σ-1 receptor stimulation protects against pressure-induced damage through InsR-MAPK signaling in human trabecular meshwork cells

Meng,Bo; Li,Hongyi; Sun,Xian; Qu,Wei; Yang,Binbin; Cheng,Fang; Shi,Liping; Yuan,Huiping

doi:10.3892/mmr.2017.6647

σ-1 receptor stimulation protects against pressure-induced damage through InsR-MAPK signaling in human trabecular meshwork cells

Authors:
- Bo Meng
- Hongyi Li
- Xian Sun
- Wei Qu
- Binbin Yang
- Fang Cheng
- Liping Shi
- Huiping Yuan
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Affiliations: Department of Ophthalmology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China, Department of Ophthalmology and Otorhinolaryngology, Hospital of Heilongjiang University, Harbin, Heilongjiang 150080, P.R. China, Department of Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China
Published online on: May 30, 2017 https://doi.org/10.3892/mmr.2017.6647
Pages: 617-624
Copyright: © Meng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The purpose of the present study was to investigate the protective effect of the σ-1 receptor (Sig-1R) agonist (+)‑pentazocin (PTZ) on pressure-induced apoptosis and death of human trabecular meshwork cells (hTMCs). The expression levels of Sig‑1R and insulin receptor (InsR) were examined in hTMCs. Cells were cultured under a pressure of 0, 20, 40, 60 and 80 mmHg for 48 h, and under 80 mmHg for 44 h, after which the cells were treated with (+)‑PTZ (20 µM), N-(2-(3,4-dichlorophenyl)ethyl)-N‑methyl-2‑(dimethylamino) ethylamine (BD‑1063; 20 µM) administered 30 min prior to (+)‑PTZ, or BD‑1063 (20 µM) and then exposed to 80 mmHg again until the 48 h time‑point. The changes of the cells were observed by optical and electron microscopy, the apoptosis and death of hTMCs were detected by ethidium bromide/acridine orange dual staining assay and the expression of Sig‑1R and InsR by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The phosphorylation of extracellular signal‑regulated kinase (ERK), an important downstream protein of the InsR‑mitogen‑activated protein kinases (MAPK) signaling pathway, was also detected by western blot analysis when (+)‑PTZ and BD‑1063 were added to the 80 mmHg‑treated cells. Sig‑1Rs and InsRs were expressed in hTMCs. The apoptosis and death of hTMCs increased from 40 mmHg with 50% cell death when the pressure was at 80 mmHg and the structure of the cells noticeably changed. The expression of Sig‑1R and InsR increased along with the elevation of pressure. (+)‑PTZ decreased the apoptosis and death of hTMCs and increased the expression of Sig‑1R and InsR, and the phosphorylation of ERK. Such effects were blocked by BD‑1063. The present study suggested that Sig‑1R agonist (+)‑PTZ can protect hTMCs from pressure‑induced apoptosis and death by activating InsR and the MAPK signal pathway.

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