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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Direct oxidative modifications of signalling proteins in mammalian cells and their effects on apoptosis
1Department of Biochemistry, Biosciences Institute, University College Cork, Cork, Ireland.
Abstract:
The production of ROS is an inevitable consequence of metabolism. However, high levels of ROS within a cell can be lethal and so the cell has a number of defences against oxidative cell stress. Occasionally the cell's antioxidant mechanisms fail and oxidative stress occurs. High levels of ROS within a cell have a number of direct and indirect consequences on cell signalling pathways and may result in apoptosis or necrosis. Although some of the indirect effects of ROS are well known, limitations in technology mean that the direct effects of the cell's redox environment upon proteins are less understood. Recent work by a number of groups has demonstrated that ROS can directly modify signalling proteins through different modifications, for example by nitrosylation, carbonylation, di-sulphide bond formation and glutathionylation. These modifications modulate a protein's activity and several recent papers have demonstrated their importance in cell signalling events, especially those involved in cell death/survival. Redox modification of proteins allows for further regulation of cell signalling pathways in response to the cellular environment. Understanding them may be critical for us to modulate cell pathways for our own means, such as in cytotoxic drug treatments of cancer cells. Protein modifications mediated by oxidative stress can modulate apoptosis, either through specific protein modifications resulting in regulation of signalling pathways, or through a general increase in oxidised proteins resulting in reduced cellular function. This review discusses direct oxidative protein modifications and their effects on apoptosis.
Insights
Reactive oxygen species (ROS) can harm cells, but cells have defenses. This review explores how ROS directly modify proteins, impacting cell signaling and apoptosis.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Cellular metabolism produces reactive oxygen species (ROS), essential signaling molecules.
- Excessive ROS can cause oxidative stress, leading to cell damage and death (apoptosis or necrosis).
- While indirect effects of ROS are known, direct impacts on proteins are less understood due to technological limitations.
Purpose of the Study:
- To review the direct effects of ROS on protein modifications.
- To elucidate the role of these modifications in cell signaling pathways.
- To understand the implications for apoptosis and potential therapeutic strategies.
Main Methods:
- Literature review of recent research on ROS-mediated protein modifications.
- Analysis of studies demonstrating direct protein modifications (nitrosylation, carbonylation, etc.).
- Examination of evidence linking these modifications to cell signaling and apoptosis.
Main Results:
- ROS can directly modify signaling proteins through various mechanisms like nitrosylation, carbonylation, disulfide bond formation, and glutathionylation.
- These modifications alter protein activity, influencing cell signaling events, particularly those related to cell death and survival.
- Redox modifications offer a regulatory layer for cell signaling in response to the cellular environment.
Conclusions:
- Direct protein modifications by ROS are crucial for regulating cell signaling pathways.
- Understanding these redox modifications is key to modulating cell pathways, with potential applications in cancer therapy.
- Oxidative stress-mediated protein changes can significantly impact apoptosis, either by altering specific signaling or by generally reducing cellular function.
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