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Tingzhang Hu,Zongli Hu,Hua Zeng,Xiaoxiao Qv,Guoping Chen 한국식물생명공학회 2015 Plant biotechnology reports Vol.9 No.1
TomloxD is a lipoxygenase from Lycopersiconesculentum Mill, which has lipoxygenase activity. Theexpression of TomloxD can be stimulated by wounding,pathogen infection, jasmonate, and systemin. To investigatethe function of TomloxD, transgenic tomato plantssilencing tomloxD gene was produced. The suppression ofTomloxD expression led to a marked reduction in the levelsof lipoxygenase activity and endogenous jasmonic acidcontent, which suggested TomloxD can catalyze a-linolenicacids to produce (13S)-hydroperoxyoctadecatrienoicacid (13-HPOT), and the 13-HPOT is metabolized furtherto synthesize jasmonic acid. Real-time RT-PCR revealedthat the expression of defense genes LeHSP90, LePR1 andLePR6 was also less in the transformants than in the wildtypetomato plant. Resistance assay showed that the suppressionof TomloxD in transgenic tomato plants reducedthermotolerance of tomato and increased its susceptibilityto Cladosporium fulvum. Collectively, the data presentedhere suggest that the TomloxD plays a role as a componentof the octadecanoid defense-signaling pathway andinvolved in the generation of endogenous jasmonic acid,and in turn regulates the expression of plant defense genesand resistance to high temperature and pathogen attack.
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Multiple functional self-association interfaces in plant TIR domains
Zhang, Xiaoxiao,Bernoux, Maud,Bentham, Adam R.,Newman, Toby E.,Ve, Thomas,Casey, Lachlan W.,Raaymakers, Tom M.,Hu, Jian,Croll, Tristan I.,Schreiber, Karl J.,Staskawicz, Brian J.,Anderson, Peter A.,Soh National Academy of Sciences 2017 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.114 No.10
<P>The self-association of Toll/interleukin-1 receptor/resistance protein (TIR) domains has been implicated in signaling in plant and animal immunity receptors. Structure-based studies identified different TIR-domain dimerization interfaces required for signaling of the plant nucleotide-binding oligomerization domain-like receptors (NLRs) L6 from flax and disease resistance protein RPS4 from Arabidopsis. Here we show that the crystal structure of the TIR domain from the Arabidopsis NLR suppressor of npr1-1, constitutive 1 (SNC1) contains both an L6-like interface involving helices alpha D and alpha E (DE interface) and an RPS4-like interface involving helices alpha A and alpha E (AE interface). Mutations in either the AE- or DE-interface region disrupt cell-death signaling activity of SNC1, L6, and RPS4 TIR domains and full-length L6 and RPS4. Self-association of L6 and RPS4 TIR domains is affected by mutations in either region, whereas only AE-interface mutations affect SNC1 TIR-domain self-association. We further show two similar interfaces in the crystal structure of the TIR domain from the Arabidopsis NLR recognition of Peronospora parasitica 1 (RPP1). These data demonstrate that both the AE and DE self-association interfaces are simultaneously required for self-association and cell-death signaling in diverse plant NLRs.</P>
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Haijun Qu,Xiaoxiao Hu,Xiaoli Shi,Chuan Wang,Longyuan Wang,Guoping Wang 한국통합생물학회 2019 Animal cells and systems Vol.23 No.3
N-(2-pyridylmethyl)-2-hydroxiymethyl-1-pyrrolidinyl-4-(3-chloro-4-methoxy-benzylamino)-5- pyrimidine-carboxamide (NHPPC) is a new potential of type 5 phosphodiesterase (PDE5) inhibitors, synthesized from the avanafil analogue for the treatment of erectile dysfunction. The targets of this article were to assess plasma protein binding, liver microsomal metabolic stability, inhibition and induction on cytochrome P450 isozymes and the pharmacokinetics of NHPPC. Equilibrium dialysis technique was applied to determine Plasma protein binding (PPB) and NHPPC was evaluated in male Sprague–Dawley rats and Beagle dogs in vivo pharmacokinetic. The NHPPC was highly bound to plasma proteins in rats, dogs and human tested and the mean values for PPB rate were 96.2%, 99.6% and 99.4%, respectively. After in vitro liver microsomes incubated for 60 min, the percent remaining of NHPPC was 42.8%, 0.8% and 42.0% in rats, dogs and human, respectively. In vitro intrinsic clearance was found to be 0.0233, 0.1204 and 0.0214 mL/min/mg protein in rat, dog and human liver microsomes of NHPPC, respectively. NHPPC showed no significant inhibitory effects on major CYP450 enzymes, and had no significant induction potential on CYP1A2 and CYP3A4. Following oral administration in rats and dogs, tmax was 6 and 0.5 h, respectively. The clearance for NHPPC was 1.19 and 1.46 L/h/kg in rats and dogs, respectively. And absolute bioavailability in rat and dog were approximately 34.5% and 53.1%, respectively. These results showed that NHPPC has a good development prospect.
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( Junfeng Lu ),( Xiaoxiao Wang ),( Yunxia Zhu ),( Lina Ma ),( Sujun Zheng ),( Zhongjie Hu ),( Xinyue Chen ) 대한간학회 2021 Gut and Liver Vol.15 No.6
Background/Aims: To investigate postpartum hepatic flares and associated factors in highly vi remic pregnant patients in the immune tolerance phase who adopted telbivudine (LdT) treatment in the last trimester to reduce vertical transmission of hepatitis B virus. Methods: Hepatitis B e antigen (HBeAg)-positive, highly viremic pregnant women were recruited for this prospective study. Treatment with LdT was started from 28 weeks of gestation. Virologi cal and biochemical markers were examined before LdT treatment, antepartum and postpartum. Serial blood samples at the same time were collected to detect cytokines and cortisol (COR). Results: Fifty-six of 153 patients (36.6%) had postpartum hepatic flares, defined as a 2-fold increase in alanine aminotransferase 6 weeks after delivery. Age and the antepartum alanine aminotransferase and postpartum HBeAg levels were independent influencing factors of post partum hepatic flares. Cytokines showed no regularity during or after pregnancy. Compared with the patients with no postpartum flares, the patients with flares had lower baseline interferon γ and COR levels (p=0.022 and p=0.028) and higher postpartum interferon γ levels (p=0.026). Conclusions: A high proportion of highly viremic and immune-tolerant pregnant patients treated with LdT in the last trimester had postpartum hepatic flares, which implied that these patients entered the immune clearance phase after delivery. Thus, this may create an appropriate op portunity for re-antiviral therapy. (Gut Liver 2021;15:887-894)
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