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

Abstract

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.

Neuro‐Protective Effects of Resveratrol on Carbon Monoxide‐Induced Toxicity in Male Rats

“…In a study done by Gang Lu and colleague, it was shown that global ischemia increases BAX/BCL2 ratio (Lu et al, 2006). Furthermore, several reports have confirmed that CO poisoning results in induction of apoptosis (Ghorbani et al, 2017;Hashemzaei et al, 2016b;Weaver, 2009). Our findings are consistent with the data obtained in other studies because CO poisoning induces global ischemia and RES can reduce apoptosis.…”

“…Our previous study showed that RES could ameliorate CO‐induced cardiovascular effects in an animal model (Hashemzaei et al , ). In order to find new substances that can fight the deleterious effects of CO poisoning in the heart and brain and also to shed light on the underlying mechanisms, in our previous studies, we discussed the involved pathways (Ghorbani et al , ; Hashemzaei et al , ; Mohamadpour et al , ). To the best of our knowledge, it is for the first time that the neuroprotective effect of multiple‐dose RES administration on CO poisoning is evaluated in rats.…”

“…In order to find new substances that can fight the deleterious effects of CO poisoning in the heart and brain and also to shed light on the underlying * Correspondence to: Mahmoud Hashemzaei, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran. E-mail: mhtoxicologist@gmail.com mechanisms, in our previous studies, we discussed the involved pathways (Ghorbani et al, 2017;Hashemzaei et al, 2016b;Mohamadpour et al, 2012). To the best of our knowledge, it is for the first time that the neuroprotective effect of multiple-dose RES administration on CO poisoning is evaluated in rats.…”

Application of G-CSF in Congestive Heart Failure Treatment

“…In other words, G-CSF therapy led to cardiac protection due to its effect on increasing phosphorylated proteins. In addition, G-CSF reduces transcription of apoptosis-inducing proteins such as Bad and caspase 3 [ 19 ] It is expected that after MI about one-half of all patients develop CHF and is characteristic for acute changes in LV function [ 20 ]. Accordingly, G-CSF can improve the function of a chronic failed heart.…”

Anti‑hypertensive effect of crocin and hesperidin combination in high‑fat diet treated rats

“…Natural products are small molecules produced by organisms as primary and secondary metabolites and they exert various useful properties including anti-oxidant, anti-inflammatory, cancer preventive, cardiovascular, anti-Alzheimer's, platelet modulatory and pain relief effects (1)(2)(3)(4)(5).…”