• Journal of Microbiology
• /
• 제38권4호
• /
• pp.245-249
• /
• 2000

Catabolic pathways for the degradation of various aromatics by Sphingomonas yanoikuyae Bl are intertwined, joining at the level of substituted benzoates, which are further degraded vita ring cleavage reactions. The mutant strain EK497, which was constructed by deleting a large DNA region containing most of the genes for biphenyl, naphthalene, m-xylene, and m-toluate degradation, was unable to grow on all of the aromatics tested except for benzoate as the sole source of carbon and energy.S. yanoikuyae EK497 was found to possess only catechol ortho-ring cleavage activity due to deletion of the genes for the meta-cleavage pathway. Wild-type S. yanoikuyae Bl grown on benzoate has both catechol orthoand meta-cleavage activity. However, m-xylene and m-toluate, which are metabolized through methylbenzoate, and biphenyl, which is metabolized through benzoate, induce only the meta-cleavage pathway, suggesting the presence of a substrate-dependent induction mechanism.

• Nutrition Research and Practice
• /
• 제3권1호
• /
• pp.64-71
• /
• 2009

Amino acids are fundamental nutrients for protein synthesis and cell growth (increase in cell size). Recently, many compelling evidences have shown that the level of amino acids is sensed by extra- or intra-cellular amino acids sensor(s) and regulates protein synthesis/degradation. Mammalian target of rapamycin complex 1 (mTORC1) is placed in a central position in cell growth regulation and dysregulation of mTOR signaling pathway has been implicated in many serious human diseases including cancer, diabetes, and tissue hypertrophy. Although amino acids are the most potent activator of mTORC1, how amino acids activate mTOR signaling pathway is still largely unknown. This is partly because of the diversity of amino acids themselves including structure and metabolism. In this review, current proposed amino acid sensing mechanisms to regulate mTORC1 and the evidences pro/against the proposed models are discussed.

• Fisheries and Aquatic Sciences
• /
• 제22권9호
• /
• pp.19.1-19.10
• /
• 2019

We investigated the insulin-like growth factor 1 (IGF-1)/AKT signaling pathway involved in muscle formation, growth, and movement in the adductor muscle of triploid Pacific oyster, Crassostrea gigas. Large and small triploid oysters (LTs and STs) cultured under identical conditions were screened, and the signaling pathways of individuals with superior growth were compared and analyzed. mRNA and protein expression levels of actin, troponin, tropomyosin, and myosin, proteins important in muscle formation, were higher in LTs compared with STs. Expression levels of IGF-1, IGF binding protein (IGFBP), and IGFBP complex acid-labile subunit were also higher in LTs compared with STs. Phosphorylation of the IGF receptor as well as that of AKT was high in LTs. In addition, the expression of phosphomammalian target of rapamycin and phospho-glycogen synthase kinase $3{\beta}$ was increased and the expression of Forkhead box O3 was decreased in LTs. Therefore, we suggested that the IGF-1/AKT signaling pathway affects the formation, growth, and movement of the adductor muscle in triploid oysters.

• 약학회지
• /
• 제38권5호
• /
• pp.530-543
• /
• 1994

To study the feasibility of transmucosal delivery of leucine enkephalin (Leu-Enk) and $[D-ala^2]$-leucine enkephalinamide (YAGFL), their degradation extents and pathways in various rabbit mucosa extracts were investigated by high performance liquid chromatography. The degradation of Leu-Enk and YAGFL was observed to follow the first-order kinetics. The degradation half-lives of Leu-Enk in the nasal, rectal and vaginal mucosal extracts were 1.62, 0.37 and 1.12 hrs and those of YAGFL were 30.55, 9.70 and 6.82 hrs, respectively, indicating Leu-Enk was degraded in a more extensive and rapid manner than YAGFL. But the mucosal and serosal extracts of the same mucosa showed the similar degradation rates for both pentapeptides. The degradation was most rapid in the neutral pH and increasing concentrations of substrates retarded the degradation rates. The maior hydrolytic fragments of Leu-Enk were Des-Tyr-Leu-Enk and tyrosine, indicating the enzymatic hydrolysis by aminopeptidases. However, the data also suggested endopeptidases such as dipeptidyl carboxypeptidase and dipeptidyl aminopeptidase could play some role in the degradation of Leu-Enk. On the other hand, the hydrolytic fragments of YAGFL in all the mucosa extracts were mainly Tyr-D-Ala-Gly and Phe-Leu-Amide, demonstrating the hydrolytic breakdown by endopeptidases. The degradation pathways were further explored by concomitantly determining the formation of smaller metabolites of primary hydrolytic fragments of Leu-Enk and YAGFL in the mucosa extracts.

• Molecules and Cells
• /
• 제37권9호
• /
• pp.672-684
• /
• 2014

The exact causes of cell death in Parkinson's disease (PD) remain unknown despite extensive studies on PD.The identification of signaling and metabolic pathways involved in PD might provide insight into the molecular mechanisms underlying PD. The neurotoxin 1-methyl-4-phenylpyridinium ($MPP^+$) induces cellular changes characteristic of PD, and $MPP^+$-based models have been extensively used for PD studies. In this study, pathways that were significantly perturbed in $MPP^+$-treated human neuroblastoma SH-EP cells were identified from genome-wide gene expression data for five time points (1.5, 3, 9, 12, and 24 h) after treatment. The mitogen-activated protein kinase (MAPK) signaling pathway and endoplasmic reticulum (ER) protein processing pathway showed significant perturbation at all time points. Perturbation of each of these pathways resulted in the common outcome of upregulation of DNA-damage-inducible transcript 3 (DDIT3). Genes involved in ER protein processing pathway included ubiquitin ligase complex genes and ER-associated degradation (ERAD)-related genes. Additionally, overexpression of DDIT3 might induce oxidative stress via glutathione depletion as a result of overexpression of CHAC1. This study suggests that upregulation of DDIT3 caused by perturbation of the MAPK signaling pathway and ER protein processing pathway might play a key role in $MPP^+$-induced neuronal cell death. Moreover, the toxicity signal of $MPP^+$ resulting from mitochondrial dysfunction through inhibition of complex I of the electron transport chain might feed back to the mitochondria via ER stress. This positive feedback could contribute to amplification of the death signal induced by $MPP^+$.

• 환경생물
• /
• 제40권3호
• /
• pp.255-266
• /
• 2022

갑각류에서 탈피는 ecdysteroid와 juvenile hormone (JH) 신호 경로에 관여하는 유전자의 상호작용에 의해 조절된다. Ecdysteroid와 달리, 탈피 과정에서 JH 신호 경로 유전자의 역할은 부유성 갑각류에서는 잘 알려져 있지 않다. 본 연구는 기수산 물벼룩(Diaphanosoma celebensis)의 JH 신호경로에서 JH 합성, 수용체, 분해 등에 관여하는 3종의 유전자(JHAMT, Met, JHEH)의 염기서열 분석과 계통 분석을 실시하였다. 또한 탈피 주기에서 이들 유전자의 mRNA 발현양상을 분석하였다. D. celebensis의 JH 관련 유전자는 잘 보존된 domain을 가지고 있었으며, 아미노산 서열 분석과 계통 분석 결과는 이들 단백질이 곤충 및 다른 갑각류의 해당 단백질과 기능적으로 유사한 특징을 나타낸다. 또한 탈피 주기에 따른 유충 호르몬( JH) 신호전달경로 관련 유전자의 발현변화 결과를 통해 이들 유전자가 JH의 합성 및 분해에 관여함으로써 D. celebensis에서 성공적인 탈피에 기여할 것임을 제시하였다. 본 연구는 지각류에서 탈피 주기에서 JH 경로 유전자의 역할을 이해하는 데 도움이 될 것이다.

• BMB Reports
• /
• 제42권9호
• /
• pp.552-560
• /
• 2009

Cyclooxygenases (COX-1 and COX-2) are ER-resident proteins that catalyze the committed step in prostanoid synthesis. COX-1 is constitutively expressed in many mammalian cells, whereas COX-2 is usually expressed inducibly and transiently. Abnormal expression of COX-2 has been implicated in the pathogenesis of chronic inflammation and various cancers; therefore, it is subject to tight and complex regulation. Differences in regulation of the COX enzymes at the posttranscriptional and posttranslational levels also contribute significantly to their distinct patterns of expression. Rapid degradation of COX-2 mRNA has been attributed to AU-rich elements (AREs) at its 3’UTR. Recently, microRNAs that can selectively repress COX-2 protein synthesis have been identified. The mature forms of these COX proteins are very similar in structure except that COX-2 has a unique 19-amino acid (19-aa) segment located near the C-terminus. This C-terminal 19-aa cassette plays an important role in mediation of the entry of COX-2 into the ER-associated degradation (ERAD) system, which transports ER proteins to the cytoplasm for degradation by the 26S proteasome. A second pathway for COX-2 protein degradation is initiated after the enzyme undergoes suicide inactivation following cyclooxygenase catalysis. Here, we discuss these molecular determinants of COX-2 expression in detail.

• Journal of Microbiology and Biotechnology
• /
• 제19권4호
• /
• pp.409-415
• /
• 2009

Galactomyces geotrichum MTCC 1360 degraded the Scarlet RR(100 mg/l) dye within 18 h, under shaking conditions(150 rpm) in malt yeast medium. The optimum pH and the temperature for decolorization were pH 12 and $50^{\circ}C$, respectively. Enzymatic studies revealed an induction of the enzymes, including flavin reductase during the initial stage and lignin peroxidase after complete decolorization of the dye. Decolorization of the dye was induced by the addition of $CaCO_3$ to the medium. EDTA had an inhibitory effect on the dye decolorization along with the laccase activity. The metabolites formed after complete decolorization were analyzed by UV-VIS, HPLC, and FTIR. The GC/MS identification of 3 H quinazolin-4-one, 2-ethylamino-acetamide, 1-chloro-4-nitro-benzene, N-(4-chloro-phenyl)-hydroxylamine, and 4-chloro-pheny-lamine as the final metabolites corroborated with the degradation of Scarlet RR. The phytotoxicity study revealed the nontoxic nature of the final metabolites. A possible degradation pathway is suggested to understand the mechanism used by G. geotrichum and thereby aiding development of technologies for the application of this organism to the cleaning-up of aquatic and terrestrial environments.

• Molecules and Cells
• /
• 제22권3호
• /
• pp.353-359
• /
• 2006

The bone morphogenetic protein (BMP) family has been implicated in control of cartilage development. Here, we demonstrate that BMP-2 promotes chondrogenesis by activating p38 mitogen-activated protein kinase (MAPK), which in turn downregulates $Wnt-7a/{\beta}$-catenin signaling responsible for proteasomal degradation of Sox9. Exposure of mesenchymal cells to BMP-2 resulted in upregulation of Sox9 protein and a concomitant decrease in the level of ${\beta}$-catenin protein and Wnt-7a signaling. In agreement with this, the interaction of Sox9 with ${\beta}$-catenin was inhibited in the presence of BMP-2. Inhibition of the p38 MAPK pathway using a dominant negative mutant led to sustained Wnt-7a signaling and decreased Sox9 expression, with consequent inhibition of precartilage condensation and chondrogenic differentiation. Moreover, overexpression of ${\beta}$-catenin caused degradation of Sox9 via the ubiquitin/26S proteasome pathway. Our results collectively indicate that the increase in Sox9 protein resulting from downregulation of ${\beta}$-catenin/Wnt-7a signaling is mediated by p38 MAPK during BMP-2 induced chondrogenesis in chick wing bud mesenchymal cells.

• Molecules and Cells
• /
• 제47권1호
• /
• pp.100001.1-100001.8
• /
• 2024

In eukaryotes, a primary protein quality control (PQC) process involves the destruction of conformationally misfolded proteins through the ubiquitin-proteasome system. Because approximately one-third of eukaryotic proteomes fold and assemble within the endoplasmic reticulum (ER) before being sent to their destinations, the ER plays a crucial role in PQC. The specific functions and biochemical roles of several E3 ubiquitin ligases involved in ER-associated degradation in mammals, on the other hand, are mainly unknown. We identified 2 E3 ligases, ubiquitin protein ligase E3 component N-recognin 1 (UBR1) and ubiquitin protein ligase E3 component N-recognin 2 (UBR2), which are the key N-recognins in the N-degron pathway and participate in the ER stress response in mammalian cells by modulating their stability. Cells lacking UBR1 and UBR2 are hypersensitive to ER stress-induced apoptosis. Under normal circumstances, these proteins are polyubiquitinated through Lys48-specific linkages and are then degraded by the 26S proteasome. In contrast, when cells are subjected to ER stress, UBR1 and UBR2 exhibit greater stability, potentially as a cellular adaptive response to stressful conditions. Although the precise mechanisms underlying these findings require further investigation, our findings show that cytoplasmic UBR1 and UBR2 have anti-ER stress activities and contribute to global PQC in mammals. These data also reveal an additional level of complexity within the mammalian ER-associated degradation system, implicating potential involvement of the N-degron pathway.