Expression of C-fos, Fos-B, Fosl-1, Fosl-2, Dusp-1 and C-jun in the mouse heart after single and repeated chlorpromazine administrations.
Many cases of sudden chlorpromazine (Chl)-related deaths have been identified in forensic autopsies. Because Chl concentration detected in such cases is often low, identifying the cause of death can be difficult. Patients on Chl therapy exhibit arrhythmia and cardiomyopathy. Thus, Chl may affect the heart, particularly, gene expression there. Immediate early genes (IEGs) are expressed following stimulation. Using real-time quantitative-PCR, we investigated the mRNA expression of IEGs, including C-fos, Fos-B, Fosl-1, Fosl-2, Dusp-1 and C-jun, in the mouse heart after once-daily high-dose (7.5 mg/kg) or low-dose (0.75 mg/kg) of Chl single and repeated (1-4 weeks) injections. We showed that single high-dose Chl administration induced IEGs except C-jun. This induction was not observed after the repeated administration, and thus; suggested that the transcriptome is altered after repeated administration and tolerance is developed to Chl. Moreover, C-jun expression decreases after repeated administration. These results reflect that C-jun is down-regulated to avoid cardiomyopathy caused by the over stimulation of C-jun. In future, we intend to clarify the Chl-induced IEG cascade via IEGs in the mouse heart. Chl treatment can result in cardiovascular diseases. Investigation of the transcriptome in the heart after repeated Chl administration will aid in elucidating the patho-physiology of Chl-related cardiovascular diseases.
Sakai
Sayaka
S
School of Medicine, Nagasaki University, Japan.
Ikematsu
Kazuya
K
Matsuo
Aya
A
Tsai
Chung-Ting
CT
Nakasono
Ichiro
I
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000506:poisoning; D002746:Chlorpromazine / Q000494:pharmacology* / Q000506:poisoning; D015870:Gene Expression / Q000187:drug effects*; D017781:Genes, Immediate-Early / Q000235:genetics; D016762:Genes, fos / Q000187:drug effects*; D016758:Genes, jun / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D014150:Antipsychotic Agents; D002746:Chlorpromazine