18-kDa Translocator Protein Ligands Protect H9C2 Cardiomyocytes from Cigarette Smoke-induced Cell Death: In Vitro Study

Abstract

Background: Cigarette smoke (CS) can induce cellular damage via alterations in 18 kDa translocator protein (TSPO)-related functions, leading to cardiovascular diseases. The current study focused on the possible protective effect of TSPO ligands against CS-induced damage to cardiac cells. Materials and Methods: H9C2 Cardiomyocyte cell line of rat origin was pre-treated with TSPO ligands. Cell death, TSPO binding, and TSPO protein expression levels were assessed following 30-min CS exposure with/without TSPO ligands. Results: CS exposure of H9C2 cells significantly incensed cell death (by 26%, p<0.001). Pre-treatment with TSPO ligands at two concentrations prevented cell death. Neither CS nor ligands affected TSPO protein expression in H9C2 cells. CS led to increased cell death and reduced TSPO binding. Conclusion: Reduced TSPO binding may have a role in CS-induced cell death, and TSPO ligand MGV-1 can prevent suppression of TSPO binding and corresponding cell death. These results may be relevant to treatment of cardiovascular diseases associated with CS. 549

The Involvement of 18 kDa Translocator Protein (TSPO) in Cigarette Smoke-related Diseases: A Review

“…It was shown that exposure of cells to CS for prolonged time (30,60, and 120 mins) resulted in increases in TSPO expression levels [3]. As mentioned before, in contrast to this finding, Nagler et al, reported a decrease in binding levels of the TSPO ligand [ 3 H]PK 11195 after 30 minutes of exposure of cardiomyocytes [6] as well as in saliva samples exposed for 60 minutes to CS [56]. It is possible that the upregulation of TSPO protein expression is a consequence of its decreased binding capability.…”

“…In the cardiac tissue, the antioxidant system prevents oxidative damage to the myocardium by opposing the production of reactive oxygen species (ROS) [76]. Several studies reported on the impact of CS on TSPO and the TSPO-related mitochondrial processes, which eventually induce oxidative stress, and may cause cell death [3,6]. This association between CS exposure and the degree of the cellular damage was shown to correlate with increased ROS production, oxidative stress, and cell death in parallel to the CS exposure time.…”

“…Cigarette smoke (CS) is a main risk factor for the development of various diseases, either via direct exposure of tissues to CS [1][2][3] or indirect exposure of remote organs to CS extracts (CSE) (Figure 1) [4][5][6]. The harmful impact is induced by exposure to the toxic CS substances, each cigarette contains approximately 7,000 chemicals.…”

“…group assessed the impact of CS on the characteristics of [ 3 H]PK 11195 binding to TSPO in various tissues and cell lines. Some studies have shown that exposure to CS is associated with decreases in TSPO binding[6,53,56,64]. It appears that exposure to CS results in a decrease in TSPO binding.…”

The TSPO Ligands MGV-1 and 2-Cl-MGV-1 Differentially Inhibit the Cigarette Smoke-Induced Cytotoxicity to H1299 Lung Cancer Cells

“…In case of simultaneous treatment, the ligands were applied immediately at the time of placement of the plates into the CS chamber, while in case of post-CS exposure treatment the ligands were applied 1 h after CS exposure. The two ligands, MGV-1 and 2-Cl-MGV-1 (both at 25 µM), were chosen according to previous dose-response studies [ 37 , 38 ].…”