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

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Abstract

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.

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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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Funding

The study was supported by Scientific Project Unit of Suleyman Demirel University, Isparta, Turkey. (Protocol No: BAP-4046-TU2 14).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey

    Elif İlknur Ekici & Mehmet Güney

  2. Department of Biophysics, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey

    Mustafa Nazıroğlu

  3. Drug Discovery Unit, BSN Health, Analysis and Innovation Ltd. Inc. Teknokent, Isparta, Turkey

    Mustafa Nazıroğlu

  4. Neuroscience Research Center, Suleyman Demirel University, TR-32260, Isparta, Turkey

    Mustafa Nazıroğlu

Authors
  1. Elif İlknur Ekici
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  2. Mehmet Güney
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Contributions

The study was summarized PhD thesis of EİE. Supervisors of the thesis were MG and MN. MG and MN formulated the present hypothesis and MN was responsible for writing the report. 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.

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Correspondence to Mustafa Nazıroğlu.

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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).

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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

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