Cell Signaling by Protein Carbonylation and Decarbonylation

Abstract

Reactive oxygen species (ROS) serve as mediators of signal transduction. However, mechanisms of how ROS influence the target molecules to elicit signaling event have not been defined. Our laboratory recently accumulated evidence for the role of protein carbonylation in the mechanism of ROS signaling. This concept originated from experiments in which pulmonary artery smooth muscle cells were treated with endothelin-1 to understand the mechanism of cell growth. Endothelin-1 was found to promote protein carbonylation in an endothelin receptor- and Fenton reaction-dependent manner. Mass spectrometry identified proteins that are carbonylated in response to endothelin-1, including annexin A1. Our experiments generated a hypothesis that endothelin-1-mediated carbonylation and subsequent degradation of annexin A1 promote cell growth. This mechanism was found also to occur in response to other signaling activators such as serotonin and platelet-derived growth factor in smooth muscle cells of pulmonary circulation, systemic circulation, and the airway, as well as in cardiac muscle cells, suggesting the universal role of this pathway. We also discovered a process of decarbonylation that defines transient kinetics of carbonylation signals in certain conditions. We propose that protein carbonylation and decarbonylation serve as a mechanism of signal transduction.

Redox Signaling, Alkylation (Carbonylation) of Conserved Cysteines Inactivates Class I Histone Deacetylases 1, 2, and 3 and Antagonizes Their Transcriptional Repressor Function

“…Carbonylation is a marker of oxidative stress, and chronic exposure or elevated concentrations of RCS have been implicated in many diseases including, but not limited to, Alzheimer disease, chronic obstructive pulmonary disorder (60), arthritis, diabetes, and Parkinson disease, as reviewed by Dalle-Donne et al (61). Although aberrant modification and dysregulation of proteins have been the major focus of most protein carbonylation studies, it is becoming more evident that RCS may play an active role in redox signaling in ways analogous to ROSmediated signal transduction (62)(63)(64)(65) wt or HDAC1 C261S/C273S expression plasmids, and 24 h later, they were treated with either vehicle (VEH) or 15d-PGJ 2 (10 M). Cells were incubated for 24 h, and then mRNA expression analysis of HO-1, Gadd45, HSP70, and housekeeping genes GAPDH and ␤-actin were measured via reverse transcription-quantitative PCR.…”

Carbonylated proteins accumulated as vitality decreases during long-term storage of beech (Fagus sylvatica L.) seeds

“…Wong et al (2010) suggested that ROS produced by NAD(P)H oxidase elicit signal transduction and primary protein carbonylation mediates cell signaling. The ribulose-1,5-bisphosphate carboxylase oxygenase (RubisCO) large and small subunits (Muthuramalingam et al 2013) and malate dehydrogenase (MDH) ( Table 2) have been recently identified as proteins sensitive to H 2 O 2 .…”

“…Protein carbonyls seem to play roles in dormancy release and germination, as many proteins were carbonylated in Arabidopsis thaliana seeds during germination and these seeds were then successfully transformed into highly vigorous seedlings and young plants (Job et al 2005). For that reason, carbonylation is suspected to be a modification associated with several regulatory mechanisms; however, there is, as yet, no known decarbonylation reaction (Wong et al 2010). Specific enzymes associated with the regulation of the germination process can be carbonylated (Bailly et al 2008).…”

Proteomic evaluation of citrate-coated silver nanoparticles toxicity in Daphnia magna

“…11 Protein carbonyls are the most prevalent oxidative lesion of proteins 12 and there is growing evidence of their involvement in signal transduction. 13 They are also increasingly used as biomarkers of oxidative stress in ecotoxicological studies. 14,15 Despite their advantages, proteomics tools face a major challenge in ecotoxicology as the lack of genomic data for many species renders the identication of particular proteins affected by treatments difficult.…”