ROS and p53: A versatile partnership

Abstract

The tumor suppressor protein p53 is a redox-active transcription factor that organizes and directs cellular responses in the face of a variety of stresses that lead to genomic instability. One of the most important questions in the study of p53 is how selective transactivation of certain p53 target genes is achieved. Reactive oxygen species (ROS), generated by cells as products or by-products, can function either as signaling molecules or as cellular toxicants. Cellular generation of ROS is central to redox signaling. Recent studies have revealed that each cellular concentration and distribution of p53 has a distinct cellular function and that ROS act as both an upstream signal that triggers p53 activation and a downstream factor that mediates apoptosis. Here, we examine the newly discovered role of p53 in regulating cellular ROS generation and how ROS modulate selective transactivation of p53 target genes. The focus is on interlinks between ROS and p53.

Iron overloaded polarizes macrophage to proinflammation phenotype through ROS/acetyl‐p53 pathway

“…The results of Prussian staining are shown in Figure 1A, and showed that macrophages could rapidly take up iron ion. Considering that previous studies have shown a relationship between intracellular iron concentration and macrophage polarization,3, 5 we measured the expression of IL‐1β, IL‐10, TNF‐α, and TGF‐β with Western blotting (Figure 1B), the result showed expression of IL‐1β and TNF‐α increased. The results of qRT‐PCR and flow cytometry are shown in Figure 1C,D, and showed that both Fe 2+ and Fe 3+ induced the expression of M1‐associated maker such as TNF‐α, CD86, and iNOS.…”

“…Aerobic cells can produce reactive oxygen species (ROS), which are mainly produced in the mitochondria, endoplasmic reticulum, plasma membrane, and cytosol under physiological conditions 3. Immunologically activated macrophages produce ROS, which are associated with enhanced antimicrobial activity 4.…”

Butyric acid retention in gingival tissue induces oxidative stress in jugular blood mitochondria

“…Moreover, our results would imply that BA effects in vitro and in vivo are consistent (Kurita-Ochiai and Ochiai 2010). ROS (like H 2 O 2 ) are generated as either as cellular products or by-products (Liu et al 2008;Valko et al 2006). ROS is commonly related to pathophysiological processes and has long been proposed to function in cell signaling (Suzuki et al 1997;Valko et al 2006;Zitomer and Lowry 1992).…”

15-Deoxy-Δ12,14-prostaglandin J2 stabilizes, but functionally inactivates p53 by binding to the cysteine 277 residue

“…Our site-directed mutagenesis experiment provides direct evidence that 15d-PGJ 2 can cause the modification of cysteine 277 in the human p53 protein. There are some reports in regard to the possibility of p53 stability by affecting on the conformation changes through redox modification (Velu et al, 2007;Liu et al, 2008). It is noticeable that there is cellular accumulation of oxidized p53 (Wu et al, 2000;Seemann and Hainaut, 2005).…”