Antioxidant responses and cellular adjustments to oxidative stress

Abstract

Redox biological reactions are now accepted to bear the Janus faceted feature of promoting both physiological signaling responses and pathophysiological cues. Endogenous antioxidant molecules participate in both scenarios. This review focuses on the role of crucial cellular nucleophiles, such as glutathione, and their capacity to interact with oxidants and to establish networks with other critical enzymes such as peroxiredoxins. We discuss the importance of the Nrf2-Keap1 pathway as an example of a transcriptional antioxidant response and we summarize transcriptional routes related to redox activation. As examples of pathophysiological cellular and tissular settings where antioxidant responses are major players we highlight endoplasmic reticulum stress and ischemia reperfusion. Topologically confined redox-mediated post-translational modifications of thiols are considered important molecular mechanisms mediating many antioxidant responses, whereas redox-sensitive microRNAs have emerged as key players in the posttranscriptional regulation of redox-mediated gene expression. Understanding such mechanisms may provide the basis for antioxidant-based therapeutic interventions in redox-related diseases.

On the vasoprotective mechanisms underlying novel β-phosphorylated nitrones: Focus on free radical characterization, scavenging and NO-donation in a biological model of oxidative stress

“…The concept of oxidative stress was recently re-defined as a disruption of redox signaling and control, a new perception that stimulated many investigations toward the role of cellular nucleophiles such as glutathione, or the identification of key enzymes perturbations [2][3][4]. Although it was now established that low levels of certain ROS can enhance cell defense capacity [2,5], there is a tremendous body of evidence from animal studies and clinical trials that a massive release of ROS contribute to the initiation and progression of a variety of chronic diseases such as inflammation, cancer, cardiovascular and neurodegenerative disorders, or acute iron overload-induced poisoning [1,6].…”

Role of the Transcription Factor Nrf2 in Parkinson’s Disease: New Insights

“…The first mechanism implicates the KEAP1 (Kelch-like ECH-associated protein 1)-dependent ubiquitination and degradation. KEAP1 is an ubiquitin E3 ligase substrate adapter for a Cullin3/Rbx1-dependent E3 ubiquitin ligase complex; henceforth binding of KEAP1 to NRF2 mediates ubiquitination and subsequent proteasomal degradation of NRF2 [47]. Interestingly, KEAP1 contains several cysteine residues capable of undergoing redox modifications and adduct formation with electrophilic compounds.…”

Hypoxia-Induced Molecular and Cellular Changes in the Congenitally Diseased Heart: Mechanisms and Strategies of Intervention

“…Nevertheless, the body is endowed with antioxidant enzymes such as catalase, glutathione peroxidase, and superoxide dismutase and vitamins (retinoic acid, alpha-tocopherol, ascorbic acid) that can counteract this physiological production [19]. Even in case of excessive free radical production, the body responds to restore harmony balance [20]. However, under chronic hypoxia, a downregulation of antioxidant defences occurs, making the cells vulnerable to oxidant damage.…”