• Title/Summary/Keyword: molecular mechanism

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Distinctive contribution of two additional residues in protein aggregation of Aβ42 and Aβ40 isoforms

  • Dongjoon Im;Tae Su Choi
    • BMB Reports
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    • v.57 no.6
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    • pp.263-272
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    • 2024
  • Amyloid-β (Aβ) is one of the amyloidogenic intrinsically disordered proteins (IDPs) that self-assemble to protein aggregates, incurring cell malfunction and cytotoxicity. While Aβ has been known to regulate multiple physiological functions, such as enhancing synaptic functions, aiding in the recovery of the blood-brain barrier/brain injury, and exhibiting tumor suppression/antimicrobial activities, the hydrophobicity of the primary structure promotes pathological aggregations that are closely associated with the onset of Alzheimer's disease (AD). Aβ proteins consist of multiple isoforms with 37-43 amino acid residues that are produced by the cleavage of amyloid-β precursor protein (APP). The hydrolytic products of APP are secreted to the extracellular regions of neuronal cells. Aβ 1-42 (Aβ42) and Aβ 1-40 (Aβ40) are dominant isoforms whose significance in AD pathogenesis has been highlighted in numerous studies to understand the molecular mechanism and develop AD diagnosis and therapeutic strategies. In this review, we focus on the differences between Aβ42 and Aβ40 in the molecular mechanism of amyloid aggregations mediated by the two additional residues (Ile41 and Ala42) of Aβ42. The current comprehension of Aβ42 and Aβ40 in AD progression is outlined, together with the structural features of Aβ42/Aβ40 amyloid fibrils, and the aggregation mechanisms of Aβ42/Aβ40. Furthermore, the impact of the heterogeneous distribution of Aβ isoforms during amyloid aggregations is discussed in the system mimicking the coexistence of Aβ42 and Aβ40 in human cerebrospinal fluid (CSF) and plasma.

Similarity of Gene Expression Profiles in Primary Brain Tumors with the Toxic Mechanism by Environmental Contaminants

  • Kim, Yu-Ri;Kim, Ki-Nam;Park, Yoon-Hee;Ryu, Yeon-Mi;Sohn, Sung-Hwa;Seo, Sang-Hui;Lee, Seung-Ho;Kim, Hye-Won;Lee, Kweon-Haeng;Kim, Meyoung-Kon
    • Molecular & Cellular Toxicology
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    • v.1 no.3
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    • pp.209-215
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    • 2005
  • Recently, a large number of clinical experiments have shown that exposure of organic pollutants lead to various cancers through the abnormal cell growth. Environmental pollutants, such as 2, 3, 7, 8-Tetrachloro dibenzo-p-dioxin (TCDD) and polycyclic aromatic hydrocarbons (PAHs), are carcinogen and are known to cause the cognitive disability and motor dysfunction in the developing of brain. The effects of these pollutants on neurodevelopmental disorder is well established, but the underlying mechanism(s) and similarity of gene expression profiles in human brain tumors with organic pollutants still remain unclear. In this study, we first examined the gene expression profiles in glioblastomas compared with meningioma that are kinds of primary human brain tumor by using human cDNA microarray. The results of cDNA microarray analysis revealed that 26 genes were upregulated (Z-ratio>2.0) and 14 genes were downregulated (Z-ratio<-2.0) in glioblastoma compared with meningioma. From the altered gene patterns, mitogen-activated protein kinase (MAPK) signaling related genes, such as MAP2K3, MAP3K11 and jun activated domain binding protein, and transcription factors, such as UTF2 and TF12, were upregulated in glioblastoma. Also, we tried to investigate the relation between important genes up- and down-regulated in giloblastoma and various organic pollutants. Therefore, the identification of changes in the patterns of gene expression may provide a better understanding of the molecular mechanisms involved in human primary brain tumors and of the relation between gene expression profiles and organic pollutants in brain tissue.

Effects of Sodium Fluoride on the Water Transport in Leaves of Barley and Rice under Salt Stress in the Light

  • Hwang, Hong-Jin;Oh, Kwang-Hoon;Park, Phun-Bum;Lee, Choon-Hwan
    • Journal of Photoscience
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    • v.11 no.1
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    • pp.25-28
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    • 2004
  • The kinetics of the loss of leaf fresh weight during incubation of barley and rice leaves in 9% or 15% NaCl solutions were biphasic, indicating the existence of a controlling mechanism for water transport. The first rapid phases reached their plateaus within 1 and 2 h in the case of rice and barley leaves, respectively. When barley leaves were fed with sodium fluoride, an inhibitor of phosphatase inhibitor, through their epicotyls for 3 h in darkness, prior to the treatment of NaCl, the biphasic pattern shown during NaCl treatment was disappeared resulting in linear decreases in the relative fresh weights. The results suggest that NaF accelerates salt-induced water efflux from plant cells, possibly by inhibiting the protection mechanism that may act in NaF-untreated leaves. The linear water loss can be explained in terms of phosphorylation of aquaporin by blocking its dephosphorylation in the presence of the phosphatase inhibitor to keep aquaporin in a phosphorylated form. However, the effect of NaF shown in barley leaves were not observed in rice. These results suggest that the regulation of water transport depends on plant species, and the mechanism for the controlling water transport in rice is different from that of barley.

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A systematic mRNA control mechanism for germline stem cell homeostasis and cell fate specification

  • Lee, Myon-Hee;Mamillapalli, Srivalli Swathi;Keiper, Brett D.;Cha, Dong Seok
    • BMB Reports
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    • v.49 no.2
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    • pp.93-98
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    • 2016
  • Germline stem cells (GSCs) are the best understood adult stem cell types in the nematode Caenorhabditis elegans, and have provided an important model system for studying stem cells and their cell fate in vivo, in mammals. In this review, we propose a mechanism that controls GSCs and their cell fate through selective activation, repression and mobilization of the specific mRNAs. This mechanism is acutely controlled by known signal transduction pathways (e.g., Notch signaling and Ras-ERK MAPK signaling pathways) and P granule (analogous to mammalian germ granule)-associated mRNA regulators (FBF-1, FBF-2, GLD-1, GLD-2, GLD-3, RNP-8 and IFE-1). Importantly, all regulators are highly conserved in many multi-cellular animals. Therefore, GSCs from a simple animal may provide broad insight into vertebrate stem cells (e.g., hematopoietic stem cells) and their cell fate specification.

Mechanism of Dextran Synthesis by Dextransucrase (Dextransucrase에 의한 Dextran 생성기작에 관한 연구)

  • 윤명희;구윤모
    • KSBB Journal
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    • v.9 no.1
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    • pp.1-7
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    • 1994
  • A qualitative study was made on the mechanism of dextran synthesis by dextransucrase. Enzymatic synthesis of dextran was experimentally studied with initial sucrose concentration from 50g/$\ell$ to 150g/$\ell$. The molecular weight distribution of synthesized dextran was measured by using on-line gel Permeation chromatographic system Sucrose was observed not to work as a primer within the range of concentration tested. At the initial sucrose concentration of 50g/$\ell$, dextran with molecular weight of medium range ($10^4-2{\times}10^6$) was synthesized due to the mass transfer limitation of sucrose. The amount of the dextran of medium range decreased with the initial sucrose concentration. Dextran was likely to be synthesized by radical chain polymerization mechanism since the dextran of medium range was not produced at higher sucrose concentrations.

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Evidence for the association of peroxidases with the antioxidant effect of p-coumaric acid in endothelial cells exposed to high glucose plus arachidonic acid

  • Lee, Seung-Jin;Mun, Gyeong-In;An, Sang-Mi;Boo, Yong-Chool
    • BMB Reports
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    • v.42 no.9
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    • pp.561-567
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    • 2009
  • Although many plant-derived phenolic compounds display antioxidant effects in biological systems, their mechanism of action remains controversial. In this study, the mechanism by which p-coumaric acid (p-CA) performs its antioxidant action was investigated in bovine aortic endothelial cells under oxidative stress due to high levels of glucose (HG) and arachidonic acid (AA), a free fatty acid. p-CA prevented lipid peroxidation and cell death due to HG+AA without affecting the production of reactive oxygen species. The antioxidant effect of p-CA was not decreased by buthionine-(S,R)-sulfoximine, an inhibitor of cellular GSH synthesis. In contrast, pretreatment with p-CA caused the induction of peroxidases that decomposed t-butyl hydroperoxide in a p-CA-dependent manner. Furthermore, the antioxidant effect of p-CA was significantly mitigated by methimazole, which was shown to inhibit the catalytic activity of 'p-CA peroxidases' in vitro. Therefore, it is suggested that the induction of these previously unidentified 'p-CA peroxidases' is responsible for the antioxidant effect of p-CA.