severe lung and liver injury following HS as evidenced by increased tissue damage, increased myeloperoxidase (MPO) activity and the increased production of pro-inflammatory cytokines. Additionally, Nrf2 deficiency augmented cytokine production induced by the exposure of peritoneal mouse macrophages to lipopolysaccha-ride (LPS) following HS. Taken together, these results suggest that Nrf2 is a critical host factor which limits immune dysregulation and organ injury following HS.

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Section: Resultsmentioning

confidence: 99%

Protective role of nuclear factor erythroid 2-related factor 2 in the hemorrhagic shock-induced inflammatory response

Zhao

Hao

et al. 2016

International Journal of Molecular Medicine

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“…Our data are generally consistent with previously published indirect data on the possible activation of the Keap1-Nrf2 signaling pathway by SkQ1. In particular, it was reported that the expression of genes of the antioxidant system (Sod1-2, Cat and Gpx4) increased after pre-treatment with SkQ1 under hypoxic conditions [22].…”

Section: Discussionmentioning

confidence: 99%

“…The protective effect of SkQ1 during oxidative stress can probably be realized not only through direct antioxidant activity but also as a result of activation of the Keap1/Nrf2/ARE signaling pathway [22]. In order to investigate the possible activation of the NRF2 transcription factor by SkQ1, we examined the level of NRF2 and NQO1 (NAD(P)H quinone dehydrogenase-1), an NRF2 target gene, in the liver of uninfected and infected animals (Figure 6).…”

Section: Nrf2 and Nqo1mentioning

confidence: 99%

Plastoquinone-Derivative SkQ1 Improved the Biliary Intraepithelial Neoplasia during Liver Fluke Infection

Zaparina,

Kovner,

Petrova

et al. 2024

CIMB

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Carcinogenic food-borne liver fluke infections are a serious epidemiological threat worldwide. The major complications of Opisthorchis felineus infection are chronic inflammation and biliary intraepithelial neoplasia. Although evidence has accumulated that increased reactive oxygen species production is observed in liver fluke infection, a direct relationship between the oxidative stress and biliary intraepithelial neoplasia has not been shown. Quinones and SkQ1, a derivative of plastoquinone, have been demonstrated to be cytoprotective in numerous liver injuries due to their potent antioxidant properties. This study is aimed to assess the level of biliary intraepithelial neoplasia in O. felineus-infected hamsters after treatment with mitochondria-targeted SkQ1. SkQ1 significantly reduced the biliary intraepithelial neoplasia, which was accompanied by a decrease in lipid and DNA oxidation byproducts, mRNA expression and level of proteins associated with inflammation (TNF-α, CD68) and fibrogenesis (CK7, αSMA), and was also associated with an activation of the Keap1-Nrf2 pathway. Thus, a direct relationship was found between oxidative stress and the severity of biliary intraepithelial neoplasia in O. felineus-infected hamsters. The hepatoprotective effect of plastoquinone-derivative SkQ1 was established; therefore, this compound is a promising agent in complex therapy in the treatment of opisthorchiasis.

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“…Furthermore, GST was previously shown to be activated by Nrf2 in response to oxidative stresses caused by xenobiotics (Chen et al 2018). Moreover, Nrf2 has been previously shown to elevate the transcriptional activity of the target genes encoding antioxidant enzymes like GPX4 (Vnukov et al 2015). Phosphorylated H2AX induced by ATM (called γH2AX) has been implicated in the damage repair processes responding to DNA double-strand breaks, indicating the potential of γH2AX as a promising molecular marker of DNA damage (Siddiqui et al 2015).…”

Section: Discussionmentioning

confidence: 99%

miRNA-155 silencing reduces sciatic nerve injury in diabetic peripheral neuropathy

Chen

Liu

et al. 2019

Journal of Molecular Endocrinology

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Neuropathic pain represents one of the most common complications associated with diabetes mellitus (DM) that impacts quality of life. Accumulating studies have highlighted the involvement of miRNAs in DM. Thus, the current study aimed to investigate the roles of miR-155 in diabetic peripheral neuropathy (DPN). In vitro DPN models were established using rat Schwann cells (SCs) by treatment with 5.5 mM glucose. Gain- or loss-of-function studies were conducted to determine the effect of miR-155 on Nrf2, cellular function, reactive oxygen species and inflammation. Rat DNP models were established by streptozotocin injection and damage of sciatic nerve. Next, miR-155 antagomir or agomir was employed to investigate the effects associated with miR-155 on motor and sciatic nerve conduction velocity (MNCV, SNCV), angiogenesis and inflammatory response in vivo. Nrf2 was identified to be a target of miR-155 by dual-luciferase reporter gene assay. Silencing of miR-155 or restoration of Nrf2 promoted cell proliferation, inhibited apoptosis and alleviated inflammation in vitro. miR-155 antagomir-induced inhibition increased MNCV and SNCV, strengthened angiogenesis and alleviated inflammation in DPN rats. Additionally, the effects exerted by miR-155 were reversed when Nrf2 was restored both in vitro and in vivo. Taken together, the key findings of our study provide evidence indicating that miR-155 targeted and suppressed Nrf2 in DPN. miR-155 silencing was found to alleviate sciatic nerve injury in DPN, highlighting its potential as a therapeutic target for DPN.

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Influence of SkQ1 on expression of Nrf2 gene, ARE-controlled genes of antioxidant enzymes and their activity in rat blood leukocytes under oxidative stress

Cited by 8 publications

References 27 publications

Protective role of nuclear factor erythroid 2-related factor 2 in the hemorrhagic shock-induced inflammatory response

Protective role of nuclear factor erythroid 2-related factor 2 in the hemorrhagic shock-induced inflammatory response

Plastoquinone-Derivative SkQ1 Improved the Biliary Intraepithelial Neoplasia during Liver Fluke Infection

miRNA-155 silencing reduces sciatic nerve injury in diabetic peripheral neuropathy

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