Abstract
Arsenite is known to chemically modify cysteine residues in proteins, with a preference for dithiols. This chapter identifies some of the roles that arsenic plays in signal transduction pathways. Reactive oxygen species (ROS) have the ability to activate signal transduction pathways as part of normal system physiology. G-protein-coupled receptors (GPCR) consist of seven transmembrane domains that bind ligands and transduce signals into the cell. Due to the growth-promoting activity associated with prostanoids, arsenic-dependent expression of cyclooxygenase-2 (Cox-2) was investigated in normal human epidermal keratinocytes.An analysis of the glucocorticoid receptor domains indicated that arsenite-dependent modulation of transcription targeted the central DNA-binding domain. When researchers first began investigating the role of mitogen-activated protein (MAP) kinases in arsenic signaling, the studies often used nonphysiologically relevant doses of arsenic. The phosphatidylinositol 3-kinase (PI3-K) pathway also plays an important role in arsenic-dependent regulation of p53 DNA-binding activity.
| Original language | English (US) |
|---|---|
| Title of host publication | Arsenic |
| Subtitle of host publication | Exposure Sources, Health Risks, and Mechanisms of Toxicity |
| Publisher | Wiley |
| Pages | 369-396 |
| Number of pages | 28 |
| ISBN (Electronic) | 9781118876992 |
| ISBN (Print) | 9781118511145 |
| DOIs | |
| State | Published - Oct 30 2015 |
Keywords
- Arsenic
- Cyclooxygenase-2
- Cysteine residues
- DNA-binding activity
- G-protein-coupled receptors
- Mitogen-activated protein kinases
- Nuclear receptors
- Phosphatidylinositol 3-kinase
- Reactive oxygen species
- Signal transduction
ASJC Scopus subject areas
- Chemistry(all)
- Pharmacology, Toxicology and Pharmaceutics(all)
- Engineering(all)
- Medicine(all)