Molecular basis of the redox regulation of SUMO proteases: a protective mechanism of intermolecular disulfide linkage against irreversible sulfhydryl oxidation

2007 ◽  
Vol 22 (1) ◽  
pp. 127-137 ◽  
Author(s):  
Zheng Xu ◽  
Levina Suk Mi Lam ◽  
Lok Hei Lam ◽  
So Fun Chau ◽  
Tzi Bun Ng ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Redox Regulation ◽  
Protective Mechanism ◽  
Disulfide Linkage ◽  
Sumo Proteases ◽  
Sulfhydryl Oxidation

scholarly journals The C. elegans miR-235 regulates the toxicity of graphene oxide via targeting the nuclear hormone receptor DAF-12 in the intestine

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tiantian Guo ◽  
Lu Cheng ◽  
Huimin Zhao ◽  
Yingying Liu ◽  
Yunhan Yang ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Signaling Pathway ◽  
Hormone Receptor ◽  
Molecular Basis ◽  
Mapk Signaling ◽  
Nuclear Hormone Receptor ◽  
In Vivo Model ◽  
Protective Mechanism ◽  
C Elegans

Abstract The increased application of graphene oxide (GO), a new carbon-based engineered nanomaterial, has generated a potential toxicity in humans and the environment. Previous studies have identified some dysregulated microRNAs (miRNAs), such as up-regulated mir-235, in organisms exposed to GO. However, the detailed mechanisms of the dysregulation of miRNA underlying GO toxicity are still largely elusive. In this study, we employed Caenorhabditis elegans as an in vivo model to investigate the biological function and molecular basis of mir-235 in the regulation of GO toxicity. After low concentration GO exposure, mir-235 (n4504) mutant nematodes were sensitive to GO toxicity, implying that mir-235 mediates a protection mechanism against GO toxicity. Tissue-specific assays suggested that mir-235 expressed in intestine is required for suppressing the GO toxicity in C. elegans. daf-12, a gene encoding a member of the steroid hormone receptor superfamily, acts as a target gene of mir-235 in the nematode intestine in response to GO treatment, and RNAi knockdown of daf-12 suppressed the sensitivity of mir-235(n4503) to GO toxicity. Further genetic analysis showed that DAF-12 acted in the upstream of DAF-16 in insulin/IGF-1 signaling pathway and PMK-1 in p38 MAPK signaling pathway in parallel to regulate GO toxicity. Altogether, our results revealed that mir-235 may activate a protective mechanism against GO toxicity by suppressing the DAF-12-DAF-16 and DAF-12-PMK-1 signaling cascade in nematodes, which provides an important molecular basis for the in vivo toxicity of GO at the miRNA level.

scholarly journals Redox Regulation of Large Conductance Ca2+-activated K+ Channels in Smooth Muscle Cells

1997 ◽  
Vol 110 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Zhao-Wen Wang ◽  
Masayuki Nara ◽  
Yong-Xiao Wang ◽  
Michael I. Kotlikoff
Keyword(s):  
Redox Regulation ◽  
Channel Gating ◽  
K Channel ◽  
Dependent Manner ◽  
Channel Activity ◽  
Concentration Dependent Manner ◽  
K Channels ◽  
Sulfhydryl Oxidation ◽  
Excised Patches ◽  
Redox Agents

The effects of sulfhydryl reduction/oxidation on the gating of large-conductance, Ca2+-activated K+ (maxi-K) channels were examined in excised patches from tracheal myocytes. Channel activity was modified by sulfhydryl redox agents applied to the cytosolic surface, but not the extracellular surface, of membrane patches. Sulfhydryl reducing agents dithiothreitol, β-mercaptoethanol, and GSH augmented, whereas sulfhydryl oxidizing agents diamide, thimerosal, and 2,2′-dithiodipyridine inhibited, channel activity in a concentration-dependent manner. Channel stimulation by reduction and inhibition by oxidation persisted following washout of the compounds, but the effects of reduction were reversed by subsequent oxidation, and vice versa. The thiol-specific reagents N-ethylmaleimide and (2-aminoethyl)methanethiosulfonate inhibited channel activity and prevented the effect of subsequent sulfhydryl oxidation. Measurements of macroscopic currents in inside-out patches indicate that reduction only shifted the voltage/nPo relationship without an effect on the maximum conductance of the patch, suggesting that the increase in nPo following reduction did not result from recruitment of more functional channels but rather from changes of channel gating. We conclude that redox modulation of cysteine thiol groups, which probably involves thiol/disulfide exchange, alters maxi-K channel gating, and that this modulation likely affects channel activity under physiological conditions.

scholarly journals Redox Regulation by Protein S-Glutathionylation: From Molecular Mechanisms to Implications in Health and Disease

2020 ◽  
Vol 21 (21) ◽  
pp. 8113 ◽  
Author(s):  
Aysenur Musaogullari ◽  
Yuh-Cherng Chai
Keyword(s):  
Protein Function ◽  
Liver Diseases ◽  
Redox Regulation ◽  
Molecular Mechanisms ◽  
Protein S ◽  
Protective Mechanism ◽  
Post Translational Modification ◽  
Physiological Processes ◽  
Health And Disease ◽  
Mixed Disulfides

S-glutathionylation, the post-translational modification forming mixed disulfides between protein reactive thiols and glutathione, regulates redox-based signaling events in the cell and serves as a protective mechanism against oxidative damage. S-glutathionylation alters protein function, interactions, and localization across physiological processes, and its aberrant function is implicated in various human diseases. In this review, we discuss the current understanding of the molecular mechanisms of S-glutathionylation and describe the changing levels of expression of S-glutathionylation in the context of aging, cancer, cardiovascular, and liver diseases.

scholarly journals Molecular Basis for the Interactions of Human Thioredoxins with Their Respective Reductases

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Md Faruq Hossain ◽  
Yana Bodnar ◽  
Calvin Klein ◽  
Clara Ortegón Salas ◽  
Elias S. J. Arnér ◽  
...  
Keyword(s):  
Electron Transfer ◽  
Active Site ◽  
Molecular Basis ◽  
Redox Regulation ◽  
Transfer Reaction ◽  
Catalytic Efficiency ◽  
Electron Transfer Reaction ◽  
Wild Type ◽  
Electrostatic Properties ◽  
Encounter Complex

The mammalian cytosolic thioredoxin (Trx) system consists of Trx1 and its reductase, the NADPH-dependent seleno-enzyme TrxR1. These proteins function as electron donor for metabolic enzymes, for instance in DNA synthesis, and the redox regulation of numerous processes. In this work, we analysed the interactions between these two proteins. We proposed electrostatic complementarity as major force controlling the formation of encounter complexes between the proteins and thus the efficiency of the subsequent electron transfer reaction. If our hypothesis is valid, formation of the encounter complex should be independent of the redox reaction. In fact, we were able to confirm that also a redox inactive mutant of Trx1 lacking both active site cysteinyl residues (C32,35S) binds to TrxR1 in a similar manner and with similar kinetics as the wild-type protein. We have generated a number of mutants with alterations in electrostatic properties and characterised their interaction with TrxR1 in kinetic assays. For human Trx1 and TrxR1, complementary electrostatic surfaces within the area covered in the encounter complex appear to control the affinity of the reductase for its substrate Trx. Electrostatic compatibility was even observed in areas that do not form direct molecular interactions in the encounter complex, and our results suggest that the electrostatic complementarity in these areas influences the catalytic efficiency of the reduction. The human genome encodes ten cytosolic Trx-like or Trx domain-containing proteins. In agreement with our hypothesis, the proteins that have been characterised as TrxR1 substrates also show the highest similarity in their electrostatic properties.

Molecular Basis for the Redox Regulation of the Src Kinase

2016 ◽  
Vol 100 ◽  
pp. S40
Author(s):  
David E. Heppner ◽  
Christopher M. Dustin ◽  
Chenyi Liao ◽  
Milena Hristova ◽  
Bin Deng ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Redox Regulation ◽  
Src Kinase

SUMO Proteases: Redox Regulation and Biological Consequences

2009 ◽  
Vol 11 (6) ◽  
pp. 1453-1484 ◽  
Author(s):  
Zheng Xu ◽  
Ho Yin Chan ◽  
Wai Ling Lam ◽  
Kwok Ho Lam ◽  
Levina Suk Mi Lam ◽  
...  
Keyword(s):  
Redox Regulation ◽  
Sumo Proteases

Renilla Bioluminescence: A Morphologic Approach to the Location of Photocytes

1974 ◽  
Vol 32 ◽  
pp. 208-209
Author(s):  
Ben O. Spurlock ◽  
Milton J. Cormier
Keyword(s):  
Excited State ◽  
Ground State ◽  
Molecular Basis ◽  
Light Emission ◽  
Chemical Basis ◽  
Electronic Excited State ◽  
Colonial Form ◽  
The Common ◽  
Eighteenth And Nineteenth Centuries ◽  
Catalyzed Oxidation

The phenomenon of bioluminescence has fascinated layman and scientist alike for many centuries. During the eighteenth and nineteenth centuries a number of observations were reported on the physiology of bioluminescence in Renilla, the common sea pansy. More recently biochemists have directed their attention to the molecular basis of luminosity in this colonial form. These studies have centered primarily on defining the chemical basis for bioluminescence and its control. It is now established that bioluminescence in Renilla arises due to the luciferase-catalyzed oxidation of luciferin. This results in the creation of a product (oxyluciferin) in an electronic excited state. The transition of oxyluciferin from its excited state to the ground state leads to light emission.

Androgen-induced plasticity at a “vocal” neuromuscular synapse

1994 ◽  
Vol 52 ◽  
pp. 32-33
Author(s):  
Darcy B. Kelley ◽  
Martha L. Tobias ◽  
Mark Ellisman
Keyword(s):  
Xenopus Laevis ◽  
Motor Neurons ◽  
Sexual Differentiation ◽  
Molecular Basis ◽  
Neuromuscular Synapse ◽  
Sexually Dimorphic ◽  
Intracellular Protein ◽  
Developmental Program ◽  
Androgen Action ◽  
Clawed Frog

Brain and muscle are sexually differentiated tissues in which masculinization is controlled by the secretion of androgens from the testes. Sensitivity to androgen is conferred by the expression of an intracellular protein, the androgen receptor. A central problem of sexual differentiation is thus to understand the cellular and molecular basis of androgen action. We do not understand how hormone occupancy of a receptor translates into an alteration in the developmental program of the target cell. Our studies on sexual differentiation of brain and muscle in Xenopus laevis are designed to explore the molecular basis of androgen induced sexual differentiation by examining how this hormone controls the masculinization of brain and muscle targets.Our approach to this problem has focused on a highly androgen sensitive, sexually dimorphic neuromuscular system: laryngeal muscles and motor neurons of the clawed frog, Xenopus laevis. We have been studying sex differences at a synapse, the laryngeal neuromuscular junction, which mediates sexually dimorphic vocal behavior in Xenopus laevis frogs.

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