4-Ketopinoresinol, a novel naturally occurring ARE activator, induces the Nrf2/HO-1 axis and protects against oxidative stress-induced cell injury via activation of PI3K/AKT signaling

Chen, Huang-Hui; Chen, Yu-Tsen; Huang, Yen-Wen; Tsai, Hui‐Ju; Kuo, Ching‐Chuan

doi:10.1016/j.freeradbiomed.2011.12.012

Cited by 126 publications

(86 citation statements)

References 58 publications

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“…Therefore, further studies are required to clarify the role of the Nrf2/ARE pathway in the HO-1/CO system in regulating the balance of mitochondrial fusion/fission. Ultimately, the P38 mitogen associated protein kinase, extracellular signal regulated kinase and protein kinase C signaling pathways had been reported to mediate the induction of HO-1 (39). Hence, to identify which signaling cascades other than the PI3K/Akt pathway facilitated the cytoprotective effects of HO-1/CO system against oxidative cellular injury requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Phosphatidylinositol 3‑kinase‑mediated HO‑1/CO represses Fis1 levels and alleviates lipopolysaccharide‑induced oxidative injury in alveolar macrophages

Shi

Zhang

et al. 2018

Exp Ther Med

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Abstract. Sepsis-related acute respiratory distress syndrome is characterized by marked oxidative stress and mitochondrial dysfunction lacking of specific therapy. Heme oxygenase (HO)-1 followed by endogenous carbon monoxide (CO) exerted a cytoprotective effect against multi-organ damage during sepsis. Additionally, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, which serves as an upstream regulator of HO-1, was associated with inflammation and oxidative stress. Therefore, the purpose of the present study was to investigate whether the PI3K/Akt pathway was involved in the effects of HO-1/CO on the expression of mitochondrial fission 1 protein (Fis1). In the present study, CO releasing molecule-2 (CORM2), as the exogenous source of CO, plus LY294002, as a specific PI3K inhibitor, were pre-incubated in lipopolysaccharide (LPS)-simulated rat NR8383 alveolar macrophages. The results demonstrated that CORM2 improved cell viability, inhibited tumor necrosis factor-α levels, malondialdehyde contents, while elevating interleukin-10 levels and superoxide dismutase activities. In addition, pretreatment with CORM2 suppressed the fragmentation of mitochondria, upregulated the expressions of phosphorylated-Akt and HO-1 but downregulated the levels of Fis1 mRNA and protein in LPS-exposed cells. However, pretreatment with LY294002 significantly inhibited the phosphorylation of Akt, decreased HO-1 levels, aggravated mitochondrial fragmentation, increased Fis1 mRNA and protein levels, and reversed the above protective effects of CORM2. Collectively, the results of the present study indicated that the PI3K/Akt pathway mediated the cytoprotective effects of HO-1/CO on the transcription and translational levels of Fis1, and alleviated LPS-induced oxidative injury in alveolar macrophages.

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Section: Discussionmentioning

confidence: 99%

Phosphatidylinositol 3‑kinase‑mediated HO‑1/CO represses Fis1 levels and alleviates lipopolysaccharide‑induced oxidative injury in alveolar macrophages

Shi

Zhang

et al. 2018

Exp Ther Med

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“…A recent study indicated that the PI3K/Akt pathway also has a role in HO-1 regulation. For example, Chen et al (29) found that 4-ketopinoresinol, a novel naturally occurring ARE activator, induces activation of the Nrf2/HO-1 axis and protects against oxidative stress-induced cell injury via activation of PI3K/Akt signaling. PI3K, a lipid kinase, can be activated to generate the lipid second messenger PIP3 and subsequently activates its main downstream effector, the serine/threonine kinase Akt, which phosphorylates a variety of substrates that function to suppress apoptosis and promote progression through the cell cycle (30).…”

Section: Discussionmentioning

confidence: 99%

Post-conditioning with sevoflurane induces heme oxygenase-1 expression via the PI3K/Akt pathway in lipopolysaccharide-induced acute lung injury

Zhao

Wu²,

Zhang

et al. 2014

Molecular Medicine Reports

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Abstract. The aim of the present study was to explore the regulatory mechanism of heme oxygenase-1 (HO-1) expression induced by sevoflurane (Sevo) in lipopolysaccharide (LPS)-induced acute lung injury (ALI). Sprague-Dawley rats were divided randomly into six groups: (A) Control, (B) 2.4% Sevo only, (C) LY294002 (PI3K inhibitor) only, (D) LPS + 2.4% Sevo, (E) LY294002 + LPS + 2.4% Sevo and (F) LPS only. The pathological changes in wet/dry weight ratio (W/D), the activities of superoxide dismutase, myeloperoxidase (MPO), malondialdehyde, and HO-1, as well as the expression of intercellular adhesion molecule (ICAM-1), HO-1, phospho-phosphatidylinositol 3-kinase (pPI3K) and phospho-Akt (pAkt) were recorded. Sevo post-conditioning was able to effectively protect from ALI with decreasing pathomorphological scores, MPO activity, W/D and the mRNA and protein expression levels of ICAM-1. Sevo promotes HO-1 expression via the PI3K/protein kinase B (PI3K/Akt) pathway with activation of pPI3K and pAkt. Inhibition of the PI3K/Akt pathway by LY294002 partly eliminates the protective effects of Sevo. It is concluded that Sevo post-conditioning has a vital role in inducing the upregulation of HO-1 expression via the PI3K/Akt pathway to alleviate ALI.

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“…pathway, they can supress it via several kinase inhibitors (without phosphorylation, Nrf2 is retained in the cytosol with Keap1) (ref. 93 ), Maf-lacking 81 , selective bZip domain complex inhibitors (impede interaction between Nrf2 -ARE interaction) (ref. 90 ) and RNA interference (Nrf2 translation blocking) (ref.…”

Section: Nrf2 Inhibitorsmentioning

confidence: 99%

“…90 ) and RNA interference (Nrf2 translation blocking) (ref. 93 ). However, there are not many Nrf2 inhibitors yet and because some cancer cells exploit the upregulation of the Nrf2-ARE pathway for easier survival, screening for substances with a suppressive effect is now in the interest of scientists 90 .…”

Section: Nrf2 Inhibitorsmentioning

confidence: 99%

Models for the study of skin wound healing. The role of Nrf2 and NF-κB

Ambrožová¹,

Ulrichová²,

Galandáková³

2017

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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a,bNrf2 and NF-κB transcription factors act in wound healing via their anti-inflammatory and anti-oxidant effects or through the immune response. Studying this process is a matter of some importance given the high cost of wound treatment. A major contribution in this regard is being made by models that enable investigation of the involvement of multiple factors in wound healing and testing new curative substances. This literature review was carried out via searches in the PubMed and Web of Science databases up to 2016. It covers skin wound healing, available models for its study (part I), the role of Nrf2 and NF-κB, substances that influence them and whether they can be used as markers (part II). Was found that in vitro assays are used for their availability but a holistic view must be established in vivo. In silico approaches are facilitating assessment of a vast amount of research data. Nfr2 and NF-κB play a crucial and reciprocal role in wound healing. Nrf2 controls repair-associated inflammation and protects against excessive accumulation of ROS while Nf-κB activates the innate immune reaction, proliferation and migration of cells, modulates expression of matrix metalloproteinases, secretion and stability of cytokines and growth factors for wound healing.

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4-Ketopinoresinol, a novel naturally occurring ARE activator, induces the Nrf2/HO-1 axis and protects against oxidative stress-induced cell injury via activation of PI3K/AKT signaling

Cited by 126 publications

References 58 publications

Phosphatidylinositol 3‑kinase‑mediated HO‑1/CO represses Fis1 levels and alleviates lipopolysaccharide‑induced oxidative injury in alveolar macrophages

Phosphatidylinositol 3‑kinase‑mediated HO‑1/CO represses Fis1 levels and alleviates lipopolysaccharide‑induced oxidative injury in alveolar macrophages

Post-conditioning with sevoflurane induces heme oxygenase-1 expression via the PI3K/Akt pathway in lipopolysaccharide-induced acute lung injury

Models for the study of skin wound healing. The role of Nrf2 and NF-κB

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