• The Korean Journal of Physiology and Pharmacology
• /
• 제25권2호
• /
• pp.159-166
• /
• 2021

Nicotinamide adenine dinucleotide phosphate oxidases (NOXs) are the major enzymatic source of reactive oxygen species (ROS). NOX2 and NOX4 are expressed in the heart but its role in hypoxia-induced atrial natriuretic peptide (ANP) secretion is unclear. This study investigated the effect of NOX on ANP secretion induced by hypoxia in isolated beating rat atria. The results showed that hypoxia significantly upregulated NOX4 but not NOX2 expression, which was completely abolished by endothelin-1 (ET-1) type A and B receptor antagonists BQ123 (0.3 μM) and BQ788 (0.3 μM). ET-1-upregulated NOX4 expression was also blocked by antagonists of secreted phospholipase A2 (sPLA2; varespladib, 5.0 μM) and cytosolic PLA2 (cPLA2; CAY10650, 120.0 nM), and ET-1-induced cPLA2 expression was inhibited by varespladib under normoxia. Moreover, hypoxia-increased ANP secretion was evidently attenuated by the NOX4 antagonist GLX351322 (35.0 μM) and inhibitor of ROS N-Acetyl-D-cysteine (NAC, 15.0 mM), and hypoxia-increased production of ROS was blocked by GLX351322. In addition, hypoxia markedly upregulated Src expression, which was blocked by ET receptors, NOX4, and ROS antagonists. ET-1-increased Src expression was also inhibited by NAC under normoxia. Furthermore, hypoxia-activated extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (Akt) were completely abolished by Src inhibitor 1 (1.0 μM), and hypoxia-increased GATA4 was inhibited by the ERK1/2 and Akt antagonists PD98059 (10.0 μM) and LY294002 (10.0 μM), respectively. However, hypoxia-induced ANP secretion was substantially inhibited by Src inhibitor. These results indicate that NOX4/Src modulated by ET-1 regulates ANP secretion by activating ERK1/2 and Akt/GATA4 signaling in isolated beating rat hypoxic atria.

• 대한본초학회지
• /
• 제36권2호
• /
• pp.31-42
• /
• 2021

Objectives : This study was undertaken to investigate the hepatoprotective effect of Spatholobi Caulis water extract (SC) to thioacetamide (TAA)-induced acute liver injury (ALI) in rats. Methods : The rats were injected intraperitoneally with TAA (200 mg/kg body weight) and orally administered SC (100 or 200 mg/kg b.w.) daily for 3 days. Liver biomarkers were assessed by serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and ammonia levels. Malondialdehyde (MDA) was measured both serum and liver tissue. In addition, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, anti-oxidant, and inflammation-related proteins were investigated by western blot analysis. Histological examination further confirmed though hematoxylin and eosin stain. Results : The SC treatment reduced liver function markers like GOT and GPT and also remarkably decreased ammonia level. Moreover, the elevated MDA level in TAA-induced group was significantly reduced by SC treatment. NADPH oxidase expression associated with oxidative stress including NOX2, NOX4, and p47phox markedly inhibited by SC administration. SC treatment exerted anti-oxidant effect through the increase of anti-oxidant enzyme including superoxide dismutase (SOD), Catalase, and heme oxygenase-1 (HO-1). The protein expressions of inflammatory cytokines such as tumor necrosis factor-�� (TNF-��), IL-6, and IL-1�� induced by nuclear factor-kappa B (NF-��B) activation were modulated through blocking the phosphorylation of inhibitor of nuclear factor ��B�� (I��B)��. SC treatment also improved histological alterations. Conclusion : These findings suggested that SC administration may be a potential candidate for the prevention or treatment of ALI.

• Journal of Microbiology and Biotechnology
• /
• 제32권3호
• /
• pp.287-293
• /
• 2022

The hydroxylation of methane (CH₄) is crucial to the field of environmental microbiology, owing to the heat capacity of methane, which is much higher than that of carbon dioxide (CO₂). Soluble methane monooxygenase (sMMO), a member of the bacterial multicomponent monooxygenase (BMM) superfamily, is essential for the hydroxylation of specific substrates, including hydroxylase (MMOH), regulatory component (MMOB), and reductase (MMOR). The diiron active site positioned in the MMOH α-subunit is reduced through the interaction of MMOR in the catalytic cycle. The electron transfer pathway, however, is not yet fully understood due to the absence of complex structures with reductases. A type II methanotroph, Methylosinus sporium 5, successfully expressed sMMO and hydroxylase, which were purified for the study of the mechanisms. Studies on the MMOH-MMOB interaction have demonstrated that Tyr76 and Trp78 induce hydrophobic interactions through π-π stacking. Structural analysis and sequencing of the ferredoxin domain in MMOR (MMOR-Fd) suggested that Tyr93 and Tyr95 could be key residues for electron transfer. Mutational studies of these residues have shown that the concentrations of flavin adenine dinucleotide (FAD) and iron ions are changed. The measurements of dissociation constants (K_ds) between hydroxylase and mutated reductases confirmed that the binding affinities were not significantly changed, although the specific enzyme activities were significantly reduced by MMOR-Y93A. This result shows that Tyr93 could be a crucial residue for the electron transfer route at the interface between hydroxylase and reductase.

• Journal of Ecology and Environment
• /
• 제46권3호
• /
• pp.218-242
• /
• 2022

Background: Promising specific growth regulators are employed in the tissue cultures of various bamboo species. Specific natural hardening mixtures support the acclimatization and adaptation of bamboo under protected cultivation. Results: The growth regulators like 2, 4-Dichlorophenoxyacetic acid (2, 4-D), Naphthaleneacetic Acid (NAA), Thidiazuron (TDZ), 6-Benzylaminopurine (BAP), Kinetin, Gelrite, Benzyl Adenine (BA), Indole Butyric Acid (IBA), Coumarin, Putrescine, Gibberellic acid (GA₃), Indole Acetic Acid (IAA) has been widely used for callus induction, root regeneration and imposing plant regeneration in various species of bamboo such as Bambusa spp. and Dendrocalamus spp. Different combinations of growth regulators and phytohormones have been used for regenerating some of the major bamboo species. Natural hardening materials such as cocopeat, vermicompost, perlite, cow dung, farmyard manure, compost, soil, garden soil, and humus soil have been recommended for the acclimatization and adaptation of bamboo species. Standard combinations of growth regulators and hardening mixtures have imposed tissue culture, acclimatization, and adaptation in major bamboo species. Conclusions: Bamboo contributes to soil fertility improvement and stabilization of the environment. Bamboo species are also involved in managing the biogeochemical cycle and have immense potential for carbon sequestration and human use. This paper aims to review the various growth regulators, natural mixtures, and defined media involved in regenerating major bamboo species through in vitro propagation. In addition, the ecological benefits of safeguarding the environment are also briefly discussed.

• Journal of Plant Biotechnology
• /
• 제49권4호
• /
• pp.331-338
• /
• 2022

Sunflower (Helianthus annuus L.) protoplasts were isolated from seven-day-old etiolated hypocotyls of 10 A line and four-week-old fully expanded young leaves of PI 441983 line in vitro seedlings using an enzymatic method. Purified protoplasts were collected by filtration and floatation in sucrose solution. Semi-solid protoplast culture was performed using the L4 regeneration protocol with various culture media and plating densities to achieve the highest efficiencies for protoplast culture of hypocotyl and mesophyll protoplasts of 10 A and PI 441983 lines, respectively. The concentrations in liquid L'4M medium and different plating densities were evaluated in two types of cytokinins, the adenine-type 6-benzyladenine (BA) and the phenylurea-type thidiazuron (TDZ). The highest colony formation was achieved in both sunflower lines when 0.5 mgL^-1 BA and 0.5 mgL^-1 TDZ were applied with a high plating density (3 × 10⁵ protoplasts mL^-1). These conditions led to 38.45% and 39.40% colony formation for hypocotyl protoplasts of the 10 A line and mesophyll protoplasts of the PI 441983 line, respectively. Moreover, many hypocotyl protoplast-derived colonies developed into micro-calli. In addition, superior development of both sunflower protoplasts was observed with all plating densities when BA was used in combination with TDZ. This finding will be applicable to future sunflower hybrid production via somatic hybridization.

• Molecules and Cells
• /
• 제46권8호
• /
• pp.496-512
• /
• 2023

A fructose-enriched diet is thought to contribute to hepatic injury in developing non-alcoholic steatohepatitis (NASH). However, the cellular mechanism of fructose-induced hepatic damage remains poorly understood. This study aimed to determine whether fructose induces cell death in primary hepatocytes, and if so, to establish the underlying cellular mechanisms. Our results revealed that treatment with high fructose concentrations for 48 h induced mitochondria-mediated apoptotic death in mouse primary hepatocytes (MPHs). Endoplasmic reticulum stress responses were involved in fructose-induced death as the levels of phosho-eIF2α, phospho-C-Jun-N-terminal kinase (JNK), and C/EBP homologous protein (CHOP) increased, and a chemical chaperone tauroursodeoxycholic acid (TUDCA) prevented cell death. The impaired oxidation metabolism of fatty acids was also possibly involved in the fructose-induced toxicity as treatment with an AMP-activated kinase (AMPK) activator and a PPAR-α agonist significantly protected against fructose-induced death, while carnitine palmitoyl transferase I inhibitor exacerbated the toxicity. However, uric acid-mediated toxicity was not involved in fructose-induced death as uric acid was not toxic to MPHs, and the inhibition of xanthine oxidase (a key enzyme in uric acid synthesis) did not affect cell death. On the other hand, treatment with inhibitors of the nicotinamide adenine dinucleotide (NAD)⁺-consuming enzyme CD38 or CD38 gene knockdown significantly protected against fructose-induced toxicity in MPHs, and fructose treatment increased CD38 levels. These data suggest that CD38 upregulation plays a role in hepatic injury in the fructose-enriched diet-mediated NASH. Thus, CD38 inhibition may be a promising therapeutic strategy to prevent fructose-enriched diet-mediated NASH.

• Molecules and Cells
• /
• 제46권6호
• /
• pp.351-359
• /
• 2023

Deamination of adenine or cytosine in RNA, called RNA editing, is a constitutively active and common modification. The primary role of RNA editing is tagging RNA right after its synthesis so that the endogenous RNA is recognized as self and distinguished from exogenous RNA, such as viral RNA. In addition to this primary function, the direct or indirect effects on gene expression can be utilized in cancer where a high level of RNA editing activity persists. This report identified actin-related protein 2/3 complex inhibitor (ARPIN) as a target of ADAR1 in breast cancer cells. Our comparative RNA sequencing analysis in MCF7 cells revealed that the expression of ARPIN was decreased upon ADAR1 depletion with altered editing on its 3'UTR. However, the expression changes of ARPIN were not dependent on 3'UTR editing but relied on three microRNAs acting on ARPIN. As a result, we found that the migration and invasion of cancer cells were profoundly increased by ADAR1 depletion, and this cellular phenotype was reversed by the exogenous ARPIN expression. Altogether, our data suggest that ADAR1 suppresses breast cancer cell mobility via the upregulation of ARPIN.

• 한국축산식품학회지
• /
• 제43권6호
• /
• pp.1111-1127
• /
• 2023

Health-promoting preparations of inanimate microorganisms or their components are postbiotics. Since probiotics are sensitive to heat and oxygen, postbiotics are stable during industrial processing and storage. Postbiotics boost poultry growth, feed efficiency, intestinal pathogen reduction, and health, making them acceptable drivers of sustainable poultry production. It contains many important biological properties, such as immunomodulatory, antioxidant, and anti-inflammatory responses. Postbiotics revealed promising antioxidant effects due to higher concentrations of uronic acid and due to some enzyme's production of antioxidants, e.g., superoxide dismutase, glutathione peroxidase, and nicotinamide adenine dinucleotide oxidases and peroxidases. Postbiotics improve intestinal villi, increase lactic acid production, and reduce Enterobacteriaceae and fecal pH, all of which lead to a better immune reaction and health of the gut, as well as better growth performance. P13K/AKT as a potential target pathway for postbiotics-improved intestinal barrier functions. Similarly, postbiotics reduce yolk and plasma cholesterol levels in layers and improve egg quality. It was revealed that favorable outcomes were obtained with various inclusion levels at 1 kg and 0.5 kg. According to several studies, postbiotic compounds significantly increased poultry performance. This review article presents the most recent research investigating the beneficial results of postbiotics in poultry.

• 한국군사과학기술학회지
• /
• 제27권2호
• /
• pp.304-310
• /
• 2024

Ricin is a highly toxic protein which is produced in the seeds of the castor oil plant. Ricin toxin A chain has ribosomal RNA N-glycosylase activity that irreversibly hydrolyses the N-glycosidic bond of the adenine residue at position 4324 within the 28S rRNA. In this study, we developed non-toxic recombinant ricin vaccine(R51) in E. coli expression system, and evaluated efficacy of the R51 according to adjuvants. When the R51 was administered using aluminum hydroxide as an adjuvant, the vaccine efficacy was higher than that of TLR agonists or aluminum phosphate. Because it is time-consuming to administer the vaccine three times at three-week intervals, we investigated the survival rate and antibody titer of mice according to the change of time interval of vaccination. Interestingly, there was no difference in survival rate and antibody titer when R51 was administered at 0, 1, and 3 weeks or 0, 2, and 4 weeks compared to when administered at 0, 3, and 6 weeks. Therefore, the developed R51 vaccine is promising to protect soldiers from Ricin attack.

• Clinical and Experimental Pediatrics
• /
• 제48권7호
• /
• pp.766-771
• /
• 2005

목 적 : 류코트리엔 수용체 길항제는 천식의 병리 반응에 관여하는 cysteiny leukotriene의 생성과 작용을 억제하여 급성기 천식 증상의 치료와 천식 증상의 조절 요법에 사용할 수 있다. 본 연구에서는 소아 천식환자에서 cysteinyl leukotriene 생성에 관여하는 $LTC_4S$ 유전자 다형태와 류코트리엔 수용체 길항제인 montelukast의 임상적 효과를 조사하여 약물유전학적 연관성 유무를 알고자 하였다. 방 법 : 환자군은 경증 지속성 천식과 중등증 지속성 천식환자 161명을 대상으로 하였고, montelukast 5 mg을 하루에 한 번씩 총 8주 동안 투여하였다. $LTC_4S$ 유전자 다형태는 restriction fragment length polymorphism을 이용하여 조사하였다. 결 과 : 대조군에서 LTC4S 유전자형의 분포는 A/A, A/C, C/C가 각각 74.0%, 22.6%, 3.4%였고, 환자군에서는 A/A, A/C, C/C가 각각 70.8%, 23.6%, 5.6%였다. 두 군의 유전자형 분포는 통계적으로 유의한 차이를 보이지 않았고, $LTC_4S$ 유전자형 분포와 천식의 중증도 사이에도 유의한 차이가 없었다. 반응군에서는 경증 지속성 천식환자가 반응이 없는 군에서는 중등증 지속성 천식환자가 더 많았다. 전체 소아 천식환자군에서는 montelukast에 대한 반응군과 반응이 없는 군 사이에 $LTC_4S$ 유전자형에 따른 차이는 없었다. 경증 지속성 천식환자의 반응군에서 adenine 대립유전자를 가진 환자가 많았으나, 중등증 지속성 천식환자에서는 유전자형에 따른 반응군과 반응이 없는 군의 유의한 차이가 없었다. 결 론 : 본 연구에서 소아 경증 지속성 천식환자의 경우에는 통계적으로 adenine 대립유전자가 montelukast에 대한 임상적 효과를 예측할 수 있는 인자라고 할 수 있으나 전체 소아 천식환자에서는 $LTC_4S$ 유전자 다형태와 montelukast의 임상적 효과와의 연관성은 통계적으로 없었다.