Cell signaling (mechanism and reproductive toxicity): redox chains, radicals, electrons, relays, conduit, electrochemistry, and other medical implications.
This article deals with a novel, simple, integrated approach to cell signaling involving basic biochemical principles, and their relationship to reproductive toxicity. Initially, an overview of the biological aspects is presented. According to the hypothetical approach, cell signaling entails interaction of redox chains, involving initiation, propagation, and termination. The messengers are mainly radicals and electrons that are generated during electron transfer (ET) and hydrogen atom abstraction reactions. Termination and initiation processes in the chain occur at relay sites occupied by redox functionalities, including quinones, metal complexes, and imines, as well as redox amino acids. Conduits for the messengers, comprising species with nonbonding electrons, are omnipresent. Details are provided for the various electron transfer processes. In relation to the varying rates of cell communication, rationale is based on electrons and size of radicals. Another fit is similarly seen in inspection of endogenous precursors of reactive oxygen species (ROS); namely, proteins bearing redox moieties, lipid oxidation products, and carbohydrate radicals. A hypothesis is advanced in which electromagnetic fields associated with mobile radicals and electrons play a role. Although radicals have previously been investigated as messengers, the area occupies a minor part of the research, and it has not attracted broad consensus as an important component. For the first time, an integrated framework is presented composed of radicals, electrons, relays, conduits, and electrical fields. The approach is in keeping with the vast majority of experimental observations. Cell signaling also plays an important role in reproductive toxicity. The main classes that cause birth defects, including ROS, radiation, metal compounds, medicinals, abused drugs, and miscellaneous substances, are known to participate in the signaling process. A unifying basis exists, in that both signaling and reproductive toxicity are characterized by the electron transfer-reactive oxygen species-oxidative stress (ET-ROS-OS) scheme. This article also incorporates representative examples of the extensive investigations dealing with various medical implications. There is considerable literature pointing to a role for cell communication in a wide variety of illnesses.
Kovacic
Peter
P
Department of Chemistry, San Diego State University, San Diego, California 92182-1030, USA. pkovacic@sundown.sdsu.edu
Pozos
Robert S
RS
D000014:Abnormalities, Drug-Induced / Q000209:etiology / Q000378:metabolism; D000818:Animals; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology* / Q000528:radiation effects; D064420:Drug-Related Side Effects and Adverse Reactions; D004563:Electrochemistry; D004583:Electrons; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D013287:Illicit Drugs / Q000633:toxicity; D008670:Metals / Q000633:toxicity; D008954:Models, Biological; D010084:Oxidation-Reduction; D011247:Pregnancy; D012098:Reproduction / Q000187:drug effects* / Q000502:physiology* / Q000528:radiation effects; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology* / Q000528:radiation effects
D005609:Free Radicals; D013287:Illicit Drugs; D008670:Metals