p21rasas a Common Signaling Target of Reactive Free Radicals and Cellular Redox Stress

The paralogues RrpA and RrpB which are members of MarR family of DNA binding proteins are important for the survival of the global bacterial foodborne pathogen Campylobacter jejuni under redox stress. We report that RrpA is a positive regulator of mdaB , encoding a flavin-dependent quinone reductase that contributes to the protection from redox stress mediated by structurally diverse quinones, whilst RrpB negatively regulates the expression of cj1555c (renamed nfrA for NADPH-flavin reductase A), encoding a flavin reductase. NfrA reduces riboflavin at a greater rate than its derivatives, suggesting exogenous free flavins are the natural substrate. MdaB and NfrA both prefer NADPH as an electron donor. Cysteine substitution and post-translational modification analyses indicated that RrpA and RrpB employ a cysteine-based redox switch. Complete genome sequence analyses revealed mdaB is frequently found in Campylobacter and related Helicobacter spp ., whilst nfrA is predominant in C. jejuni strains. Quinones and flavins are redox cycling agents secreted by a wide range of cell-types that can form damaging superoxide by one-electron reactions. We propose a model for stress adaptation where MdaB and NfrA facilitate a two-electron reduction mechanism to the less toxic hydroquinones, thus aiding survival and persistence of this major pathogen. Importance Changes in cellular redox potential results in alteration in the oxidation state of intracellular metabolites and enzymes, consequently, cells make adjustments that favor growth and survival. The work we present here answers some of the many questions that have remained elusive over the years of investigation into the enigmatic microaerophile bacterium, Campylobacter jejuni . We employed molecular approaches to understand the regulation mechanisms and functional analyses to reveal the roles of two novel quinone and flavin reductases, both serve as major pools of cellular redox-active molecules. This work extends our knowledge on bacterial redox sensing mechanisms and the significance of hemostasis.

Download Full-text

The translocator protein (TSPO) is prodromal to mitophagy loss in neurotoxicity

Molecular Psychiatry ◽

10.1038/s41380-021-01050-z ◽

2021 ◽

Author(s):

Michele Frison ◽

Danilo Faccenda ◽

Rosella Abeti ◽

Manuel Rigon ◽

Daniela Strobbe ◽

...

Keyword(s):

Cell Death ◽

Transcription Factor ◽

Translocator Protein ◽

Redox Stress ◽

Cellular Redox ◽

Extracellular Signal ◽

Transcription Factor Eb ◽

Stress Susceptibility

AbstractDysfunctional mitochondria characterise Parkinson’s Disease (PD). Uncovering etiological molecules, which harm the homeostasis of mitochondria in response to pathological cues, is therefore pivotal to inform early diagnosis and therapy in the condition, especially in its idiopathic forms. This study proposes the 18 kDa Translocator Protein (TSPO) to be one of those. Both in vitro and in vivo data show that neurotoxins, which phenotypically mimic PD, increase TSPO to enhance cellular redox-stress, susceptibility to dopamine-induced cell death, and repression of ubiquitin-dependent mitophagy. TSPO amplifies the extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) signalling, forming positive feedback, which represses the transcription factor EB (TFEB) and the controlled production of lysosomes. Finally, genetic variances in the transcriptome confirm that TSPO is required to alter the autophagy–lysosomal pathway during neurotoxicity.

Download Full-text

EPR evidence of ROS, free radicals and lipid peroxidation produced in NMDA-stimulated PC-12 cells

Neuroscience Research ◽

10.1016/s0168-0102(00)81346-2 ◽

2000 ◽

Vol 38 ◽

pp. S83

Author(s):

Y Hayashi

Keyword(s):

Lipid Peroxidation ◽

Free Radicals ◽

Pc 12 Cells

Download Full-text

The high resolution absorption spectroscopy of aromatic free radicals

Journal de Chimie Physique ◽

10.1051/jcp/1964611517 ◽

1964 ◽

Vol 61 ◽

pp. 1517-1522 ◽

Cited By ~ 47

Author(s):

G. Porter ◽

B. Ward

Keyword(s):

Free Radicals ◽

High Resolution ◽

Absorption Spectroscopy

Download Full-text

Reduction potentials determination of some biochemically important free radicals. Pulse radiolysis and electrochemical methods

Journal de Chimie Physique ◽

10.1051/jcp/1993900711 ◽

1993 ◽

Vol 90 ◽

pp. 711-744 ◽

Cited By ~ 6

Author(s):

M Faraggi ◽

MH Klapper

Keyword(s):

Free Radicals ◽

Pulse Radiolysis ◽

Electrochemical Methods ◽

Reduction Potentials

Download Full-text

STRESS PADA LANSIA MENJADI FAKTOR PENYEBAB DAN AKIBAT TERJADINYA PENYAKIT

Journal of Health Sciences ◽

10.33086/jhs.v6i2.29 ◽

2015 ◽

Vol 6 (2) ◽

Author(s):

Nur Hidaayah

Keyword(s):

Drinking Water ◽

Free Radicals ◽

The Elderly ◽

The State ◽

Young Age ◽

Fresh Fruit ◽

Stress Conditions ◽

Harmful Substances ◽

Available Resources

Stress conditions in the elderly means an imbalance condition of biological, psychological, and social are closely related to the response to the threats and dangers faced by the elderly. Pressure or interference that is not fun is usually created when the elderly see a mismatch between the state and the 3 systems available resources. Maintenance actions that need to be done there are 2 types, namely : prevention of exposure to a stressor (precipitation factor) and serious treatment of the imbalance condition/ illness (precipitation factor). Prevention includes: sports, hobbies, friendship, avoid eating foods high in free radicals and harmful substances, sex and setting arrangements adequate rest. Habits of the above if done at a young age to avoid exposure to stress in the elderly. Treatment of the imbalance condition / illness, include : drinking water, meditation, eating fresh fruit, and adequate rest.

Download Full-text