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Hypericum perforatum Modulates Apoptosis and Calcium Mobilization Through Voltage-Gated and TRPM2 Calcium Channels in Neutrophil of Patients with Behcet’s Disease

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Abstract

Behcet’s disease (BD) is a chronic, inflammatory, and multisystemic condition although its pathogenesis is uncertain. Main component of St. John’s wort (Hypericum perforatum, HP) is hyperforin and induces antiinflammatory and antioxidant properties. We aimed to investigate effects of HP on oxidative stress, apoptosis, and cytosolic-free Ca2+ [Ca2+]i concentration in neutrophil of BD patients. Nine new-diagnosed active patients with BD and nine control subjects were included in the study. Disease activity was considered by clinical findings. Neutrophil samples were obtained from the patients and controls. The neutrophils from patients were divided into three subgroups and were incubated with HP, voltage-gated calcium channel (VGCC) blockers, (verapamil+dilitiazem) and non-specific TRPM2 channel blocker (2-aminoethyl diphenylborinate, 2-APB), respectively. The neutrophils were stimulated by fMLP as a Ca2+-concentration agonist and oxidative stress former. Caspase-3, caspase-9, apoptosis, lipid peroxidation, and [Ca2+]i values were high in the patient groups, although cell viability, glutathione (GSH), and glutathione peroxidase (GSH-Px) values were low in patient group. However, the [Ca2+]i, caspase-3, and caspase-9 values decreased markedly in patient+HP group although GSH and GSH-Px values increased in the group. The [Ca2+]i concentration was also decreased in the patient group by V+D, 2-APB, and HP incubations. In conclusion, we observed the importance of neutrophil Ca2+ entry, apoptosis, and oxidative stress through gating VGCC and TRPM2 channels in the neutrophils in the pathogenesis and activation of the patients with BD. HP induced protective effects on oxidative stress by modulating Ca2+ influx in BD patients.

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Abbreviations

2-APB:

2-Aminoethyl diphenylborinate

BD:

Behcet’s disease

CRP:

C-reactive protein

ESR:

Erythrocyte sedimentation rate

fMLP:

N-Formyl-l-methionyl-l-leucyl-l-phenylalanine

GSH:

Reduced glutathione

GSH-Px:

Glutathione peroxidase

MDA:

Malondialdehyde

MPO:

Myeloperoxidase

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

TRPM2:

Transient receptor potential melastatin 2

V+D:

Verapamil+diltiazem

VGCC:

Voltage-gated calcium channels

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Acknowledgments

MN formulated the present hypothesis and was responsible for writing the report. BÇ and MA were responsible from analysis. Blood samples and detection of the disease were performed by MŞ, İE, and YU. The study was partially supported by Unit of Scientific Research Project, Suleyman Demirel University (NO: BAP: 2526-M-10).

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  1. Mustafa Nazıroğlu

    Present address: Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Qatar Foundation, Doha, Qatar

Authors and Affiliations

  1. Neuroscience Research Center, Süleyman Demirel University, Isparta, Turkey

    Mustafa Nazıroğlu

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

    Mustafa Nazıroğlu, Bilal Çiğ & Mehmet Aykur

  3. Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey

    Mehmet Şahin & Yunus Ugan

  4. Department of Dermatology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey

    İjlal Erturan

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  1. Mustafa Nazıroğlu
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Correspondence to Mustafa Nazıroğlu.

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Nazıroğlu, M., Şahin, M., Çiğ, B. et al. Hypericum perforatum Modulates Apoptosis and Calcium Mobilization Through Voltage-Gated and TRPM2 Calcium Channels in Neutrophil of Patients with Behcet’s Disease. J Membrane Biol 247, 253–262 (2014). https://doi.org/10.1007/s00232-014-9630-7

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