Effect of Pentoxifylline on Staurosporine-Induced Neurite Elongation in PC12 Cells.

Loghman Diojan,Hossein Zhaleh,Ali Bidmeshkipour,Mehri Azadbakht,Ehsan Khodamoradi

doi:10.31557/apjcp.2019.20.9.2633

Abstract

Objective:Pentoxifylline enhances neurite elongation in PC12 cells. This study investigated the effects of pentoxifylline on staurosporine-induced neurite elongation in PC12 cells. Materials and Methods:There were five treatment groups, including treatment group I (1 nM), treatment group II (10 nM), treatment group III (100 nM), treatment group IV (1uM), and treatment group V (10 mM of pentoxifylline), together with 214 nM staurosporine for a range of time (6, 12 and 24 hours). Cells only treated with staurosporine at a concentration of 214 nM were used as the control group. Cell proliferation, cell death, immunocytochemistry assay, and Total Neurite Length were assessed.Results:The results showed that pentoxifylline increased cell viability (p<0.05) in a dose- and time-dependent manner, and cell death assay showed that cell death decreased in a dose- and time-dependent manner (p<0.05). TNL increased significantly compared with control cells (p<0.05). Immunocytochemistry assay showed that pentoxifylline at low and high concentrations enhanced β-tubulin III and GFAP protein expression compared with control cells. Conclusion:It can be concluded that pentoxifylline has positive effects on the staurosporine-induced neurite outgrowth process in PC12 cells.

Highlights

Staurosporine is a biological matter that induces neurite outgrowthat low concentrations and apoptosis at high concentrations in several cells (Schumacher et al, 2003; Das et al, 2004; Giuliano et al, 2004; Faghihi et al, 2008)
Lowest percentage of cell proliferation after 6 hours was seen in treatment group 1 (85%) and the highest was observed in treatment group 5 (115%) (p
We investigated the effect of pentoxifylline on staurosporine induced neurite outgrowth in PC12 cells

Summary

Introduction

Staurosporine is a biological matter that induces neurite outgrowthat low concentrations (nM) and apoptosis at high concentrations (μM) in several cells (Schumacher et al, 2003; Das et al, 2004; Giuliano et al, 2004; Faghihi et al, 2008). Previous studies have demonstrated that pentoxifylline may exert its effects through several mechanisms including translocation of extracellular calcium, increased cAMP and cyclic guanosine monophosphate (cGMP) caused by inhibition of phosphodiesterase, and blockade of adenosine receptors (Nasiri-Toosi et al, 2013; Speer et al, 2017) and cAMP overload pathway, resulting in cell viability and cell proliferation in neuronal cells (Cui and So, 2004; Hannila and Filbin, 2008). PTX and other PDE inhibitors exert their antiinflammatory/immunomodulatory activities by interfering with production of many cytokines (IL-4, IL-5, IL-10, TNF-α, IL-2 etc.) through inhibition of NF-kB and NFAT and stimulation of AP-1 and CREBs (cAMP response element binding proteins)(Hannila and Filbin, 2008). The results of a study by Sirin et al, (1998) showed that pentoxifylline reduces cerebral injury and preserves the neurologic function in transient global ischemia in rats

Methods

Results

Conclusion