S‐Nitrosylation of Prostacyclin Synthase Instigates Nitrate Cross‐Tolerance <i>In Vivo</i>

Zhou, Shengnan; Lu, Jianrong; Wang, Xueqing; Shan, Mei-Rong; Zhang, Miao; Pan, Guopin; Xu, Jian; Li, Peng; Song, Ping; Pang, Xinyan; Bai, Yongping; Liu, Chao; Wang, Shuangxi

doi:10.1002/cpt.1094

Cited by 23 publications

(28 citation statements)

References 40 publications

(72 reference statements)

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“…In general, VitB6, in the form of PLP, is the coenzyme of 5 enzymes in these metabolic pathways: cystathionine‐β‐synthase, cystathionine‐γ‐lyase, cytoplasmic and mitochondrial serine hydroxymethyltransferase and glycine decarboxylase in the mitochondria . In this way, VitB6 regulates the transsulfuration pathway, which contributes to homocysteine regulation and provides cysteine synthesis . However, in this study, we reported that AMPK‐DOK3 pathway mediates VitB6’s actions of anti‐inflammation.…”

Section: Discussionmentioning

confidence: 66%

Vitamin B6 inhibits macrophage activation to prevent lipopolysaccharide‐induced acute pneumonia in mice

Shan

Zhou

et al. 2020

J Cellular Molecular Medi

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Macrophage activation participates in the pathogenesis of pulmonary inflammation. As a coenzyme, vitamin B6 (VitB6) is mainly involved in the metabolism of amino acids, nucleic acids, glycogen and lipids. We have previously reported that activation of AMP‐activated protein kinase (AMPK) produces anti‐inflammatory effects both in vitro and in vivo. Whether VitB6 via AMPK activation prevents pulmonary inflammation remains unknown. The model of acute pneumonia was induced by injecting mice with lipopolysaccharide (LPS). The inflammation was determined by measuring the levels of interleukin‐1 beta (IL‐1β), IL‐6 and tumour necrosis factor alpha (TNF‐α) using real time PCR, ELISA and immunohistochemistry. Exposure of cultured primary macrophages to VitB6 increased AMP‐activated protein kinase (AMPK) Thr172 phosphorylation in a time/dose‐dependent manner, which was inhibited by compound C. VitB6 downregulated the inflammatory gene expressions including IL‐1β, IL‐6 and TNF‐α in macrophages challenged with LPS. These effects of VitB6 were mirrored by AMPK activator 5‐aminoimidazole‐4‐carboxamide ribonucleoside (AICAR). However, VitB6 was unable to inhibit LPS‐induced macrophage activation if AMPK was in deficient through siRNA‐mediated approaches. Further, the anti‐inflammatory effects produced by VitB6 or AICAR in LPS‐treated macrophages were abolished in DOK3 gene knockout (DOK3−/−) macrophages, but were enhanced in macrophages if DOK3 was overexpressed. In vivo studies indicated that administration of VitB6 remarkably inhibited LPS‐induced both systemic inflammation and acute pneumonia in wild‐type mice, but not in DOK3−/− mice. VitB6 prevents LPS‐induced acute pulmonary inflammation in mice via the inhibition of macrophage activation.

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Section: Discussionmentioning

confidence: 66%

Vitamin B6 inhibits macrophage activation to prevent lipopolysaccharide‐induced acute pneumonia in mice

Shan

Zhou

et al. 2020

J Cellular Molecular Medi

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“…6 As a matter of fact, myocardial fibrosis is the end-points of cell differentiation, activation and proliferation of cardiac fibroblasts. 36,37 For example, microRNA (miR) comprises small, non-coding RNA that binds to a specific 3'-untranslated region of mRNA and inhibits mRNA translation or promotes mRNA degradation. As concerned to why Prrx2 F I G U R E 5 Cell differentiation induced by TGF-β is abolished by gene silence of Prrx2 in cardiac fibroblasts.…”

Section: F I G U R E 4 Tgf-β Induces Cell Differentiation and Up-regumentioning

confidence: 99%

“…The gene function may be regulated in transcriptional, post-transcriptional and post-translational levels. 36,37 For example, microRNA (miR) comprises small, non-coding RNA that binds to a specific 3'-untranslated region of mRNA and inhibits mRNA translation or promotes mRNA degradation. 38,39 It has been reported that Prrx2 mRNA is a target of miR-212-5p in breast cancer.…”

Section: F I G U R E 4 Tgf-β Induces Cell Differentiation and Up-regumentioning

confidence: 99%

Up‐regulation of paired‐related homeobox 2 promotes cardiac fibrosis in mice following myocardial infarction by targeting of Wnt5a

Bai

Tang

Shan

et al. 2019

J Cellular Molecular Medi

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Cardiac fibrosis is a key factor to determine the prognosis in patient with myocardial infarction (MI). The aim of this study is to investigate whether the transcriptional factor paired-related homeobox 2 (Prrx2) regulates Wnt5a gene expression and the role in myocardial fibrosis following MI. The MI surgery was performed by ligation of left anterior descending coronary artery. Cardiac remodelling was assessed by measuring interstitial fibrosis performed with Masson staining. Cell differentiation was examined by analysis the expression of alpha-smooth muscle actin (α-SMA). Both Prrx2 and Wnt5a gene expressions were up-regulated in mice following MI, accompanied with increased mRNA and protein levels of α-SMA, collagen I and collagen III, compared to mice with sham surgery. Adenovirus-mediated gene knock down of Prrx2 increased survival rate, alleviated cardiac fibrosis, decreased infarction sizes and improved cardiac functions in mice with MI. Importantly, inhibition of Prrx2 suppressed ischaemia-induced Wnt5a gene expression and Wnt5a signalling. In cultured cardiac fibroblasts, TGF-β increased gene expressions of Prrx2 and Wnt5a, and induced cell differentiations, which were abolished by gene silence of either Prrx2 or Wnt5a. S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Bai W-W, Tang Z-Y, Shan T-C, et al. Up-regulation of paired-related homeobox 2 promotes cardiac fibrosis in mice following myocardial infarction by targeting of Wnt5a.

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“…Isolated 14-3-3 proteins, as potential protein partners of PTGIS, can recognize the canonical phosphorylated motifs of PTGIS protein in predicted amino acid positions 24–36, 75–82, 200–206, 223–232 using the online server [36] (). Other ways of post-translational regulation of prostacyclin synthase activity have been described to occur via reversible or irreversible S-nitrosylation [35,37], as well as S-glutathionylation of Cys residues of PTGIS protein [38]. Thus, it can be speculated that isolation from testis tissue lysate of multifunctional protein glutaredoxin (GLRX) [39,40,41,42], as a potential protein partner of PTGIS, indicates a probable role of GLRX in the S-glutathionylation of PTGIS.…”

Section: Resultsmentioning

confidence: 99%

Affinity Isolation and Mass Spectrometry Identification of Prostacyclin Synthase (PTGIS) Subinteractome

Ершов

Mezentsev

Kopylov

et al. 2019

Biology

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Prostacyclin synthase (PTGIS; EC 5.3.99.4) catalyzes isomerization of prostaglandin H2 to prostacyclin, a potent vasodilator and inhibitor of platelet aggregation. At present, limited data exist on functional coupling and possible ways of regulating PTGIS due to insufficient information about protein–protein interactions in which this crucial enzyme is involved. The aim of this study is to isolate protein partners for PTGIS from rat tissue lysates. Using CNBr-activated Sepharose 4B with covalently immobilized PTGIS as an affinity sorbent, we confidently identified 58 unique proteins by mass spectrometry (LC-MS/MS). The participation of these proteins in lysate complex formation was characterized by SEC lysate profiling. Several potential members of the PTGIS subinteractome have been validated by surface plasmon resonance (SPR) analysis. SPR revealed that PTGIS interacted with full-length cytochrome P450 2J2 and glutathione S-transferase (GST). In addition, PTGIS was shown to bind synthetic peptides corresponding to sequences of for GSTA1, GSTM1, aldo-keto reductase (AKR1A1), glutaredoxin 3 (GLRX3) and histidine triad nucleotide binding protein 2 (HINT2). Prostacyclin synthase could potentially be involved in functional interactions with identified novel protein partners participating in iron and heme metabolism, oxidative stress, xenobiotic and drugs metabolism, glutathione and prostaglandin metabolism. The possible biological role of the recognized interaction is discussed in the context of PTGIS functioning.

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S‐Nitrosylation of Prostacyclin Synthase Instigates Nitrate Cross‐Tolerance In Vivo

Cited by 23 publications

References 40 publications

Vitamin B6 inhibits macrophage activation to prevent lipopolysaccharide‐induced acute pneumonia in mice

Vitamin B6 inhibits macrophage activation to prevent lipopolysaccharide‐induced acute pneumonia in mice

Up‐regulation of paired‐related homeobox 2 promotes cardiac fibrosis in mice following myocardial infarction by targeting of Wnt5a

Affinity Isolation and Mass Spectrometry Identification of Prostacyclin Synthase (PTGIS) Subinteractome

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