Molecular cloning and characterization of novel human JNK2 (MAPK9) transcript variants that show different stimulation activities on AP-1

( Ping Zhang Wang ),( Ying Xiong ),( Chuan Ma ),( Tai Ping Shi ),( Da Long Ma ) 생화학분자생물학회 (구 한국생화학분자생물학회) 2010 BMB Reports Vol.43 No.11

The c-Jun NH2-terminal kinase (JNK) signaling pathway participates in many physiological functions. In the current study we reported the cloning and characterization of five novel JNK2 transcript variants, which were designated as JNK2 α3, JNK2 α4, JNK2 β3, JNK2 γ1 and JNK2 γ2, respectively. Among them, JNK2 α4 and JNK2 γ2 are potential non-coding RNA because they contain pre-mature stop codons. Both JNK2α3 and JNK2β3 contain an intact kinase domain, and both encode a protein product of 46 kDa, the same as those of JNK2α1 and JNK2β1. JNK2γ1 contains a disrupted kinase domain and it showed a disable function. When over-expressed in mammalian cells, JNK2α3 showed higher activity on AP-1 than that of JNK2β3 and JNK2γ1. Furthermore, JNK2α3 and JNK2β3 showed different levels of substrate phosphorylation, although they both could promote the proliferation of 293T cells. Our results further demonstrate that JNK2 isoforms preferentially target different substrates and may regulate the expression of various target genes. [BMB reports 2010; 43(11): 738-743]

Regulation of meilingmycin in Streptomyces nanchangensis: Effect of ammonium ion

Ying-ping Zhuang,Yong Wang,Ping Wang,Ju Chu,Si-liang Zhang 한국화학공학회 2010 Korean Journal of Chemical Engineering Vol.27 No.3

Effects of different ammonium sulfate concentrations on meilingmycin biosynthesis were studied in this research. The results show that a lower concentration of ammonium ions stimulates the biosynthesis of meilingmycin,while a concentration higher than 5mmol/L inhibits the mycelial growth and the biosynthesis of the products. However,increased sugar consumption rate with the elevated concentration of ammonium sulfate was observed during the fermentation process. On this basis, six enzymes, which are responsible for the meilingmycin biosynthesis and the glucose metabolism, were measured and analyzed during the bioprocess. The results suggest that glucose-6-phosphate dehydrogenase, citrate synthase, succinate dehydrogenase and fatty acid synthase are stimulated by higher concentration of ammonium ions, while valine dehydrogenase and methylmalonyl-CoA carboxyltransferase are inhibited. From the results it follows that the precursor supply was restricted with the higher concentration of ammonium ions, which results in the lower production of meilingmycin. Thus, the strategy of maintaining a low level of FAS activity is a critical factor for high yield of meilingmycin.

Rapid characterization of ginsenosides in the roots and rhizomes of Panax ginseng by UPLC-DAD-QTOF-MS/MS and simultaneous determination of 19 ginsenosides by HPLC-ESI-MS

Wang, Hong-Ping,Zhang, You-Bo,Yang, Xiu-Wei,Zhao, Da-Qing,Wang, Ying-Ping The Korean Society of Ginseng 2016 Journal of Ginseng Research Vol.40 No.4

Background: Ginsenosides are the characteristic and principal components which manifest a variety of the biological and pharmacological activities of the roots and rhizomes of Panax ginseng (GRR). This study was carried out to qualitatively and quantitatively determine the ginsenosides in the cultivated and forest GRR. Methods: A rapid and sensitive ultra-high-performance liquid chromatography coupled with diode-array detector and quadrupole/time of flight tandem mass spectrometry (UPLC-DAD-QTOF-MS/MS) was applied to the qualitative analysis of ginsenosides and a 4000 QTRAP triple quadrupole tandem mass spectrometer (HPLC-ESI-MS) was applied to quantitative analysis of 19 ginsenosides. Results: In the qualitative analysis, all ingredients were separated in 10 min. A total of 131 ginsenosides were detected in cultivated and forest GRR. The method for the quantitative determination was validated for linearity, precision, and limits of detection and quantification. 19 representative ginsenosides were quantitated. The total content of all 19 ginsenosides in the forest GRR were much higher than those in the cultivated GRR, and were increased with the growing ages. Conclusion: This newly developed analysis method could be applied to the quality assessment of GRR as well as the distinction between cultivated and forest GRR.

Association of Matrix Metalloproteinase (MMP)-2 and -9 Expression with Extra-gastrointestinal Stromal Tumor Metastasis

Wang, Chao,Ma, Hong-Xi,Jin, Mei-Shan,Zou, Ya-Bin,Teng, Yong-Liang,Tian, Zhuang,Wang, Hai-Ying,Wang, Yin-Ping,Duan, Xiu-Mei Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.10

Matrix metalloproteinase (MMP)-2 and MMP-9 are important proteases involved in invasion and metastasis of various tumors. Extra-gastrointestinal stromal tumors (EGISTs) are rare neoplasms. This study was performed to assess MMP-2 and MMP-9 expression in EGIST tissue samples for association with clinicopathological data from the patients. Twenty-one surgical EGIST tissue specimens were collected for analysis of MMP-2 and MMP-9 expression using immunohistochemistry. MMP-2 and MMP-9 proteins were expressed in all of the epithelial cell types of EGISTs, whereas they were only expressed in 75% of the spindle cell type, although there was no statistically significant difference (p>0.05). Expression of MMP-2 and MMP-9 proteins was associated with tumor size, mitotic rate, tumor necrosis, and distant metastasis (p<0.05). MMP-2 expression was linked with MMP-9 levels (p<0.05). However, there was no correlation between MMP-9 expression and age, sex, primary site, or cell morphology in any of these 21 EGIST patients (p>0.05). Moreover, expression of MMP-2 and MMP-9 proteins increased with the degree of EGIST risk. This study provided evidence of an association of MMP-2 and MMP-9 expression with advanced EGIST behavior.

Studies on the Genesis of Ginseng Rust Spots

YinG Ping Wang,Zhi Hong Li,Yan Jun Sun,Shi Wei Guo,Shuz Hen Tian,Liu Zhaorong 고려인삼학회 1997 Journal of Ginseng Research Vol.21 No.2

Complete ¹H-NMR and <SUP>13</SUP>C-NMR spectral assignment of five malonyl ginsenosides from the fresh flower buds of Panax ginseng

Yu-Shuai Wang,Yin-Ping Jin,Wei Gao,Sheng-Yuan Xiao,Yu-Wei Zhang,Pei-He Zheng,Jia Wang,Jun-Xia Liu,Cheng-He Sun,Ying-Ping Wang 고려인삼학회 2016 Journal of Ginseng Research Vol.40 No.3

Background: Ginsenosides are the major effective ingredients responsible for the pharmacological effects of ginseng. Malonyl ginsenosides are natural ginsenosides that contain a malonyl group attached to a glucose unit of the corresponding neutral ginsenosides. Methods: Medium-pressure liquid chromatography and semipreparative high-performance liquid chromatography were used to isolate purified compounds and their structures determined by extensive one-dimensional- and two-dimensional nuclear magnetic resonance (NMR) experiments. Results: A new saponin, namely malonyl-ginsenoside Re, was isolated from the fresh flower buds of Panax ginseng, along with malonyl-ginsenosides Rb1, Rb2, Rc, Rd. Some assignments for previously published ¹H- and <SUP>13</SUP>C-NMR spectra were found to be inaccurate. Conclusion: This study reports the complete NMR assignment of malonyl-ginsenoside Re, Rb₁, Rb₂, Rc, and Rd for the first time.

CYP1A1 Genetic Polymorphisms and Risk for Esophageal Cancer: a Case-control Study in Central China

Yun, Yu-Xia,Wang, Yan-Ping,Wang, Peng,Cui, Li-Hong,Wang, Kai-Juan,Zhang, Jian-Ying,Dai, Li-Ping Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

The purpose of this study was to evaluate the associations of CYP1A1 genetic polymorphisms with the risk of developing esophageal cancer (EC). A case-control study was carried out in a Chinese population in which 157 hospital based EC cases and 157 population based healthy controls with 1:1 match by age and sex were included. PCR based restriction fragment length polymorphisms (PCR-RFLP) were used to detect genotypes in case and control groups. For the CYP1A1 Ile/Val polymorphism, comparing with wild genotype Ile/Ile, both the heterozygote genotype Ile/Val and the combined variant genotype Ile/Val+Val/Val increased the risk of esophageal cancer (OR: 2.05, 95%CI: 1.19-3.54, OR: 1.86, 95%CI: 1.11-3.12). No significant association was found between the CYP1A1 MspI polymorphism and EC. According to analysis of combined genotypes, the TC/AG combined genotype which contained both variant alleles of these two polymorphisms increased the risk of developing EC (OR: 2.12, 95%CI: 1.16-3.85). Our results suggested that genetic polymorphisms of CYP1A1 may increase the susceptibility to EC.

RTN4 3'-UTR Insertion/Deletion Polymorphism and Susceptibility to Non-Small Cell Lung Cancer in Chinese Han Population

Lu, De-Yi,Mao, Xu-Hua,Zhou, Ying-Hui,Yan, Xiao-Long,Wang, Wei-Ping,Zheng, Ya-Biao,Xiao, Juan-Juan,Zhang, Ping,Wang, Jian-Guo,Ashwani, Neetika,Ding, Wei-Liang,Jiang, Hua,Shang, Yan,Wang, Ming-Hua Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

Nogo protein, encoded by gene reticulon-4 (RTN4), includes three major isoforms by different splicing, named Nogo-A Nogo-B and Nogo-C. Nogo proteins play an important role in the apoptosis of cells, especially in tumor cells. RTN4 single nucleotide polymorphisms (SNPs) can influence the efficiency of transcription and translation thus being related with an individual's predisposition to cancer. The CAA insertion/deletion polymorphism (rs34917480) within RTN4 3'-UTR has been reported to be associated with many cancer types. In order to investigate the relationship between this polymorphism and susceptibility to non-small cell lung cancer (NSCLC) in the Chinese population, we conducted the present case-control study including 411 NSCLC patients and 471 unrelated healthy controls. The genotype distributions were significantly different between cases and controls (p=0.014). We found that the del allele could significantly increase NSCLC risk (ins/ins vs ins/del: p=0.007, OR 1.46, 95%CI=1.11-1.93; dominant model: p=0.004, OR 1.47, 95%CI=1.13-1.92 and allele model: p=0.008, OR 1.35, 95%CI=1.08-1.67). This association was stronger in participants over 60 years old, males and smokers. We therefore conclude that the CAA insertion/deletion polymorphism (rs34917480) contributes to non-small cell lung cancer risk in Chinese population. Age, sex and environmental exposure are also related to carcinogenic effects of rs34917480.

Ginsenoside Rk1 ameliorates paracetamol-induced hepatotoxicity in mice through inhibition of inflammation, oxidative stress, nitrative stress and apoptosis

Hu, Jun-Nan,Xu, Xing-Yue,Li, Wei,Wang, Yi-Ming,Liu, Ying,Wang, Zi,Wang, Ying-Ping The Korean Society of Ginseng 2019 Journal of Ginseng Research Vol.43 No.1

Background: Frequent overdose of paracetamol (APAP) has become the major cause of acute liver injury. The present study was designed to evaluate the potential protective effects of ginsenoside Rk1 on APAP-induced hepatotoxicity and investigate the underlying mechanisms for the first time. Methods: Mice were treated with Rk1 (10 mg/kg or 20 mg/kg) by oral gavage once per d for 7 d. On the 7th d, allmice treated with 250mg/kg APAP exhibited severeliverinjury after 24 h, and hepatotoxicitywas assessed. Results: Our results showed that pretreatment with Rk1 significantly decreased the levels of serum alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor, and interleukin-$1{\beta}$ compared with the APAP group. Meanwhile, hepatic antioxidants, including superoxide dismutase and glutathione, were elevated compared with the APAP group. In contrast, a significant decrease in levels of the lipid peroxidation product malondialdehyde was observed in the ginsenoside Rk1-treated group compared with the APAP group. These effects were associated with a significant increase of cytochrome P450 E1 and 4-hydroxynonenal levels in liver tissues. Moreover, ginsenoside Rk1 supplementation suppressed activation of apoptotic pathways by increasing Bcl-2 and decreasing Bax protein expression levels, which was shown using western blotting analysis. Histopathological observation also revealed that ginsenoside Rk1 pretreatment significantly reversed APAP-induced necrosis and inflammatory infiltration in liver tissues. Biological indicators of nitrative stress, such as 3-nitrotyrosine, were also inhibited after pretreatment with Rk1 compared with the APAP group. Conclusion: The results clearly suggest that the underlying molecular mechanisms in the hepatoprotection of ginsenoside Rk1 in APAP-induced hepatotoxicity may be due to its antioxidation, antiapoptosis, anti-inflammation, and antinitrative effects.

Ginsenoside Rk1 ameliorates paracetamol-induced hepatotoxicity in mice through inhibition of inflammation, oxidative stress, nitrative stress and apoptosis

Jun-Nan Hu,Xing-Yue Xu,Wei Li,Yi-Ming Wang,Ying Liu,Zi Wang,Ying-Ping Wang 고려인삼학회 2019 Journal of Ginseng Research Vol.43 No.1

Background: Frequent overdose of paracetamol (APAP) has become the major cause of acute liver injury. The present study was designed to evaluate the potential protective effects of ginsenoside Rk1 on APAPinduced hepatotoxicity and investigate the underlying mechanisms for the first time. Methods: Micewere treated with Rk1 (10 mg/kg or 20 mg/kg) by oral gavage once per d for 7 d. On the 7th d, all mice treatedwith250mg/kgAPAPexhibitedsevere liver injuryafter24h, andhepatotoxicitywas assessed. Results: Our results showed that pretreatment with Rk1 significantly decreased the levels of serum alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor, and interleukin-1b compared with the APAPgroup.Meanwhile, hepatic antioxidants, including superoxide dismutase andglutathione,were elevated compared with the APAP group. In contrast, a significant decrease in levels of the lipid peroxidation product malondialdehyde was observed in the ginsenoside Rk1-treated group compared with the APAP group. These effectswere associatedwith a significant increase of cytochromeP450 E1 and 4-hydroxynonenal levels in liver tissues. Moreover, ginsenoside Rk1 supplementation suppressed activation of apoptotic pathways by increasing Bcl-2 and decreasing Bax protein expression levels, which was shown using western blotting analysis.Histopathological observation also revealed that ginsenoside Rk1 pretreatment significantly reversed APAP-induced necrosis and inflammatory infiltration in liver tissues. Biological indicators of nitrative stress, such as 3-nitrotyrosine, were also inhibited after pretreatment with Rk1 compared with the APAP group. Conclusion: The results clearly suggest that the underlying molecular mechanisms in the hepatoprotection of ginsenoside Rk1 in APAP-induced hepatotoxicity may be due to its antioxidation, antiapoptosis, anti-inflammation, and antinitrative effects.