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Oxidative stress and redox signaling in CRPC progression: therapeutic potential of clinically-tested Nrf2-activators

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Cancer Drug Resistance 2021年第1期4卷 96-124页

作者： Debasis Mondal Devin Narwani Shahnawaz Notta Dawood Ghaffar Nikhil Mardhekar Syed S.A.Quadri Debusk College of Osteopathic Medicine Lincoln Memorial UniversityKnoxvilleTN 37932USA

Androgen deprivation therapy(ADT)is the mainstay regimen in patients with androgen-dependent prostate cancer(PCa).However,the selection of androgen-independent cancer cells leads to castrate resistant prostate cancer(CRPC).The aggressive phenotype of CRPC cells underscores the need to elucidate mechanisms and therapeutic strategies to suppress CRPC *** ADT,the activation of androgen receptor(AR)transcription factor continues via crosstalk with parallel signaling *** of how these signaling cascades are initiated and amplified post-ADT is *** deprivation can increase oxidative stress and the resultant reactive oxygen species(ROS)may activate both AR and non-AR ***,ROS-induced inflammatory cytokines may further amplify these redox signaling pathways to augment AR ***,clinical trials using ROS quenching small molecule antioxidants have not suppressed CRPC progression,suggesting that more potent and persistent suppression of redox signaling in CRPC cells will be *** transcription factor Nrf2 increases the expression of numerous antioxidant enzymes and downregulates the function of inflammatory transcription factors,e.g.,nuclear factor kappa *** documented that Nrf2 overexpression can suppress AR-mediated transcription in CRPC cell ***,two Nrf2 activating agents,sulforaphane(a phytochemical)and bardoxolone-methyl(a drug in clinical trial)suppress AR levels and sensitize CRPC cells to *** observations implicate the benefits of potent Nrf2-activators to suppress the lethal signaling cascades that lead to CRPC *** review article will address the redox signaling networks that augment AR signaling during PCa progression to CRPC,and the possible utility of Nrf2-activating agents as an adjunct to ADT.

关键词： Prostate cancer androgen receptor hormone therapy endocrine resistance oxidative stress redox signaling Nrf2 Nrf2-activators

Abiotic stress-triggered oxidative challenges:Where does H_(2)S act?

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Journal of Genetics and Genomics 2022年第8期49卷 748-755页

作者： Linda de Bont Xiujie Mu Bo Wei Yi Han National Engineering Laboratory of Crop Stress Resistance Breeding School of Life SciencesAnhui Agricultural UniversityHefeiAnhui 230036China Universite de Lorraine INRAEIAMF-54000 NancyFrance School of Food and Biological Engineering Hefei University of TechnologyHefeiAnhui 230009China School of Biology Food and EnvironmentHefei UniversityHefeiAnhui 230601China

Hydrogen sulfide(H_(2)S)was once principally considered the perpetrator of plant growth cessation and cell ***,this has become an antiquated view,with cumulative evidence showing that the H_(2)S serves as a biological signaling molecule notably involved in abiotic stress response and adaptation,such as defense by phytohormone activation,stomatal movement,gene reprogramming,and plant growth *** oxygen species(ROS)-dependent oxidative stress is involved in these ***,an ever-growing body of evidence indicates that H_(2)S can directly interact with ROS processing systems in a redox-dependent manner,while it has been gradually recognized that H_(2)S-based posttranslational modifications of key protein cysteine residues determine stress ***,the reciprocal interplay between H_(2)S and nitric oxide(NO)in regulating oxidative stress has significant *** interaction of H_(2)S with NO and ROS during acclimation to abiotic stress may vary from synergism to ***,the molecular pathways and factors involved remain to be *** review not only aims to provide updated information on H_(2)S action in regulating ROS-dependent redox homeostasis and signaling,but also discusses the mechanisms of H_(2)S-dependent regulation in the context of oxidative stress elicited by environmental cues.

关键词： Hydrogen sulfide Oxidative stress ROS Nitric oxide redox signaling

Hydrogen sulfide, a signaling molecule in plant stress responses

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Journal of Integrative Plant Biology 2021年第1期63卷 146-160页

作者： Jing Zhang Mingjian Zhou Heng Zhou Didi Zhao Cecilia Gotor Luis CRomero Jie Shen Zhenglin Ge Zhirong Zhang Wenbiao Shen Xingxing Yuan Yanjie Xie Laboratory Center of Life Sciences College of Life SciencesNanjing Agricultural UniversityNanjing 210095China Instituto de Bioquimica Vegetal y Fotosintesis Consejo Superior de Investigaciones Cientfficas y Universidad de SevillaSevilla 41092Spain Institute of Industrial Crops Jiangsu Academy of Agricultural SciencesNanjing 210014China

Gaseous molecules, such as hydrogen sulfide(H_2S)and nitric oxide(NO), are crucial players in cellular and(patho)physiological processes in biological systems. The biological functions of these gaseous molecules, which were first discovered and identified as gasotransmitters in animals, have received unprecedented attention from plant scientists in recent decades. Researchers have arrived at the consensus that H_2S is synthesized endogenously and serves as a signaling molecule throughout the plant life ***, the mechanisms of H_2S action in redox biology is still largely unexplored. This review highlights what we currently know about the characteristics and biosynthesis of H_2S in plants. Additionally,we summarize the role of H_2S in plant resistance to abiotic stress. Moreover, we propose and discuss possible redox-dependent mechanisms by which H_2S regulates plant physiology.

关键词： gasotransmitter hydrogen sulfide persulfidation plant physiology redox signaling stress response

High intensity interval training and molecular adaptive response of skeletal muscle

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Sports Medicine and Health Science 2019年第1期1卷 24-32页

作者： Ferenc Torma Zoltan Gombos Matyas Jokai Masaki Takeda Tatsuya Mimura Zsolt Radak Research Center of Molecular Exercise Science University of Physical EducationBudapestHungary Faculty of Health and Sports Science Doshisha UniversityKyotanabeJapan Faculty of Sport and Health Sciences Osaka Sangyo UniversityOsakaJapan

Increased cardiovascular fitness,VO_(2max),is associated with enhanced endurance capacity and a decreased rate of *** intensity interval training(HIIT)is one of the best methods to increase VO_(2max)and endurance capacity for top athletes and for the general public as *** of the high intensity of this type of training,the adaptive response is not restricted to Type I fibers,as found for moderate intensity exercise of long *** with a short exercise duration,HIIT can induce activation of AMPK,PGC-1α,SIRT1 and ROS pathway as well as by the modulation of Ca^(2+)homeostasis,leading to enhanced mitochondrial biogenesis,and *** present review summarizes the current knowledge of the adaptive response of HIIT.

关键词： High intensity interval training Cellular adaptation Molecular pathways redox signaling Maximal oxygen uptake Mitochondrial biogenesis

Reactive oxygen species promote endurance exercise-induced adaptations in skeletal muscles

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Journal of Sport and Health Science 2024年第6期13卷 780-792页

作者： Scott K.Powers Zsolt Radak Li Li Ji Malcolm Jackson Department of Applied Physiology University of FloridaGainesvilleFL 32608USA Research Institute of Sport Science Hungarian University of Sport ScienceBudapest 1123Hungary Department of Kinesiology University of MinnesotaSt.PaulMN 55455USA Department of Musculoskeletal and Ageing Science Institute of Life Course and Medical SciencesUniversity of LiverpoolLiverpool L78TXUK

The discovery that contracting skeletal muscle generates reactive oxygen species(ROS)was first reported over 40 years *** prevailing view in the 1980s was that exercise-induced ROS production promotes oxidation of proteins and lipids resulting in muscle ***,a paradigm shift occurred in the 1990s as growing research revealed that ROS are signaling molecules,capable of activating transcriptional activators/coactivators and promoting exercise-induced muscle *** evidence supports the notion that reduction-oxidation(redox)signaling pathways play an important role in the muscle remodeling that occurs in response to endurance exercise *** review examines the specific role that redox signaling plays in this endurance exercise-induced skeletal muscle *** begin with a discussion of the primary sites of ROS production in contracting muscle fibers followed by a summary of the antioxidant enzymes involved in the regulation of ROS levels in the *** then discuss which redox-sensitive signaling pathways promote endurance exercise-induced muscle adaptation and debate the strength of the evidence supporting the notion that redox signaling plays an essential role in muscle adaptation to endurance exercise *** hopes of stimulating future research,we highlight several important unanswered questions in this field.

关键词： Antioxidants Mitochondrial biogenesis Radicals redox signaling

AUTOCRINE ACTIONS OF NADPH OXTOASE-DERIVED O2-IN CORONARY ARTERIAL MYOCYTES

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AUTOCRINE ACTIONS OF NADPH OXTOASE-DERIVED O2-IN CORONARY AR...