title: Off-Target drug effects resulting in altered gene expression events with epigenetic and "Quasi-Epigenetic" origins.
abstract: This review synthesizes examples of pharmacological agents who have off-target effects of an epigenetic nature. We expand upon the paradigm of epigenetics to include "quasi-epigenetic" mechanisms. Quasi-epigenetics includes mechanisms of drugs acting upstream of epigenetic machinery or may themselves impact transcription factor regulation on a more global scale. We explore these avenues with four examples of conventional pharmaceuticals and their unintended, but not necessarily adverse, biological effects. The quasi-epigenetic drugs identified in this review include the use of beta-lactam antibiotics to alter glutamate receptor activity and the action of cyclosporine on multiple transcription factors. In addition, we report on more canonical epigenome changes associated with pharmacological agents such as lithium impacting autophagy of aberrant proteins, and opioid drugs whose chronic use increases the expression of genes associated with addictive phenotypes. By expanding our appreciation of transcriptomic regulation and the effects these drugs have on the epigenome, it is possible to enhance therapeutic applications by exploiting off-target effects and even repurposing established pharmaceuticals. That is, exploration of "pharmacoepigenetic" mechanisms can expand the breadth of the useful activity of a drug beyond the traditional drug targets such as receptors and enzymes.
authors.affiliation: Department of Psychology, Iowa State University College of Liberal Arts and Sciences, Ames, IA 50011, United States; Neuroscience Interdepartmental Program, Iowa State University, Ames, IA 50011, United States.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Anderson
authors.affiliation: Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA 50011, United States.
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Feye
authors.affiliation: Neuroscience Interdepartmental Program, Iowa State University, Ames, IA 50011, United States; Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA 50011, United States.
authors.forename: Garrett R
authors.initials: GR
authors.lastname: Schmidt-McCormack
authors.affiliation: Neuroscience Interdepartmental Program, Iowa State University, Ames, IA 50011, United States.
authors.forename: Emir
authors.initials: E
authors.lastname: Malovic
authors.affiliation: Neuroscience Interdepartmental Program, Iowa State University, Ames, IA 50011, United States; Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA 50011, United States.
authors.forename: Gregory S A
authors.initials: GSA
authors.lastname: Mlynarczyk
authors.affiliation: Neuroscience Interdepartmental Program, Iowa State University, Ames, IA 50011, United States.
authors.forename: Patricia
authors.initials: P
authors.lastname: Izbicki
authors.affiliation: Department of Psychology, Iowa State University College of Liberal Arts and Sciences, Ames, IA 50011, United States; Neuroscience Interdepartmental Program, Iowa State University, Ames, IA 50011, United States.
authors.forename: Larissa F
authors.initials: LF
authors.lastname: Arnold
authors.affiliation: Department of Kinesiology, Iowa State University College of Liberal Arts and Sciences, Ames, IA 50011, United States.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Jefferson
authors.affiliation: Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA 50011, United States.
authors.forename: Bierlein M
authors.initials: BM
authors.lastname: de la Rosa
authors.affiliation: Department of Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA 50011, United States.
authors.forename: Rita F
authors.initials: RF
authors.lastname: Wehrman
authors.affiliation: Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA 50011, United States.
authors.forename: K C
authors.initials: KC
authors.lastname: Luna
authors.affiliation: Neuroscience Interdepartmental Program, Iowa State University, Ames, IA 50011, United States.
authors.forename: Hilary Z
authors.initials: HZ
authors.lastname: Hu
authors.affiliation: Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA 50011, United States.
authors.forename: Naveen C
authors.initials: NC
authors.lastname: Kondru
authors.affiliation: Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA 50011, United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Kleinhenz
authors.affiliation: Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA 50011, United States.
authors.forename: Joe S
authors.initials: JS
authors.lastname: Smith
authors.affiliation: Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA 50011, United States.
authors.forename: Sireesha
authors.initials: S
authors.lastname: Manne
authors.affiliation: Neuroscience Interdepartmental Program, Iowa State University, Ames, IA 50011, United States.
authors.forename: Marson R
authors.initials: MR
authors.lastname: Putra
authors.affiliation: Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA 50011, United States.
authors.forename: Shivani
authors.initials: S
authors.lastname: Choudhary
authors.affiliation: Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA 50011, United States.
authors.forename: Nyzil
authors.initials: N
authors.lastname: Massey
authors.affiliation: Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA 50011, United States.
authors.forename: Diou
authors.initials: D
authors.lastname: Luo
authors.affiliation: Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA 50011, United States.
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Berg
authors.affiliation: Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA 50011, United States.
authors.forename: Sreemoyee
authors.initials: S
authors.lastname: Acharya
authors.affiliation: Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA 50011, United States.
authors.forename: Shaunik
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA 50011, United States.
authors.forename: Sri Harsha
authors.initials: SH
authors.lastname: Kanuri
authors.affiliation: Department of Kinesiology, Iowa State University College of Liberal Arts and Sciences, Ames, IA 50011, United States.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Lange
authors.affiliation: Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA 50011, United States. Electronic address: stevec@iastate.edu.
authors.forename: Steve A
authors.initials: SA
authors.lastname: Carlson
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000235:genetics; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018020:Lithium Compounds / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D011957:Receptors, Opioid / Q000378:metabolism; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D027322:Amino Acid Transport System X-AG; D000701:Analgesics, Opioid; D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; D018020:Lithium Compounds; D018696:Neuroprotective Agents; D011957:Receptors, Opioid; D047090:beta-Lactams; D016572:Cyclosporine