MyMedR

Displaying all 7 publications

Abstract:

Sort:

Fulltext Fluorinated curcumin derivative (Shiga-Y6) modulates the level of thioredoxin-interacting protein (TXNIP) in a mouse model of diabetes

Aldoghachi AF, Yanagisawa D, Pahrudin Arrozi A, Abu Bakar ZH, Taguchi H, Ishigaki S, et al.

Biochem Biophys Res Commun, 2024 Jan 29;694:149392.
PMID: 38142581 DOI: 10.1016/j.bbrc.2023.149392

Thioredoxin interacting protein (TXNIP) has emerged as a significant regulator of β-cell mass and loss, rendering it an attractive target for treating diabetes. We previously showed that Shiga-Y6, a fluorinated curcumin derivative, inhibited TXNIP mRNA and protein expression in vitro, raising the question of whether the same effect could be translated in vivo. Herein, we examined the effect of Shiga-Y6 on TNXIP levels and explored its therapeutic potential in a mouse model of diabetes, Akita mice. We intraperitoneally injected Shiga-Y6 (SY6; 30 mg/kg of body weight) or vehicle into 8-week-old Akita mice for 28 consecutive days. On day 29, the mice were euthanized, following which the serum levels of glucose, insulin, and glucagon were measured using ELISA, the expression of TXNIP in pancreatic tissue lysates was determined using western blotting, and the level of β-cell apoptosis was assessed using the TUNEL assay. TXNIP levels in the pancreatic tissue of Akita mice were significantly elevated compared with wild-type (WT) mice. Shiga-Y6 administration for 28 days significantly lowered those levels compared with Akita mice that received vehicle to a level comparable to WT mice. In immunohistochemical analysis, both α- to β-cell ratio and the number of apoptotic β-cells were significantly reduced in SY6-treated Akita mice, compared with vehicle-treated Akita mice. Findings from the present study suggest a potential of Shiga-Y6 as an antidiabetic agent through lowering TXNIP protein levels and ameliorating pancreatic β-cells apoptosis.

Matched MeSH terms: Thioredoxins/genetics; Thioredoxins/metabolism
NETASA: neural network based prediction of solvent accessibility

Ahmad S, Gromiha MM

Bioinformatics, 2002 Jun;18(6):819-24.
PMID: 12075017

MOTIVATION: Prediction of the tertiary structure of a protein from its amino acid sequence is one of the most important problems in molecular biology. The successful prediction of solvent accessibility will be very helpful to achieve this goal. In the present work, we have implemented a server, NETASA for predicting solvent accessibility of amino acids using our newly optimized neural network algorithm. Several new features in the neural network architecture and training method have been introduced, and the network learns faster to provide accuracy values, which are comparable or better than other methods of ASA prediction.
RESULTS: Prediction in two and three state classification systems with several thresholds are provided. Our prediction method achieved the accuracy level upto 90% for training and 88% for test data sets. Three state prediction results provide a maximum 65% accuracy for training and 63% for the test data. Applicability of neural networks for ASA prediction has been confirmed with a larger data set and wider range of state thresholds. Salient differences between a linear and exponential network for ASA prediction have been analysed.
AVAILABILITY: Online predictions are freely available at: http://www.netasa.org. Linux ix86 binaries of the program written for this work may be obtained by email from the corresponding author.

Matched MeSH terms: Thioredoxins/genetics; Thioredoxins/chemistry
Fulltext Proteomic analysis of whole human saliva detects enhanced expression of interleukin-1 receptor antagonist, thioredoxin and lipocalin-1 in cigarette smokers compared to non-smokers

Jessie K, Pang WW, Haji Z, Rahim A, Hashim OH

Int J Mol Sci, 2010 Nov 09;11(11):4488-505.
PMID: 21151451 DOI: 10.3390/ijms11114488

A gel-based proteomics approach was used to screen for proteins of differential abundance between the saliva of smokers and those who had never smoked. Subjecting precipitated proteins from whole human saliva of healthy non-smokers to two-dimensional electrophoresis (2-DE) generated typical profiles comprising more than 50 proteins. While 35 of the proteins were previously established by other researchers, an additional 22 proteins were detected in the 2-DE saliva protein profiles generated in the present study. When the 2-DE profiles were compared to those obtained from subjects considered to be heavy cigarette smokers, three saliva proteins, including interleukin-1 receptor antagonist, thioredoxin and lipocalin-1, showed significant enhanced expression. The distribution patterns of lipocalin-1 isoforms were also different between cigarette smokers and non-smokers. The three saliva proteins have good potential to be used as biomarkers for the adverse effects of smoking and the risk for inflammatory and chronic diseases that are associated with it.

Matched MeSH terms: Thioredoxins/genetics; Thioredoxins/metabolism*
Proteomics Analysis Revealed that Crosstalk between Helicobacter pylori and Streptococcus mitis May Enhance Bacterial Survival and Reduces Carcinogenesis

Khosravi Y, Loke MF, Goh KL, Vadivelu J

Front Microbiol, 2016;7:1462.
PMID: 27695448

Helicobacter pylori is the dominant species of the human gastric microbiota and is present in the stomach of more than half of the human population worldwide. Colonization by H. pylori causes persistent inflammatory response and H. pylori-induced gastritis is the strongest singular risk factor for the development of gastric adenocarcinoma. However, only a small proportion of infected individuals develop malignancy. Besides H. pylori, other microbial species have also been shown to be related to gastritis. We previously reported that interspecies microbial interaction between H. pylori and S. mitis resulted in alteration of their metabolite profiles. In this study, we followed up by analyzing the changing protein profiles of H. pylori and S. mitis by LC/Q-TOF mass spectrometry to understand the different response of the two bacterial species in a multi-species micro-environment. Differentially-expressed proteins in mono- and co-cultures could be mapped into 18 biological pathways. The number of proteins involve in RNA degradation, nucleotide excision repair, mismatch repair, and lipopolysaccharide (LPS) biosynthesis were increased in co-cultured H. pylori. On the other hand, fewer proteins involve in citrate cycle, glycolysis/ gluconeogenesis, aminoacyl-tRNA biosynthesis, translation, metabolism, and cell signaling were detected in co-cultured H. pylori. This is consistent with our previous observation that in the presence of S. mitis, H. pylori was transformed to coccoid. Interestingly, phosphoglycerate kinase (PGK), a major enzyme used in glycolysis, was found in abundance in co-cultured S. mitis and this may have enhanced the survival of S. mitis in the multi-species microenvironment. On the other hand, thioredoxin (TrxA) and other redox-regulating enzymes of H. pylori were less abundant in co-culture possibly suggesting reduced oxidative stress. Oxidative stress plays an important role in tissue damage and carcinogenesis. Using the in vitro co-culture model, this study emphasized the possibility that pathogen-microbiota interaction may have a protective effect against H. pylori-associated carcinogenesis.

Matched MeSH terms: Thioredoxins
Fulltext Roles of Carotenoids in Invertebrate Immunology

Tan K, Zhang H, Lim LS, Ma H, Li S, Zheng H

Front Immunol, 2019;10:3041.
PMID: 32010132 DOI: 10.3389/fimmu.2019.03041

Carotenoids are biologically active pigments that are well-known to enhance the defense and immunity of the vertebrate system. However, in invertebrates, the role of carotenoids in immunity is not clear. Therefore, this study aims to review the scientific evidence for the role of carotenoids in invertebrate immunization. From the analysis of published literatures and recent studies from our laboratory, it is obvious that carotenoids are involved in invertebrate immunity in two ways. On the one hand, carotenoids can act as antioxidant enzymes to remove singlet oxygen, superoxide anion radicals, and hydroxyl radicals, thereby reducing SOD activity and reducing the cost of immunity. In some organisms, carotenoids have been shown to promote SOD activity by up-regulating the expression of the ZnCuSOD gene. Carotenoids, on the other hand, play a role in the expression and regulation of many genes involved in invertebrate immunity, including thioredoxins (TRX), peptidoglycan recognition receptor proteins (PGRPs), ferritins, prophenoloxidase (ProPO), vitellogenin (Vg), toll-like receptor (TLRs), heat shock proteins (HSPs), and CuZnSOD gene. The information in this review is very useful for updating our understanding of the progress of carotenoid research in invertebrate immunology and to help identify topics for future topics.

Matched MeSH terms: Thioredoxins
Fulltext Cytotoxic and radiosensitising effects of a novel thioredoxin reductase inhibitor in breast cancer

Abdullah NA, Inman M, Moody CJ, Storr SJ, Martin SG

Invest New Drugs, 2021 10;39(5):1232-1241.
PMID: 33768386 DOI: 10.1007/s10637-021-01106-5

Radiotherapy is an effective treatment modality for breast cancer but, unfortunately, not all patients respond fully with a significant number experiencing local recurrences. Overexpression of thioredoxin and thioredoxin reductase has been reported to cause multidrug and radiation resistance - their inhibition may therefore improve therapeutic efficacy. Novel indolequinone compounds have been shown, in pancreatic cancer models, to inhibit thioredoxin reductase activity and exhibit potent anticancer activity. The present study evaluates, using in vitro breast cancer models, the efficacy of a novel indolequinone compound (IQ9) as a single agent and in combination with ionising radiation using a variety of endpoint assays including cell proliferation, clonogenic survival, enzyme activity, and western blotting. Three triple-negative breast cancer (MDA-MB-231, MDA-MB-468, and MDA-MB-436) and two luminal (MCF-7 and T47D) breast cancer cell lines were used. Results show that treatment with IQ9 significantly inhibited thioredoxin reductase activity, and inhibited cell growth and colony formation of breast cancer cells with IC50 values in the low micromolar ranges. Enhanced radiosensitivity of triple-negative breast cancer cells was observed, with sensitiser enhancement ratios of 1.20-1.43, but with no evident radiosensitisation of luminal breast cancer cell lines. IQ9 upregulated protein expression of thioredoxin reductase in luminal but not in triple-negative breast cancer cells which may explain the observed differential radiosensitisation. This study provides important evidence of the roles of the thioredoxin system as an exploitable radiobiological target in breast cancer cells and highlights the potential therapeutic value of indolequinones as radiosensitisers.***This study was not part of a clinical trial. Clinical trial registration number: N/A.

Matched MeSH terms: Thioredoxins/drug effects
Thioredoxin-albumin fusion protein prevents copper enhanced zinc-induced neurotoxicity via its antioxidative activity

Tanaka KI, Shimoda M, Chuang VTG, Nishida K, Kawahara M, Ishida T, et al.

Int J Pharm, 2018 Jan 15;535(1-2):140-147.
PMID: 29122608 DOI: 10.1016/j.ijpharm.2017.11.012

Zinc (Zn) is a co-factor for a vast number of enzymes, and functions as a regulator for immune mechanism and protein synthesis. However, excessive Zn release induced in pathological situations such as stroke or transient global ischemia is toxic. Previously, we demonstrated that the interaction of Zn and copper (Cu) is involved in the pathogenesis of Alzheimer's disease and vascular dementia. Furthermore, oxidative stress has been shown to play a significant role in the pathogenesis of various metal ions induced neuronal death. Thioredoxin-Albumin fusion (HSA-Trx) is a derivative of thioredoxin (Trx), an antioxidative protein, with improved plasma retention and stability of Trx. In this study, we examined the effect of HSA-Trx on Cu2+/Zn2+-induced neurotoxicity. Firstly, HSA-Trx was found to clearly suppress Cu2+/Zn2+-induced neuronal cell death in mouse hypothalamic neuronal cells (GT1-7 cells). Moreover, HSA-Trx markedly suppressed Cu2+/Zn2+-induced ROS production and the expression of oxidative stress related genes, such as heme oxygenase-1. In contrast, HSA-Trx did not affect the intracellular levels of both Cu2+ and Zn2+ after Cu2+/Zn2+ treatment. Finally, HSA-Trx was found to significantly suppress endoplasmic reticulum (ER) stress response induced by Cu2+/Zn2+ treatment in a dose dependent manner. These results suggest that HSA-Trx counteracted Cu2+/Zn2+-induced neurotoxicity by suppressing the production of ROS via interfering the related gene expressions, in addition to the highly possible radical scavenging activity of the fusion protein. Based on these findings, HSA-Trx has great potential as a promising therapeutic agent for the treatment of refractory neurological diseases.

Matched MeSH terms: Thioredoxins