Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox SignalingReviewing Editors:Jerzy Beltowski, Joseph Burgoyne, Gabor Csanyi, Sergey Dikalov, Frank Krause, Anibal Vercesi, and Jeremy Ward DOI
Petr Ježek, Blanka Holendová, Keith Garlid

et al.

Antioxidants and Redox Signaling, Journal Year: 2018, Volume and Issue: 29(7), P. 667 - 714

Published: Jan. 20, 2018

Mitochondria are the energetic, metabolic, redox, and information signaling centers of cell. Substrate pressure, mitochondrial network dynamics, cristae morphology state integrated by protonmotive force Δp or its potential component, ΔΨ, which attenuated proton backflux into matrix, termed uncoupling. The uncoupling proteins (UCP1-5) play an eminent role in regulation each mentioned aspects, being involved numerous physiological events including redox signaling. Recent Advances: UCP2 structure, purine nucleotide fatty acid (FA) binding sites, strongly support FA cycling mechanism: expels anions, whereas is achieved membrane protonated FA. Nascent FAs, cleaved phospholipases, preferential. resulting dissipation decreases superoxide formation dependent on Δp. UCP-mediated antioxidant protection impairment expected to a major cell physiology pathology. Moreover, UCP2-mediated aspartate, oxaloacetate, malate antiport with phosphate alter metabolism cancer cells.A wide range UCP effects participations have been reported; however, mechanisms activation still debated. Switching off/on protonophoretic function might serve as either employing/releasing extra capacity systems directly increasing/decreasing sources. Rapid degradation, levels, elevation nucleotides, decreased Mg2+, increased pyruvate accumulation may initiate signaling.Issues such participation glucose sensing, neuronal (synaptic) function, immune should be elucidated. Antioxid. Redox Signal. 29, 667-714.

Language: Английский

Diabetic cardiomyopathy: Mechanisms and new treatment strategies targeting antioxidant signaling pathways DOI

Karina Huynh,

Bianca C. Bernardo, Julie R. McMullen

et al.

Pharmacology & Therapeutics, Journal Year: 2014, Volume and Issue: 142(3), P. 375 - 415

Published: Jan. 22, 2014

Language: Английский

Citations

513
Hydrogen peroxide – production, fate and role in redox signaling of tumor cells DOI Creative Commons

Claudia Lennicke,

Jette Rahn,

Rudolf Lichtenfels

et al.

Cell Communication and Signaling, Journal Year: 2015, Volume and Issue: 13(1)

Published: Sept. 14, 2015

Hydrogen peroxide (H2O2) is involved in various signal transduction pathways and cell fate decisions. The mechanism of the so called "redox signaling" includes H2O2-mediated reversible oxidation redox sensitive cysteine residues enzymes transcription factors thereby altering their activities. Depending on its intracellular concentration localization, H2O2 exhibits either pro- or anti-apoptotic In comparison to normal cells, cancer cells are characterized by an increased production rate impaired balance affecting microenvironment as well anti-tumoral immune response. This article reviews current knowledge about along with signaling mediating growth apoptosis tumor cells. addition it will be discussed how targeting H2O2-linked sources and/or components progression survival might lead novel therapeutic targets.

Language: Английский

Citations

495
The role of thiols in antioxidant systems DOI
Kathrin Ulrich,

Ursula Jakob

Free Radical Biology and Medicine, Journal Year: 2019, Volume and Issue: 140, P. 14 - 27

Published: June 13, 2019

Language: Английский

Citations

413
The multifaceted role of reactive oxygen species in tumorigenesis DOI
Anuradha Kirtonia, Gautam Sethi, Manoj Garg

et al.

Cellular and Molecular Life Sciences, Journal Year: 2020, Volume and Issue: 77(22), P. 4459 - 4483

Published: May 1, 2020

Language: Английский

Citations

391
Targeting the Thioredoxin System for Cancer Therapy DOI
Junmin Zhang, Xinming Li, Xiao Han

et al.

Trends in Pharmacological Sciences, Journal Year: 2017, Volume and Issue: 38(9), P. 794 - 808

Published: June 23, 2017

Language: Английский

Citations

383
Reactive Oxygen Species in Normal and Tumor Stem Cells DOI
Daohong Zhou, Lijian Shao, Douglas R. Spitz

et al.

Advances in cancer research, Journal Year: 2014, Volume and Issue: unknown, P. 1 - 67

Published: Jan. 1, 2014

Language: Английский

Citations

366
Xanthohumol ameliorates lipopolysaccharide (LPS)-induced acute lung injury via induction of AMPK/GSK3β-Nrf2 signal axis DOI Creative Commons
Hongming Lv,

Qinmei Liu,

Zhongmei Wen

et al.

Redox Biology, Journal Year: 2017, Volume and Issue: 12, P. 311 - 324

Published: March 2, 2017

Abundant natural flavonoids can induce nuclear factor-erythroid 2 related factor (Nrf2) and/or AMP-activated protein kinase (AMPK) activation, which play crucial roles in the amelioration of various inflammation- and oxidative stress-induced diseases, including acute lung injury (ALI). Xanthohumol (Xn), a principal prenylflavonoid, possesses anti-inflammation anti-oxidant activities. However, whether Xn could protect from LPS-induced ALI through inducing AMPK/Nrf2 activation its downstream signals, are still poorly elucidated. Accordingly, we focused on exploring protective effect context involvement underlying molecular mechanisms. Our findings indicated that effectively alleviated by reduction W/D ratio levels, neutrophil infiltration, MDA MPO formation, SOD GSH depletion. Meanwhile, significantly lessened histopathological changes, reactive oxygen species (ROS) generation, several cytokines secretion, iNOS HMGB1 expression, inhibited Txnip/NLRP3 inflammasome NF-κB signaling pathway activation. Additionally, evidently decreased t-BHP-stimulated cell apoptosis, ROS generation depletion but increased anti-oxidative enzymes expression regulated Keap1-Nrf2/ARE may be associated with AMPK GSK3β phosphorylation. Xn-mediated inflammatory production, WT mice were remarkably abrogated Nrf2-/- mice. experimental results firstly provided support protected against stress inflammation damage largely dependent upon upregulation Nrf2 via AMPK/GSK3β, thereby suppressing LPS-activated pathway.

Language: Английский

Citations

363
Beneficial and Detrimental Effects of Reactive Oxygen Species on Lifespan: A Comprehensive Review of Comparative and Experimental Studies DOI Creative Commons
Hazel J. Shields, Annika Traa, Jeremy M. Van Raamsdonk

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Feb. 11, 2021

Aging is the greatest risk factor for a multitude of diseases including cardiovascular disease, neurodegeneration and cancer. Despite decades research dedicated to understanding aging, mechanisms underlying aging process remain incompletely understood. The widely-accepted free radical theory (FRTA) proposes that accumulation oxidative damage caused by reactive oxygen species (ROS) one primary causes aging. To define relationship between ROS there have been two main approaches: comparative studies measure outcomes related across with different lifespans, experimental modulate levels within single using either genetic or pharmacologic approach. Comparative shown are inversely correlated lifespan. While these in general support FRTA, this type experiment can only demonstrate correlation, not causation. Experimental involving manipulation model organisms generally interventions increase tend decrease lifespan, while However, also multiple examples which opposite observed: increasing results extended longevity, decreasing shortened contradict predictions experiments performed very limited number species, all relatively short Overall, data suggest lifespan complex, both beneficial detrimental effects on longevity depending conditions. Accordingly, difficult generalize tree life.

Language: Английский

Citations

358
Reactive Oxygen Species in Macrophages: Sources and Targets DOI Creative Commons
Marcella Canton, Ricardo Sánchez‐Rodríguez, Iolanda Spera

et al.

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Sept. 30, 2021

Reactive oxygen species (ROS) are fundamental for macrophages to eliminate invasive microorganisms. However, as observed in nonphagocytic cells, ROS play essential roles processes that different from pathogen killing, signal transduction, differentiation, and gene expression. The outcomes of these events likely depend on the specific subcellular site formation, well duration extent production. While excessive accumulation has long been appreciated its detrimental effects, there is now a deeper understanding their signaling molecules. This could explain failure "all or none" pharmacologic approach with global antioxidants treat several diseases. NADPH oxidase first source identified macrophages. growing evidence highlights mitochondria crucial formation mainly due electron leakage respiratory chain enzymes, such monoamine oxidases. Their role redox signaling, together exact only partially elucidated. Hence, it identify intracellular sources how they influence cellular both physiological pathological conditions develop therapies targeting oxidative networks. In this review, we will focus sites impact metabolic inflammatory highlighting mitochondrial compared non-mitochondrial sources.

Language: Английский

Citations

262
The Prodrug Approach: A Successful Tool for Improving Drug Solubility DOI Creative Commons

Daniela Hartmann Jornada,

Guilherme Fernandes, Diego Eidy Chiba

et al.

Molecules, Journal Year: 2015, Volume and Issue: 21(1), P. 42 - 42

Published: Dec. 29, 2015

Prodrug design is a widely known molecular modification strategy that aims to optimize the physicochemical and pharmacological properties of drugs improve their solubility pharmacokinetic features decrease toxicity. A lack one main obstacles drug development. This review describe recent advances in improvement via prodrug approach. The chemical carriers examples successful strategies will be discussed, highlighting this field last ten years.

Language: Английский

Citations

256