Image2_Nuciferine induces autophagy to relieve vascular cell adhesion molecule 1 activation via repressing the Akt/mTOR/AP1 signal pathway in the vascular endothelium.tif

Pro-inflammatory factor-associated vascular cell adhesion molecule 1 (VCAM1) activation initiates cardiovascular events. This study aimed to explore the protective role of nuciferine on TNFα-induced VCAM1 activation. Nuciferine was administrated to both high-fat diet (HFD)-fed mice and the TNFα-exposed human vascular endothelial cell line. VCAM1 expression and further potential mechanism(s) were explored. Our data revealed that nuciferine intervention alleviated VCAM1 activation in response to both high-fat diet and TNFα exposure, and this protective effect was closely associated with autophagy activation since inhibiting autophagy by either genetic or pharmaceutical approaches blocked the beneficial role of nuciferine. Mechanistical studies revealed that Akt/mTOR inhibition, rather than AMPK, SIRT1, and p38 signal pathways, contributed to nuciferine-activated autophagy, which further ameliorated TNFα-induced VCAM1 via repressing AP1 activation, independent of transcriptional regulation by IRF1, p65, SP1, and GATA6. Collectively, our data uncovered a novel biological function for nuciferine in protecting VCAM1 activation, implying its potential application in improving cardiovascular events.</p

Image1_Nuciferine induces autophagy to relieve vascular cell adhesion molecule 1 activation via repressing the Akt/mTOR/AP1 signal pathway in the vascular endothelium.tif

Pro-inflammatory factor-associated vascular cell adhesion molecule 1 (VCAM1) activation initiates cardiovascular events. This study aimed to explore the protective role of nuciferine on TNFα-induced VCAM1 activation. Nuciferine was administrated to both high-fat diet (HFD)-fed mice and the TNFα-exposed human vascular endothelial cell line. VCAM1 expression and further potential mechanism(s) were explored. Our data revealed that nuciferine intervention alleviated VCAM1 activation in response to both high-fat diet and TNFα exposure, and this protective effect was closely associated with autophagy activation since inhibiting autophagy by either genetic or pharmaceutical approaches blocked the beneficial role of nuciferine. Mechanistical studies revealed that Akt/mTOR inhibition, rather than AMPK, SIRT1, and p38 signal pathways, contributed to nuciferine-activated autophagy, which further ameliorated TNFα-induced VCAM1 via repressing AP1 activation, independent of transcriptional regulation by IRF1, p65, SP1, and GATA6. Collectively, our data uncovered a novel biological function for nuciferine in protecting VCAM1 activation, implying its potential application in improving cardiovascular events.</p

Image3_Nuciferine induces autophagy to relieve vascular cell adhesion molecule 1 activation via repressing the Akt/mTOR/AP1 signal pathway in the vascular endothelium.tif

Pro-inflammatory factor-associated vascular cell adhesion molecule 1 (VCAM1) activation initiates cardiovascular events. This study aimed to explore the protective role of nuciferine on TNFα-induced VCAM1 activation. Nuciferine was administrated to both high-fat diet (HFD)-fed mice and the TNFα-exposed human vascular endothelial cell line. VCAM1 expression and further potential mechanism(s) were explored. Our data revealed that nuciferine intervention alleviated VCAM1 activation in response to both high-fat diet and TNFα exposure, and this protective effect was closely associated with autophagy activation since inhibiting autophagy by either genetic or pharmaceutical approaches blocked the beneficial role of nuciferine. Mechanistical studies revealed that Akt/mTOR inhibition, rather than AMPK, SIRT1, and p38 signal pathways, contributed to nuciferine-activated autophagy, which further ameliorated TNFα-induced VCAM1 via repressing AP1 activation, independent of transcriptional regulation by IRF1, p65, SP1, and GATA6. Collectively, our data uncovered a novel biological function for nuciferine in protecting VCAM1 activation, implying its potential application in improving cardiovascular events.</p

DataSheet1_Nuciferine induces autophagy to relieve vascular cell adhesion molecule 1 activation via repressing the Akt/mTOR/AP1 signal pathway in the vascular endothelium.docx

Pro-inflammatory factor-associated vascular cell adhesion molecule 1 (VCAM1) activation initiates cardiovascular events. This study aimed to explore the protective role of nuciferine on TNFα-induced VCAM1 activation. Nuciferine was administrated to both high-fat diet (HFD)-fed mice and the TNFα-exposed human vascular endothelial cell line. VCAM1 expression and further potential mechanism(s) were explored. Our data revealed that nuciferine intervention alleviated VCAM1 activation in response to both high-fat diet and TNFα exposure, and this protective effect was closely associated with autophagy activation since inhibiting autophagy by either genetic or pharmaceutical approaches blocked the beneficial role of nuciferine. Mechanistical studies revealed that Akt/mTOR inhibition, rather than AMPK, SIRT1, and p38 signal pathways, contributed to nuciferine-activated autophagy, which further ameliorated TNFα-induced VCAM1 via repressing AP1 activation, independent of transcriptional regulation by IRF1, p65, SP1, and GATA6. Collectively, our data uncovered a novel biological function for nuciferine in protecting VCAM1 activation, implying its potential application in improving cardiovascular events.</p

Overexpression of <i>CYP71Z2</i> suppressed the IAA signaling pathway in rice after inoculation with PXO99^A.

<p>(A) Quantification of free IAA in the leaves of <i>CYP71Z2</i>-overexpressing rice after inoculation at the ripening stage. Transcript levels of genes <i>AAO1</i> (B), <i>IAA1</i> (C) and <i>IAA20</i> (D) in <i>CYP71Z2</i>-overexpressing rice after inoculation were determined by qRT-PCR. Data represent means of three replicates ± standard deviation.</p

Knock-down <i>CYP71Z2</i> had no impact on <i>Xoo</i> resistance.

<p>(A) No significant difference in disease development was observed between <i>CYP71Z2</i>-RNAi lines and wild-type in response to inoculation of <i>Xoo</i> strain PXO99^A. (B) Expression levels of <i>CYP71Z2</i> in <i>CYP71Z2</i>-RNAi lines and wild-type. Data represent means of three replicates ± standard deviation.</p

Overexpressing <i>CYP71Z2</i> Enhances Resistance to Bacterial Blight by Suppressing Auxin Biosynthesis in Rice

<div><p>Background</p><p>The hormone auxin plays an important role not only in the growth and development of rice, but also in its defense responses. We’ve previously shown that the P450 gene <i>CYP71Z2</i> enhances disease resistance to pathogens through regulation of phytoalexin biosynthesis in rice, though it remains unclear if auxin is involved in this process or not.</p><p>Methodology and Principal Findings</p><p>The expression of <i>CYP71Z2</i> was induced by <i>Xanthomonas oryzae</i> pv. <i>oryzae</i> (<i>Xoo</i>) inoculation was analyzed by qRT-PCR, with GUS histochemical staining showing that <i>CYP71Z2</i> expression was limited to roots, blades and nodes. Overexpression of <i>CYP71Z2</i> in rice durably and stably increased resistance to <i>Xoo</i>, though no significant difference in disease resistance was detected between <i>CYP71Z2</i>-RNA interference (RNAi) rice and wild-type. Moreover, IAA concentration was determined using the HPLC/electrospray ionization/tandem mass spectrometry system. The accumulation of IAA was significantly reduced in <i>CYP71Z2</i>-overexpressing rice regardless of whether plants were inoculated or not, whereas it was unaffected in <i>CYP71Z2</i>-RNAi rice. Furthermore, the expression of genes related to IAA, expansin and SA/JA signaling pathways was suppressed in <i>CYP71Z2</i>-overexpressing rice with or without inoculation.</p><p>Conclusions and Significance</p><p>These results suggest that <i>CYP71Z2</i>-mediated resistance to <i>Xoo</i> may be via suppression of IAA signaling in rice. Our studies also provide comprehensive insight into molecular mechanism of resistance to <i>Xoo</i> mediated by IAA in rice. Moreover, an available approach for understanding the P450 gene functions in interaction between rice and pathogens has been provided.</p></div

Image4_Nuciferine induces autophagy to relieve vascular cell adhesion molecule 1 activation via repressing the Akt/mTOR/AP1 signal pathway in the vascular endothelium.tif

Pro-inflammatory factor-associated vascular cell adhesion molecule 1 (VCAM1) activation initiates cardiovascular events. This study aimed to explore the protective role of nuciferine on TNFα-induced VCAM1 activation. Nuciferine was administrated to both high-fat diet (HFD)-fed mice and the TNFα-exposed human vascular endothelial cell line. VCAM1 expression and further potential mechanism(s) were explored. Our data revealed that nuciferine intervention alleviated VCAM1 activation in response to both high-fat diet and TNFα exposure, and this protective effect was closely associated with autophagy activation since inhibiting autophagy by either genetic or pharmaceutical approaches blocked the beneficial role of nuciferine. Mechanistical studies revealed that Akt/mTOR inhibition, rather than AMPK, SIRT1, and p38 signal pathways, contributed to nuciferine-activated autophagy, which further ameliorated TNFα-induced VCAM1 via repressing AP1 activation, independent of transcriptional regulation by IRF1, p65, SP1, and GATA6. Collectively, our data uncovered a novel biological function for nuciferine in protecting VCAM1 activation, implying its potential application in improving cardiovascular events.</p

Overexpression of <i>CYP71Z2</i> inhibited the expression levels of genes involved in disease resistance pathway mediated by SA/JA.

<p>The expression levels of four genes <i>PR1a</i> (A), <i>PR1b</i> (B), <i>AOS2</i> (C) and <i>LOX</i> (D) functioning in the SA/JA-dependent disease resistance pathways in <i>CYP71Z2</i>-overexpressing rice plant. Data represent means of three replicates ± standard deviation.</p

Expression patterns of GUS driven by the <i>CYP71Z2</i> promoter in various organs and tissues of transgenic rice plant.

<p>Shown are leaf <b>(A)</b>, node <b>(C)</b>, lemma and palea <b>(D, F)</b>, primary root <b>(G)</b> and transverse section of a leaf <b>(B)</b> and node <b>(E)</b>. Scale bars are 400 μm <b>(A)</b>, 50 μm <b>(B, E)</b> and 1.2 mm <b>(C</b>, <b>D</b>, <b>F</b> and <b>G)</b>.</p