An IκBα phosphorylation inhibitor induces heme oxygenase-1(HO-1) expression through the activation of reactive oxygen species (ROS)–Nrf2–ARE signaling and ROS–PI3K/Akt signaling in an NF-κB-independent mechanism

Min, Kyoung‐jin; Lee, Jung Tae; Joe, Eun‐Hye; Kwon, Taeg Kyu

doi:10.1016/j.cellsig.2011.05.013

Cited by 81 publications

(46 citation statements)

References 57 publications

(58 reference statements)

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“…‫ء‬b represent statistically significant differences (p Ͻ 0.05) compared with 0 ng/ml LPS. transcription (Min et al, 2011). Compared with LPS alone, cotreatment of BV-2 cells with LPS and BAY 11-7082 attenuated IL-1␤ and IL-6 cytokine mRNA induction by approximately 75% (Fig.…”

Section: Resultsmentioning

confidence: 88%

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Inflammatory Regulation of ATP Binding Cassette Efflux Transporter Expression and Function in Microglia

Gibson

Hossain

Richardson

et al. 2012

J Pharmacol Exp Ther

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ATP-binding cassette (ABC) efflux transporters, including multidrug resistance protein 1 (Mdr1), breast cancer resistance protein (Bcrp), and multidrug resistance-associated proteins (Mrps) extrude chemicals from the brain. Although ABC transporters are critical for blood-brain barrier integrity, less attention has been placed on the regulation of these proteins in brain parenchymal cells such as microglia. Prior studies demonstrate that inflammation after lipopolysaccharide (LPS) treatment alters transporter expression in the livers of mice. Here, we sought to determine the effects of inflammation on the expression and function of transporters in microglia. To test this, the expression and function of ABC efflux transport proteins were quantified in mouse BV-2 microglial cells in response to activation with LPS. Intracellular retention of fluorescent rhodamine 123, Hoechst 33342, and calcein acetoxymethyl ester was increased in LPS-treated microglia, suggesting that the functions of Mdr1, Bcrp, and Mrps were decreased, respectively. LPS reduced Mdr1, Bcrp, and Mrp4 mRNA and protein expression between 40 and 70%. Conversely, LPS increased expression of Mrp1 and Mrp5 mRNA and protein. Immunofluorescent staining confirmed reduced Bcrp and Mrp4 and elevated Mrp1 and Mrp5 protein in activated microglia. Pharmacological inhibition of nuclear factor B (NF-B) transcriptional signaling attenuated down-regulation of Mdr1a mRNA and potentiated up-regulation of Mrp5 mRNA in LPS-treated cells. Together, these data suggest that LPS stimulates microglia and impairs efflux of prototypical ABC transporter substrates by altering mRNA and protein expression, in part through NF-B signaling. Decreased transporter efflux function in microglia may lead to the retention of toxic chemicals and aberrant cell-cell communication during neuroinflammation.

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Section: Resultsmentioning

confidence: 88%

“…One possible explanation is that BAY 11-7082 also acts independently of NF-B to activate Nrf2. In fact, BAY 11-7082 has been shown to increase mRNA and protein of Nrf2 responsive genes in a Nrf2-dependent manner in human colorectal cells, likely through production of reactive oxygen species (Min et al, 2011).…”

mentioning

confidence: 99%

Inflammatory Regulation of ATP Binding Cassette Efflux Transporter Expression and Function in Microglia

Gibson

Hossain

Richardson

et al. 2012

J Pharmacol Exp Ther

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“…In addition to being a requirement for Nrf2, increased Akt activity also elevates Nrf2 activity (48). Earlier it was found that in cancer cell lines gain of function of the PI3K/Akt pathway regulates Nrf2 (49). PI3K is activated by membrane receptor tyrosine kinase(s) and forms a complex with phosphotyrosine residues in the activator receptor.…”

Section: Discussionmentioning

confidence: 99%

Flavone-resistant Leishmania donovani Overexpresses LdMRP2 Transporter in the Parasite and Activates Host MRP2 on Macrophages to Circumvent the Flavone-mediated Cell Death

Chowdhury¹,

Mukhopadhyay

Saha³

et al. 2014

Journal of Biological Chemistry

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Background: Leishmania donovani adopts several defense mechanisms to become resistant to antileishmanial agents. Results: Laboratory-grown flavone (baicalein)-resistant parasites exhibit efflux of drug by LdABCC2 transporter. Inside the host macrophage, this parasite up-regulates host MRP2 transporter by an Nrf2-dependent pathway. Conclusion: Resistant Leishmania parasite exploits ABC transporter in the parasite and inside the host. Significance: The mechanism of drug resistance in clinical isolates can be probed.

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“…Silva et al (73) demonstrated that ROS mediate the phosphatase and tensin homolog (PTEN)-independent activation of the PI3K/Akt pathway in some T cell acute lymphoblastic leukemia (T-ALL) cells. Min et al suggested that ROS may activate PI3K/Akt and Nrf2 signaling (74). Thus, it can be hypothesized that apelin induces ROS production, activates PI3K/Akt, and ultimately, exerts anti-apoptotic and neroprotective effects.…”

Section: Apelin Protects the Central Nervous System By Stimulating Romentioning

confidence: 99%

Apelin/APJ system: A novel therapeutic target for oxidative stress-related inflammatory diseases (Review)

Zhou

Cao

Chen

2016

International Journal of Molecular Medicine

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Abstract. Apelin, the endogenous ligand of APJ which is a member of G protein-coupled receptors, has been shown to be expressed in a variety of tissues in vivo and to exert significant biological effects. Studies have indicated that the apelin/APJ system is involved in the regulation of a variety of physiological functions and pathological processes, and that it is associated with cardiovascular diseases (such as atherosclerosis, hypertension, heart failure and myocardial injury), diabetes with microvascular complications, ischemia reperfusion injury, tumors, pre-eclampsia, as well as others. The occurrence of these diseases is closely related to endothelial dysfunction and the local inflammatory response; however, the occurrence of oxidative stress is related to vascular injury, due to the excessive generation of reactive oxygen species (ROS) and can lead to vascular damage and a series of inflammatory reactions. Therefore, this review summarizes the association between apelin/APJ, oxidative stress and inflammation-related diseases. In addition, drugs targeting the apelin/APJ system are recommended, thus providing a novel therapeutic strategy for oxidative stress-related inflammatory diseases.

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An IκBα phosphorylation inhibitor induces heme oxygenase-1(HO-1) expression through the activation of reactive oxygen species (ROS)–Nrf2–ARE signaling and ROS–PI3K/Akt signaling in an NF-κB-independent mechanism

Cited by 81 publications

References 57 publications

Inflammatory Regulation of ATP Binding Cassette Efflux Transporter Expression and Function in Microglia

Inflammatory Regulation of ATP Binding Cassette Efflux Transporter Expression and Function in Microglia

Flavone-resistant Leishmania donovani Overexpresses LdMRP2 Transporter in the Parasite and Activates Host MRP2 on Macrophages to Circumvent the Flavone-mediated Cell Death

Apelin/APJ system: A novel therapeutic target for oxidative stress-related inflammatory diseases (Review)

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