Search results for: thioredoxin

Authors: Sunil Mittal, Sukhpreet Singh, Hardeep Kaur

Abstract:

The affinity of thiol group with heavy metals is a well-established phenomenon. The present investigation has been focused on electrochemical response of cysteine and thioredoxin against arsenite (As III) on indium tin oxide (ITO) electrodes. It was observed that both the compounds produce distinct response in free and immobilised form at the electrode. The SEM, FTIR, and impedance studies of the modified electrode were conducted for characterization. Various parameters were optimized to achieve As (III) effect on the reduction potential of the compounds. Cyclic voltammetry and linear sweep voltammetry were employed as the analysis techniques. The optimum response was observed at neutral pH in both the cases, at optimum concentration of 2 mM and 4.27 µM for cysteine and thioredoxin respectively. It was observed that presence of As (III) increases the reduction current of both the moieties. The linear range of detection for As (III) with cysteine was from 1 to 10 mg L⁻¹ with detection limit of 0.8 mg L⁻¹. The thioredoxin was found more sensitive to As (III) and displayed a linear range from 0.1 to 1 mg L⁻¹ with detection limit of 10 µg L⁻¹.

Keywords: arsenite, cyclic voltammetry, cysteine, thioredoxin

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Authors: Narin Salehiyan

Abstract:

The three iodothyronine selenodeiodinases catalyze the start and end of thyroid hormone impacts in vertebrates. Auxiliary examinations of these proteins have been prevented by their indispensably film nature and the wasteful eukaryotic-specific pathway for selenoprotein blend. Hydrophobic cluster examination utilized in combination with Position-specific Iterated Impact uncovers that their extramembrane parcel has a place to the thioredoxin-fold superfamily for which test structure data exists. Besides, a expansive deiodinase locale imbedded within the thioredoxin overlay offers solid similitudes with the dynamic location of iduronidase, a part of the clan GH-A-fold of glycoside hydrolases. This show can clarify a number of comes about from past mutagenesis examinations and grants unused irrefutable experiences into the auxiliary and utilitarian properties of these proteins.

Keywords: glycoside, hydrolase, GH-A-like structure, catalyze

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Authors: Chao Wu

Abstract:

Thioredoxin reductase 2 is a mitochondrial enzyme that belongs to the cellular defense against oxidative stress. We deleted mitochondrial Txnrd2 in a KrasG12D-driven pancreatic tumor model. Despite an initial increase in precursor lesions, tumor incidence decreased significantly. We isolated cancer cell lines from these genetically engineered mice and observed an impaired proliferation and colony formation. Reactive Oxygen Species, as determined by DCF fluorescence, were increased. We detected a higher mitochondrial copy number in Txnrd2-deficient cells (KTP). However, measurement of mitochondrial bioenergetics showed no impairment of mitochondrial function and comparable O₂-consumption and extracellular acidification rates. In addition, the mitochondrial complex composition was affected in Txnrd2 deleted cell lines. To gain better insight into the role of Txnrd2, we deleted Txnrd2 in clones from parental KrasG12D cell lines using Crispr/Cas9 technology. The deletion was confirmed by western blot and activity assay. Interestingly, and in line with previous RNA expression analysis, we saw changes in EMT markers in Txnrd2 deleted cell lines and control cell lines. This might help us explain the reduced tumor incidence in KrasG12D; Txnrd2∆panc mice.

Keywords: PDAC, TXNRD2, epithelial-to-mesenchymal-transition, ROS

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Authors: Zi-Han Li, Lu Fang, Liang Wu, Dong-Yuan Chang, Manyuan Dong, Liang Ji, Qi Zhang, Ming-Hui Zhao, Sydney C. W. Tang, Lemin Zheng, Min Chen

Abstract:

Uncoupling of mitochondrial respiration by chemical uncouplers has proven effective in ameliorating obesity, insulin resistance, and hyperglycemia, which were risk factors for diabetic nephropathy (DN). Recently, we found that ANXA1 could improve mitochondrial function to mitigate DN progression. However, the underlying mechanism is not fully clear yet. Here, we identified uncoupling protein 1 (UCP1), an inner membrane protein of mitochondria, as a key to mitochondrial homeostasis improved by ANXA1. Specifically, ANXA1 attenuated mitochondrial dysfunction via appropriately upregulating UCP1 by stabilizing its transcription factor GATA binding protein 3 (GATA3) by combining it with thioredoxin. Moreover, specific overexpression of UCP1 in the renal cortex rescued renal injuries in diabetic Anxa1-KO mice. UCP1 deletion aggravated renal injuries in HFD/STZ-induced diabetic mice. Mechanistically, UCP1 reduced mitochondrial fission through the aristaless-related homeobox (ARX)/cardiolipin synthase 1 (CRLS1) pathway. Therapeutically, CL316243, a UCP1 agonist, could attenuate established DN in db/db mice. This work established an alternative principle to harness the power of uncouplers for the treatment of DN.

Keywords: diabetic nephropathy, uncoupling protein 1, mitochondrial homeostasis, cardiolipin metabolism

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Authors: Zi-Han Li, Lu Fang, Liang Wu, Dong-Yuan Chang, Manyuan Dong, Liang Ji, Qi Zhang, Ming-Hui Zhao, Sydney C.W. Tang, Lemin Zheng, Min Chen

Abstract:

Uncoupling of mitochondrial respiration by chemical uncouplers has proven effective in ameliorating obesity, insulin resistance, and hyperglycemia, which were risk factors for diabetic nephropathy (DN). Recently, it was found that annexin A1(ANXA1) could improve mitochondrial function to mitigate DN progression. However, the underlying mechanism is not fully clear yet. Here, it was identified that uncoupling protein 1 (UCP1), an inner membrane protein of mitochondria, as a key to mitochondrial homeostasis improved by ANXA1. Specifically, ANXA1 attenuated mitochondrial dysfunction via appropriately upregulating UCP1 by stabilizing its transcription factor GATA binding protein 3 (GATA3) through combining with thioredoxin. Moreover, specific overexpression of UCP1 in renal cortex rescued renal injuries in diabetic Anxa1-KO mice. UCP1 deletion aggravated renal injuries in HFD/STZ-induced diabetic mice. Mechanistically, UCP1 reduced mitochondrial fission through the aristaless-related homeobox (ARX)/cardiolipin synthase 1 (CRLS1) pathway. Therapeutically, CL316243, a UCP1 agonist, could attenuate established DN in db/db mice. This work established a novel principle to harness the power of uncouplers for the treatment of DN.

Keywords: diabetic nephropathy, uncoupling protein 1, mitochondrial homeostasis, cardiolipin metabolism

Procedia PDF Downloads 78