β2-Adrenergic Receptor Stimulation Upregulates Cx43 Expression on Glioblastoma Multiforme and Olfactory Ensheathing Cells

Hosseindoost, Saereh; Hashemizadeh, Shiva; Gharaylou, Zeinab; Dehpour, Ahmad Reza; Javadi, Seyed Amir Hossein; Arjmand, Babak; Hadjighassem, Mahmoudreza

doi:10.1007/s12031-020-01542-7

Cited by 13 publications

(13 citation statements)

References 52 publications

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“…To evaluate the effect of Cln on protein levels of Cx43, we measured the expression of Cx43 through western blot analysis. These results, similar to our previous findings, 35 show that Cln (10 μg/mL) could significantly increase the protein levels of Cx43 in GBM cells. Also, ICI at a concentration of 0.3 μg/mL blocked the Cln effect on Cx43 protein expression ( Figure 2 B).…”

Section: Resultssupporting

confidence: 92%

“…These results are consistent with our previous study, which revealed that Cln increased the Cx43 protein levels in the primary astrocytes and OECs. 35 Consistent with our results, other studies have shown that the signaling pathways induced by β2-AR stimulation lead to the upregulation of Cx43 levels in various cells. 33 , 34 , 44 , 45 , 46 Since Cx43 is the major structure of GJIC, which is an important factor in GCV-TP transmission, we evaluated the effect of Cln on apoptosis induction of HSV-TK/GCV gene therapy in GBM cells.…”

Section: Discussionsupporting

confidence: 93%

“…The previous results demonstrated that Cln as a β2-AR agonist could upregulate Cx43 expression in GBM cells and OECs. 35 Since the levels of the Cx43 and GJIC play a substantial role in mediating the bystander effect, in this section we evaluate the effect of Cln on the bystander effect between OEC-TK and GBM cells and the efficacy of HSV-TK/GCV suicide gene therapy of GBM cells. The OEC-TK and GBM cells were co-cultured at a ratio of 1:1 and incubated with GCV (2.5 μg/mL), Cln (10 μg/mL), and ICI (0.3 μg/mL) according to the grouping.…”

Section: Resultsmentioning

confidence: 99%

“… 33 , 34 Our previous study indicated that clenbuterol hydrochloride (Cln), a selective β2-AR agonist, enhanced the Cx43 expression levels in human GBM cells and OECs. 35 In this study, we hypothesize that the stimulation of β2-AR via the upregulation of Cx43 expression strengthens bystander effect and improves the gene therapy in GBM cells ultimately. This study aimed to evaluate the effect of Cln on the bystander effect between OEC-TK and GBM cells in HSV-TK/GCV suicide gene therapy using OECs as vectors.…”

Section: Introductionmentioning

confidence: 82%

“…In our previous study, we showed that β2-AR stimulation enhanced the Cx43 expression levels in human GBM cells and OECs. 35 In this study, we tried to demonstrate that targeting GBM tumor cells by OEC-HSV-TK/GCV in the presence of a β2-AR agonist enhanced the apoptotic effect of our construct.

Figure 7 Schematic diagram of bystander effect between OEC-TK and GBM cells and the effect of Cln on this phenomenon (A) The cells are connected by gap junction channels.…”

Section: Discussionmentioning

confidence: 99%

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β2-Adrenergic receptor agonist enhances the bystander effect of HSV-TK/GCV gene therapy in glioblastoma multiforme via upregulation of connexin 43 expression

Hosseindoost

Mousavi

Dehpour

et al. 2022

Molecular Therapy - Oncolytics

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Section: Resultssupporting

confidence: 92%

Section: Discussionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 82%

Figure 7 Schematic diagram of bystander effect between OEC-TK and GBM cells and the effect of Cln on this phenomenon (A) The cells are connected by gap junction channels.…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

β2-Adrenergic receptor agonist enhances the bystander effect of HSV-TK/GCV gene therapy in glioblastoma multiforme via upregulation of connexin 43 expression

Hosseindoost

Mousavi

Dehpour

et al. 2022

Molecular Therapy - Oncolytics

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Effect of tramadol on apoptosis and synaptogenesis in hippocampal neurons: The possible role of µ‐opioid receptor

Hosseindoost

Akbarabadi

Sadat‐Shirazi

et al. 2022

Drug Development Research

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Tramadol is a synthetic opioid with centrally acting analgesic activity that alleviates moderate to severe pain and treats withdrawal symptoms of the other opioids. Like other opioid drugs, tramadol abuse has adverse effects on central nervous system components. Chronic administration of tramadol induces maladaptive plasticity in brain structures responsible for cognitive function, such as the hippocampus. However, the mechanisms by which tramadol induces these alternations are not entirely understood. Here, we examine the effect of tramadol on apoptosis and synaptogenesis of hippocampal neuronal in vitro. First, the primary culture of hippocampal neurons from neonatal rats was established, and the purity of the neuronal cells was verified by immunofluorescent staining. To evaluate the effect of tramadol on neuronal cell viability MTT assay was carried out. The western blot analysis technique was performed for the assessment of apoptosis and synaptogenesis markers. Results show that chronic exposure to tramadol reduces cell viability of neuronal cells and naloxone reverses this effect. Also, the level of caspase‐3 significantly increased in tramadol‐exposed hippocampal neurons. Moreover, tramadol downregulates protein levels of synaptophysin and stathmin as synaptogenesis markers. Interestingly, the effects of tramadol were abrogated by naloxone treatment. These findings suggest that tramadol can induce neurotoxicity in hippocampal neuronal cells, and this effect was partly mediated through opioid receptors.

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Fluoxetine enhances the antitumor effect of olfactory ensheathing cell‐thymidine kinase/ganciclovir gene therapy in human glioblastoma multiforme cells through upregulation of Connexin43 levels

Hosseindoost,

Dehpour,

Dehghan

et al. 2023

Drug Development Research

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Glioblastoma multiforme (GBM) is the most invasive form of primary brain astrocytoma, resulting in poor clinical outcomes. Herpes simplex virus thymidine kinase/ganciclovir (HSV‐TK/GCV) gene therapy is considered a promising strategy for GBM treatment. Since Connexin43 (Cx43) expression is reduced in GBM cells, increasing Cx43 levels could enhance the effectiveness of gene therapy. The present study aims to examine the impact of fluoxetine on HSV‐TK/GCV gene therapy in human GBM cells using human olfactory ensheathing cells (OECs) as vectors. The effect of fluoxetine on Cx43 levels was assessed using the western blot technique. GBM‐derived astrocytes and OECs‐TK were Cocultured, and the effect of fluoxetine on the Antitumor effect of OEC‐TK/GCV gene therapy was evaluated using MTT assay and flow cytometry. Our results showed that fluoxetine increased Cx43 levels in OECs and GBM cells and augmented the killing effect of OECs‐TK on GBM cells. Western blot data revealed that fluoxetine enhanced the Bax/Bcl2 ratio and the levels of cleaved caspase‐3 in the coculture of OECs‐TK and GBM cells. Moreover, flow cytometry data indicated that fluoxetine increased the percentage of apoptotic cells in the coculture system. This study suggests that fluoxetine, by upregulating Cx43 levels, could strengthen the Antitumor effect of OEC‐TK/GCV gene therapy on GBM cells.

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β2-Adrenergic Receptor Stimulation Upregulates Cx43 Expression on Glioblastoma Multiforme and Olfactory Ensheathing Cells

Cited by 13 publications

References 52 publications

β2-Adrenergic receptor agonist enhances the bystander effect of HSV-TK/GCV gene therapy in glioblastoma multiforme via upregulation of connexin 43 expression

β2-Adrenergic receptor agonist enhances the bystander effect of HSV-TK/GCV gene therapy in glioblastoma multiforme via upregulation of connexin 43 expression

Effect of tramadol on apoptosis and synaptogenesis in hippocampal neurons: The possible role of µ‐opioid receptor

Fluoxetine enhances the antitumor effect of olfactory ensheathing cell‐thymidine kinase/ganciclovir gene therapy in human glioblastoma multiforme cells through upregulation of Connexin43 levels

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