Oxidative-dependent integration of signal transduction with intercellular gap junctional communication in the control of gene expression.
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.
Upham
Brad L
BL
Department of Pediatrics and Human Development, National Food Safety and Toxicology Center, Michigan State University, East Lansing, Michigan 48824, USA. upham@msu.edu
Trosko
James E
JE
D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D017629:Gap Junctions / Q000378:metabolism* / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D017382:Reactive Oxygen Species