Oxidation-reduction (redox) reactions are central to the existence of life. Reactive species of oxygen, nitrogen and sulfur mediate redox control of a wide range of essential cellular processes. Yet, Show more
Oxidation-reduction (redox) reactions are central to the existence of life. Reactive species of oxygen, nitrogen and sulfur mediate redox control of a wide range of essential cellular processes. Yet, excessive levels of oxidants are associated with ageing and many diseases, including cardiological and neurodegenerative diseases, and cancer. Hence, maintaining the fine-tuned steady-state balance of reactive species production and removal is essential. Here, we discuss new insights into the dynamic maintenance of redox homeostasis (that is, redox homeodynamics) and the principles underlying biological redox organization, termed the 'redox code'. We survey how redox changes result in stress responses by hormesis mechanisms, and how the lifelong cumulative exposure to environmental agents, termed the 'exposome', is communicated to cells through redox signals. Better understanding of the molecular and cellular basis of redox biology will guide novel redox medicine approaches aimed at preventing and treating diseases associated with disturbed redox regulation. Show less
Reactive sulfur species (RSS) entail a diverse family of sulfur derivatives that have emerged as important effector molecules in H2S-mediated biological events. RSS (including H2Show more
Reactive sulfur species (RSS) entail a diverse family of sulfur derivatives that have emerged as important effector molecules in H2S-mediated biological events. RSS (including H2S) can exert their biological roles via widespread interactions with metalloproteins. Metalloproteins are essential components along the metabolic route of oxygen in the body, from the transport and storage of O2, through cellular respiration, to the maintenance of redox homeostasis by elimination of reactive oxygen species (ROS). Moreover, heme peroxidases contribute to immune defense by killing pathogens using oxygen-derived H2O2 as a precursor for stronger oxidants. Coordination and redox reactions with metal centers are primary means of RSS to alter fundamental cellular functions. In addition to RSS-mediated metalloprotein functions, the reduction of high-valent metal centers by RSS results in radical formation and opens the way for subsequent per- and polysulfide formation, which may have implications in cellular protection against oxidative stress and in redox signaling. Furthermore, recent findings pointed out the potential role of RSS as substrates for mitochondrial energy production and their cytoprotective capacity, with the involvement of metalloproteins. The current review summarizes the interactions of RSS with protein metal centers and their biological implications with special emphasis on mechanistic aspects, sulfide-mediated signaling, and pathophysiological consequences. A deeper understanding of the biological actions of reactive sulfur species on a molecular level is primordial in H2S-related drug development and the advancement of redox medicine. Show less
Hydrogen peroxide (H2 O2 ) is an important reactive oxygen species that plays a major
role in redox signaling. Although H2 O2 is known to regulate gene expression and affect multiple
cellular processe Show more
Hydrogen peroxide (H2 O2 ) is an important reactive oxygen species that plays a major
role in redox signaling. Although H2 O2 is known to regulate gene expression and affect multiple
cellular processes, the characteristics and mechanisms of such transcriptional regulation remain to
be defined. In this study, we utilized transcriptome sequencing to determine the global changes of
mRNA and lncRNA transcripts induced by H2 O2 in human pancreatic normal epithelial (HPNE)
and pancreatic cancer (PANC-1) cells. Promoter analysis using PROMO and TRRUST revealed
that mRNAs and lncRNAs largely shared the same sets of transcription factors in response to ROS
stress. Interestingly, promoters of the upregulated genes were similar to those of the downregulated
transcripts, suggesting that the H2 O2 -responding promoters are conserved but they alone do not
determine the levels of transcriptional outputs. We also found that H2 O2 induced significant changes
in molecules involved in the pathways of RNA metabolism, processing, and transport. Detailed
analyses further revealed a significant difference between pancreatic cancer and noncancer cells in
their response to H2 O2 stress, especially in the transcription of genes involved in cell-cycle regulation
and DNA repair. Our study provides new insights into RNA transcriptional regulation upon ROS
stress in cancer and normal cells.
Transcription of mRNA and lncRNA.
Antioxidants 2022, 11, 495. https:// Show less
Significance: Oxidative stress is thought to account for aberrant redox homeostasis and contribute to aging and disease. However, more often than not, administration of antioxidants is ineffective, su Show more
Significance: Oxidative stress is thought to account for aberrant redox homeostasis and contribute to aging and disease. However, more often than not, administration of antioxidants is ineffective, suggesting that our current understanding of the underlying regulatory processes is incomplete. Recent Advances: Similar to reactive oxygen species and reactive nitrogen species, reactive sulfur species are now emerging as important signaling molecules, targeting regulatory cysteine redox switches in proteins, affecting gene regulation, ion transport, intermediary metabolism, and mitochondrial function. To rationalize the Show less