Modulation of JAK2, STAT3 and Akt1 proteins by granulocyte colony stimulating factor following carbon monoxide poisoning in male rat

• Published in: Drug and chemical toxicology (New York, N.Y. 1978) N.Y. 1978), 2016-10, Vol.39 (4), p.375-379
• Main Authors: Hashemzaei, Mahmoud, Imen Shahidi, Mohsen, Moallem, Seyyed Adel, Abnous, Khalil, Ghorbani, Maryam, Mohamadpour, Amir Hooshang
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Carbon monoxide; Carbon Monoxide Poisoning - enzymology; Carbon Monoxide Poisoning - metabolism; Carbon Monoxide Poisoning - pathology; G-CSF; Granulocyte Colony-Stimulating Factor - administration & dosage; Granulocyte Colony-Stimulating Factor - pharmacology; heart; Injections, Subcutaneous; Janus Kinase 2 - metabolism; Male; Myocardium - enzymology; Myocardium - metabolism; Myocardium - pathology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - pathology; p-Akt1; p-JAK2; p-STAT3; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; rat; Rats, Wistar; STAT3 Transcription Factor - metabolism
• ISSN: 0148-0545; 1525-6014
• DOI: 10.3109/01480545.2015.1123267

Carbon monoxide (CO) is an odorless, colorless, tasteless and non-irritating by-product of inefficient combustion of hydrocarbon fuels such as motor vehicle exhausted gases. It is the leading cause of mortality in the USA among all unintentional toxicants. Male rats exposed to CO poisoning in the heart has many cardiovascular effects such as, cardiomyopathy, tachycardia, arrhythmias, and ischemia and in severe cases, myocardial infarction (MI) and cardiac arrest. Cardiomyocyte apoptosis is one of the most frequent consequences in the heart. Granulocyte colony stimulating factor (G-CSF) is a cytokine that mobilizes and differentiates granulocytes from stem cells. It can stimulate many anti-apoptotic pathways such as JAK2-STAT3 and PI3-Akt kinases following cardiac ischemia. G-CSF exerts its anti-apoptotic effects through binding to its specific cell surface receptor. The purpose of this study was to elucidate the mechanism of anti-apoptotic effect of G-CSF following CO poisoning. Rats were exposed to CO 1500 or 3000 ppm for 60 min. Animals received G-CSF 100 μg/kg subcutaneously for five consecutive days after CO intoxication. Western blot analysis was used to evaluate the expression of six proteins namely JAK2, p-JAK2, STAT3, p-STAT3, Akt1 and p-Akt1 following G-CSF 100 μg/kg consecutive dose administration after CO poisoning. There was a significant difference between phosphorylated proteins including p-JAK2, p-STAT3 and p-Akt1 in the G-CSF groups and those in control groups and there were not any significant differences in total protein among the groups.