Protective effect of cabergoline on mitochondrial oxidative stress-induced apoptosis is mediated by modulations of TRPM2 in neutrophils of patients with endometriosis

Calcium ion (Ca2+) signaling in endometriosis (ENDO) is associated with increased neutrophil activation and oxidative stress. A Ca2+ signaling modulator and antioxidant actions of cabergoline (CBG) in some cells were recently reported. TRPM2 cation channel is activated by reactive oxygen species (ROS). Antioxidant action of CGB via inhibition of ROS may modulate the channel. We aimed to investigate the effect of CBG on TRPM2 inhibition in serum and neutrophils of patients with ENDO. The serum and neutrophil samples were grouped into healthy samples (no treatment), ENDO and ENDO + CBG treated groups (n = 10 in each). In some experiments, the neutrophils were also incubated with TRPM2 (ACA) and PARP-1 (PJ34) blockers. The values of intracellular ROS, Ca2+ concentration, mitochondrial membrane depolarization, lipid peroxidation, apoptosis, and caspase − 3, caspase − 9, PARP-1 and TRPM2 expressions were high in the neutrophils of patients with ENDO, although antioxidant levels (reduced glutathione, glutathione peroxidase, vitamin A, and vitamin E) were low in the neutrophils and serum from these patients. However, markers for apoptosis, oxidative stress, and mitochondrial dysfunction were reduced with CBG, ACA and PJ34 treatments, although the antioxidant levels were increased in the serum and neutrophils following treatment with CBG. Taken together, our current results suggest that CBG are useful antagonists against apoptosis and mitochondrial oxidative stress via inhibition of TRPM2 in neutrophils of patients with ENDO. Similar content being viewed by others Availability of data and materials The raw data files may be available upon request or as a supplementary file if the paper is accepted. Abbreviations - ACA: - N-(p-amylcinnamoyl) anthranilicacid - ADPR: - ADP-ribose - [Ca2+]i : - intracellular free Ca2+ - CBG: - cabergoline - DMSO: - dimethyl sulfoxide - fMLP: - N-formyl-L-methionyl-L-leucyl-phenylalanine - Fura-2/AM: - Fura 2-acetomethoxy ester - GPx: - glutathione peroxidase - GSH: - reduced glutathione - HBSS: - Hank's buffered salt solution - LiPx: - lipid peroxidation - MDA: - malondialdehyde - PARP-1: - poly ADP-ribose polymerase-1 - ROS: - reactive oxygen species - SDU: - Suleyman Demirel University - TRP: - transient receptor potential - TRPM2: - transient receptor potential melastatin 2

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Management of patients and blood collections form the patients were performed by EİE. MG made critical revision for the manuscript. All authors approved the final manuscript. Corresponding author Ethics declarations Conflict of interest We declared no conflict of interest in relation to this article. Ethics approval and informed consent The study was approved by the local human ethic committee of Suleyman Demirel University (Protocol number: 2014-085. Date: 06.04.2014). Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions About this article Cite this article Ekici, E.İ., Güney, M. & Nazıroğlu, M. Protective effect of cabergoline on mitochondrial oxidative stress-induced apoptosis is mediated by modulations of TRPM2 in neutrophils of patients with endometriosis. J Bioenerg Biomembr 52, 131–142 (2020). https://doi.org/10.1007/s10863-020-09830-y Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s10863-020-09830-y