Agmatine protects Müller cells from high-concentration glucose-induced cell damage via N-methyl-D-aspartic acid receptor inhibition

Abstract

Neural injury is associated with the development of diabetic retinopathy. Müller cells provide structural and metabolic support for retinal neurons. High glucose concentrations are known to induce Müller cell activity. Agmatine is an endogenous polyamine, which is enzymatically formed in the mammalian brain and has exhibited neuroprotective effects in a number of experimental models. The aims of the present study were to investigate whether agmatine protects Müller cells from glucose-induced damage and to explore the mechanisms underlying this process. Lactate dehydrogenase activity and tumor necrosis factor-α mRNA expression were significantly reduced in Müller cells exposed to a high glucose concentration, following agmatine treatment, compared with cells not treated with agmatine. In addition, agmatine treatment inhibited glucose-induced Müller cell apoptosis, which was associated with the regulation of Bax and Bcl-2 expression. Agmatine treatment suppressed glucose-induced phosphorylation of mitogen-activated protein kinase (MAPK) protein in Müller cells. The present study demonstrated that the protective effects of agmatine on Müller cells were inhibited by N-methyl-D-aspartic acid (NMDA). The results of the present study suggested that agmatine treatment protects Müller cells from high-concentration glucose-induced cell damage. The underlying mechanisms may relate to the anti-inflammatory and antiapoptotic effects of agmatine, as well as to the inhibition of the MAPK pathway, via NMDA receptor suppression. Agmatine may be of use in the development of novel therapeutic approaches for patients with diabetic retinopathy.

High Glucose-Induced Apoptosis in Human Kidney Cells Was Alleviated by miR-15b-5p Mimics

“…31) Lee et al found that HG could inhibit mTORC1 activity. 33) Our results verified this report by revealing that mTOR signaling pathway may be associated with HGinduced apoptosis in HK-2 cells. However, these effects were alleviated in the presence of miR-15b-5p mimics, demonstrating that miR-15b-5p mimics activated mTOR signaling pathway via increasing the level of p-Akt, p-mTOR and p-p70S6K.…”

Contribution of Müller Cells in the Diabetic Retinopathy Development: Focus on Oxidative Stress and Inflammation

“…These alterations lead to the activation of cell death pathways. Apoptosis is described due to a decrease in Bcl-2 and an increase in Bax (bcl2 associated X) and caspase-3 levels [173][174][175]. Recently, several studies have shown the activation of pyroptosis and mitophagy/autophagy pathways [169,[176][177][178][179][180].…”

Kir4.1 may represent a novel therapeutic target for diabetic retinopathy (Review)

“…On the other hand, AMPK is also crucial for the survival of Müller cells. In the high-glucose and hypoxia environment of DR, ensuring sufficient levels of Müller cells is needed in order to maintain the integrity of the blood-eye barrier, which may enhance the stability of the retinal microenvironment (82)(83)(84). A previous study has indicated that AMPK activation protects astrocytes from hypoxia-induced cell death (85).…”