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An Optogenetic Method to Control and Analyze Gene Expression Patterns in Cell-to-cell Interactions
Published on: March 22, 2018
Oxidative-dependent integration of signal transduction with intercellular gap junctional communication in the control
1Department of Pediatrics and Human Development, National Food Safety and Toxicology Center, Michigan State University, East Lansing, Michigan 48824, USA. upham@msu.edu
Abstract:
Research on oxidative stress focused primarily on determining how reactive oxygen species (ROS) damage cells by indiscriminate reactions with their macromolecular machinery, particularly lipids, proteins, and DNA. However, many chronic diseases are not always a consequence of tissue necrosis, DNA, or protein damage, but rather to altered gene expression. Gene expression is highly regulated by the coordination of cell signaling systems that maintain tissue homeostasis. Therefore, much research has shifted to the understanding of how ROS reversibly control gene expression through cell signaling mechanisms. However, most research has focused on redox regulation of signal transduction within a cell, but we introduce a more comprehensive-systems biology approach to understanding oxidative signaling that includes gap junctional intercellular communication, which plays a role in coordinating gene expression between cells of a tissue needed to maintain tissue homeostasis. We propose a hypothesis that gap junctions are critical in modulating the levels of second messengers, such as low molecular weight reactive oxygen, needed in the transduction of an external signal to the nucleus in the expression of genes. Thus, any comprehensive-systems biology approach to understanding oxidative signaling must also include gap junctions, in which aberrant gap junctions have been clearly implicated in many human diseases.
Insights
Oxidative stress impacts gene expression via cell signaling. This study proposes a systems biology approach, incorporating gap junctions, to understand how reactive oxygen species (ROS) reversibly control cellular communication and gene expression, crucial for tissue homeostasis.
Area of Science:
- Cellular Biology
- Molecular Biology
- Systems Biology
Background:
- Oxidative stress research traditionally focused on reactive oxygen species (ROS) causing direct cellular damage.
- Chronic diseases often stem from altered gene expression rather than direct cellular necrosis.
- Cell signaling pathways regulate gene expression and maintain tissue homeostasis.
Purpose of the Study:
- To explore how ROS reversibly control gene expression through cell signaling mechanisms.
- To introduce a comprehensive systems biology approach to oxidative signaling.
- To investigate the role of gap junctional intercellular communication in oxidative signaling.
Main Methods:
- Review of existing research on oxidative stress and cell signaling.
- Hypothesis formulation regarding the role of gap junctions in oxidative signaling.
- Systems biology conceptual framework integrating intercellular communication.
Main Results:
- Reactive oxygen species (ROS) reversibly regulate gene expression via cell signaling.
- Gap junctions are proposed as critical modulators of second messengers in oxidative signal transduction.
- Aberrant gap junctions are implicated in various human diseases.
Conclusions:
- A comprehensive understanding of oxidative signaling requires a systems biology approach.
- Gap junctional intercellular communication is vital for coordinating gene expression and maintaining tissue homeostasis.
- Future research should integrate gap junction function into models of oxidative stress and disease.
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