Signaling pathways of magnolol‐induced adrenal steroidogensis

Chen, Yung Chia; Chang, Ming-Fong; Chen, Ying; Wang, Seu‐Mei

doi:10.1016/j.febslet.2005.06.068

Cited by 12 publications

(9 citation statements)

References 47 publications

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“…Because of the potent biological actions of these cytokines, considerable attention has been focused on identifying the mechanisms that activate and limit cytokine gene expression. Only recently was it recognized that PA may signal through novel mechanisms, including the MAPK signaling network, which might be linked to transcription factor in the nucleus (Watanabe et al, 2004;Chen et al, 2005). Consistent with these findings, we and others have found that various kinases, including Akt and MAPKs can be activated by PA stimulation Lim et al, 2003;Li and Malik, 2005).…”

Section: Discussionsupporting

confidence: 74%

Janus Kinase-Signal Transducer and Activator of Transcription Mediates Phosphatidic Acid-Induced Interleukin (IL)-1β and IL-6 Production

Lee

Lim²,

Sakong³

et al. 2006

Molecular Pharmacology

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We have found previously that phosphatidic acid (PA) can induce inflammatory mediators such as cytokines, which implies that PA plays a role in inflammatory response. In the present study, we provide evidence of the PA-mediated activation of the Janus tyrosine kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, which results in the production of interleukin (IL)-1␤ and IL-6. PA elicited the rapid phosphorylations of JAK2 and STAT1/3, and the subsequent nuclear translocation. Macrophages that had been transiently transfected with a luciferase reporter construct containing eight consecutive ␥-interferon activating sequence (GAS) elements, a known STAT binding site, exhibited enhanced reporter gene activity in response to PA stimulation, which further supports the involvement of JAK-STAT activation in the PA-induced signaling pathway. Of the inflammatory cytokines, IL-1␤, IL-6, and tumor necrosis factor (TNF)-␣ were detected in media from macrophages stimulated with PA.Moreover, the JAK2 inhibitor ␣-cyano-(3,4-dihydroxy)-N-benzylcinnamide (AG-490) abolished PA-induced IL-1␤ and IL-6 release but not TNF-␣ production, which is consistent with the notion that IL-1␤ and IL-6 but not TNF-␣ contain a STAT binding element in their promoter region. The knockdown of JAK2 in macrophages by small interfering RNA significantly attenuated PA-induced IL-1␤ and IL-6 production. In addition, JAK2 inhibitor suppressed PA-induced Akt phosphorylation, and the Akt inhibitor 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) blocked GAS activation (GAS contains a promoter that responds to PA), suggesting that PA-mediated JAK2 activation leads to phosphatidylinositol 3-kinase/Akt phosphorylation and STAT activation, and the subsequent translocation of STAT to the nucleus. Together, our data demonstrate that PA-activated macrophages produce IL-1␤ and IL-6 and that these processes require the activation of the JAK2-STAT1/3 or JAK2-Akt-STAT signaling pathways.Phosphatidic acid (PA) is an important metabolite that is involved in phospholipid biosynthesis and membrane remodeling (Lim et al., 2003). PA can be generated by several cellular processes, such as the hydrolysis of phosphatidylcholine by phospholipase D, the phosphorylation of DAG by DAG kinase, and the acylation of lyso-PA by lyso-PA acyltransferase (Koch et al., 2004;van Baal et al., 2005), and can be metabolized to other bioactive lipids, such as lyso-PA and DAG (Nanjundan and Possmayer, 2003).It has been suggested that PA may play a crucial role in the regulation of various biological events. For example, PA is involved in the phosphorylations of many proteins Avila-Flores et al., 2005), activation because of oxidative stress (de Jong et al., 2004), modulation of membrane trafficking (Kooijman et al

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Section: Discussionsupporting

confidence: 74%

Janus Kinase-Signal Transducer and Activator of Transcription Mediates Phosphatidic Acid-Induced Interleukin (IL)-1β and IL-6 Production

Lee

Lim²,

Sakong³

et al. 2006

Molecular Pharmacology

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“…The inhibitors, AG490, LY-294002, and IBMX, were respectively diluted in DMSO for stock solutions of 1mg/ml, 5mg/ml, and 0.5 M. A G-CSF receptor chimera (Fc Chimera Active) was purchased from Abcam (Cambridge, MA), and G-CSF was obtained from Loma Linda University Pharmacy; both were diluted in phosphate buffered saline. The following concentrations were used: cholera toxin (50 ng/ml) (Hsu et al, 2006); AG490 (50 μM) (Chen et al, 2005); LY-294002 (20 μM) (Williams et al, 2010); and IBMX (10 μM) (Montero-Hadjadje et al, 2006). A dose-response study of G-CSF (using 30, 100, and 300 ng/ml) (Hsu et al, 2006), and the G-CSF receptor chimera (at 10, 30, and 100 ng/ml) after cholera toxin treatment was conducted.…”

Section: Methodsmentioning

confidence: 99%

Granulocyte-colony stimulating factor activates JAK2/PI3K/PDE3B pathway to inhibit corticosterone synthesis in a neonatal hypoxic-ischemic brain injury rat model

Charles

Perera

Doycheva

et al. 2015

Experimental Neurology

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Objective Our previous study demonstrated that granulocyte-colony stimulating factor (G-CSF)-induced neuroprotection is accompanied by an inhibition of corticosterone production in a neonatal hypoxic-ischemic (HI) rat model. The present study investigates how G-CSF inhibits corticosterone production, using adrenal cortical cells and HI rat pups. Methods Cholera toxin was used to induce corticosterone synthesis in a rodent Y1 adrenal cortical cell line by increasing cyclic adenosine monophosphate (cAMP). Both corticosterone and cAMP were quantitatively measured using a commercial enzyme-linked immunosorbent assay (ELISA). The downstream signaling components of the G-CSF receptor, including Janus Kinase 2 (JAK2)/Phosphatidylinositol-3-kinase (PI3K)/Protein kinase B (Akt) and Phosphodiesterase 3B (PDE3B), were detected by western blot. Sprague-Dawley rat pups at the age of 10 days (P10) were subjected to unilateral carotid artery ligation followed by hypoxia for 2.5 hours. Brain infarction volumes were determined using 2,3,5-triphenyltetrazoliumchloride monohydrate (TTC) staining. Results G-CSF at 30ng/ml inhibited corticosterone synthesis but lost its inhibitory effect at higher doses. The inhibitory effect of G-CSF was conferred by interfering with cAMP signaling via the activation of the JAK2/PI3K/PDE3B signaling pathway. The degradation of cAMP by G-CSF signaling reduced corticosterone production. This mechanism was further verified in the neonatal HI brain injury rat model, in which inhibition of PDE3B reversed the protective effects of G-CSF. Conclusion Our data suggest that the neuroprotective G-CSF reduces corticosterone synthesis at the adrenal level by degrading intracellular cAMP via activation of the JAK2/PI3K/PDE3B pathway.

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“…Animals were maintained according to the Guide for the Care and Use of Laboratory Animals set by Kaohsiung Medical University. Adrenal cell cultures were prepared as described by Chen, Chang, Chen, and Wang (2005). For the StAR promoter activity assay, Chinese hamster ovary cell line (CHO-K1) was used, which was kindly provided by Prof. Wen-Wei Chang (Chung-Shan Medical University, Taiwan).…”

Section: Cell Culturementioning

confidence: 99%

“…Cell viability was determined using the tetrazolium dye colorimetric test according to the procedure described by Chen et al (2005).…”

Section: Cell Viability Assaymentioning

confidence: 99%

Mechanism of Toona sinensis-stimulated adrenal steroidogenesis in primary rat adrenal cells

Chen

Liang

Huang

et al. 2015

Journal of Functional Foods

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Signaling pathways of magnolol‐induced adrenal steroidogensis

Cited by 12 publications

References 47 publications

Janus Kinase-Signal Transducer and Activator of Transcription Mediates Phosphatidic Acid-Induced Interleukin (IL)-1β and IL-6 Production

Janus Kinase-Signal Transducer and Activator of Transcription Mediates Phosphatidic Acid-Induced Interleukin (IL)-1β and IL-6 Production

Granulocyte-colony stimulating factor activates JAK2/PI3K/PDE3B pathway to inhibit corticosterone synthesis in a neonatal hypoxic-ischemic brain injury rat model

Mechanism of Toona sinensis-stimulated adrenal steroidogenesis in primary rat adrenal cells

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