Browsing by Author "Cinar, Ramazan"

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Curcumin Protects Against Mpp+-Induced Neurotoxicity in Sh-Sy5y Cells by Modulating the Trpv4 Channel
(Springer, 2025) Cinar, Ramazan; Yildizhan, Kenan
BackgroundIt is well acknowledged that neuroinflammation, mitochondrial dysfunction, and oxidative stress (OS) play a role in the etiology of Parkinson's disease (PD). Curcumin (CUR) protect neuronal cells by interfering with the production of reactive oxygen species (ROS) in neuronal cells and suppressing OS. In this study, we investigated the role of the TRPV4 channel under CUR stimulation in the PD model induced by MPP+ in SH-SY5Y cells. MethodsThe cells were divided into four groups: control, CUR, MPP+ and MPP++CUR. In addition, incubations were performed with TRPV4 channel agonist GSK1016790A (GSK) and its antagonist Ruthenium red (Rr) to follow the Ca2+ current induced through the TRPV4 channel. ResultsMPP+ exposure increased mitochondrial and intracellular ROS production and mitochondrial membrane potential in the cell, while decreasing GSH levels. During CUR and Rr incubation, MPP+ exposure and TRPV4 agonist GSK-induced TRPV4 overstimulation were down-regulated. The effects of MPP+ on intracellular damage were changed by CUR treatment, as seen in changes in GSH levels, mROS, iROS, JC/1, apoptosis, and TRPV4 expression value compared to the MPP+ group. ConclusionsThe CUR treatment in the in vitro PD model created with MPP+ reduced cellular damage by regulating mitochondrial dysfunction, OS and TRPV4 channel activation in MPP+-induced neurotoxicity with the antioxidant properties of CUR.
The Involvement of Trpm2 on the Mpp+-Induced Oxidative Neurotoxicity and Apoptosis in Hippocampal Neurons From Neonatal Mice: Protective Role of Resveratrol
(Taylor & Francis Ltd, 2022) Yildizhan, Kenan; Cinar, Ramazan; Naziroglu, Mustafa
Parkinson's disease (PD) is an age-related chronic neurodegenerative disease. Although PD is known to be a result of damage to hippocampal neurons, its molecular mechanism has yet to be completely clarified. The neurodegeneration in hippocampal neurons has been suggested to include excessive production of reactive oxygen species (ROS). Mitochondrial dysfunction and disruption of intracellular Ca2+ homeostasis play the most important role in the increase in ROS production for the cells. Remarkably, it is stated in the literature that especially the change of Ca2+ homeostasis triggers neuronal degeneration. TRPM2 is a unique calcium-permeable nonselective cation channel, and densest in the numberless neuronal population. The current study aims to elucidate the effect of antioxidant resveratrol (Resv) on TRPM2-mediated oxidative stress (OS) induced by 1-methyl-4-phenylpyridinium (MPP) exposure in the primary mouse hippocampal neurons. The neurons were divided into four groups as Control, Resv , MPP, and MPP+ Resv. In the current results, the activation of TRPM2 was observed in primary hippocampal neurons with MPP incubation. TRPM2 channel expression levels in the MPP group increased in hippocampal neurons after MPP exposure. In addition, intracellular free Ca2+ concentration and TRPM2 channel currents were highest in MPP groups, although they were decreased by the Resv treatment. In addition, mitochondrial membrane depolarization, ROS, caspase-3, caspase-9, and apoptosis values induced by MPP decreased with resveratrol treatment. In conclusion, in our study, we observed that the dysregulation of OS-induced TRPM2 channel activation in hippocampal neurons exposed to MPP caused apoptotic cell death in neurons, while the use of resveratrol had a protective effect by reducing OS resources in the environment.
Protective Role of Zingerone Against High Glucose-Induced Retinal Pigment Epithelial Cell Damage Through Modulation of the Trpm2 Channel Pathway
(Springer, 2026) Cig, Esmanur; Yardimci, Mahmut; Cinar, Ramazan; Yildizhan, Kenan
Background Diabetic retinopathy (DRP) is a leading cause of vision loss associated with chronic hyperglycemia-induced oxidative stress (OS), inflammation, and mitochondrial dysfunction in retinal pigment epithelium (RPE) cells. Zingerone (ZGN), a phenolic compound derived from Zingiber officinale, exhibits potent antioxidant and anti-inflammatory properties; however, its molecular targets in diabetic retinal damage remain unclear.MethodsThis study investigated the protective effects of ZGN against high glucose (HG)-induced cytotoxicity in human ARPE-19 cells, focusing on the ROS/PARP-1/TRPM2 signaling pathway. The cells were exposed to HG (30 mM) and treated with ZGN (0-80 mu M) for 24 h.ResultsHG incubation significantly increased MDA, PARP-1, ROS, intracellular calcium ion ([Ca-2(+)]i), and pro-inflammatory cytokines (IL-1 beta and TNF-alpha) in ARPE-19 cells, while decreasing GSH levels and cell viability. ZGN significantly restored OS, reduced cytokine release, [Ca-2(+)]i, and preserved mitochondrial membrane potential. Western blot and fluorescence analyses showed that ZGN reduced TRPM2 protein expression and suppressed [Ca-2(+)]i overload. Moreover, pharmacological inhibition of TRPM2 with 2-APB and of PARP-1 with DPQ enhanced the cytoprotective effects of ZGN, confirming that the ROS/PARP-1/TRPM2 axis mediates HG-induced oxidative damage.ConclusionsThese findings suggest that ZGN protects ARPE-19 cells by integrating OS with [Ca-2(+)]i homeostasis, providing a mechanistic rationale for its potential therapeutic use in preventing OS-related retinal damage in DRP.Graphical AbstractHigh glucose (HG) exposure triggers excessive production of reactive oxygen species (ROS) in retinal pigment epithelial (ARPE-19) cells, leading to oxidative stress (OS), inflammation, mitochondrial depolarisation, and subsequent cell death. The overproduction of ROS activates poly (ADP-ribose) polymerase-1 (PARP-1), generating ADP-ribose (ADPR) and thereby stimulating the TRPM2 channel to promote Ca-2(+) influx. Elevated intracellular Ca-2(+) further disrupts mitochondrial homeostasis, amplifies ROS accumulation, and initiates apoptotic signaling cascades. Consequently, OS depletes cellular antioxidant defences (GSH) while increasing lipid peroxidation (MDA) and pro-inflammatory cytokines (IL-1 beta and TNF-alpha). ZGN interrupts this vicious cycle through its potent antioxidant and anti-inflammatory actions, enhancing GSH levels, scavenging ROS, suppressing MDA, IL-1 beta, and TNF-alpha production, and preventing TRPM2-mediated Ca-2(+) overload. By restoring OS, reducing inflammatory mediators, and preserving mitochondrial integrity, ZGN effectively prevents HG-induced apoptosis and cell death, underscoring its therapeutic potential against OS-associated retinal injury.
Protective Role of Zingerone Against High Glucose-Induced Retinal Pigment Epithelial Cell Damage Through Modulation of the TRPM2 Channel Pathway (Vol 53, 309, 2026)
(Springer, 2026) Cig, Esmanur; Yardimci, Mahmut; Cinar, Ramazan; Yildizhan, Kenan
The Role of Trpm2 Channel in Doxorubicin-Induced Cell Damage in Laryngeal Squamous Cancer Cells
(Maik Nauka/interperiodica/springer, 2025) Yagci, Tarik; Cinar, Ramazan; Altiner, Halil Ibrahim; Duendar, Riza; Yildizhan, Kenan
Laryngeal squamous cell carcinoma is a common type of head and neck cancer. This study investigated the role of the TRPM2 channel in doxorubicin (DOX)-induced cell damage in human laryngeal squamous cancer cells (Hep-2). Cells were exposed to various DOX concentrations and the appropriate dose was found. Then, TRPM2 antagonist ACA was treated. At the end of the study, cell viability test, Western blot and oxidative stress and inflammatory markers were examined. The results showed that TRPM2 channel expression increased with DOX administration, and DOX incubation in cells caused an increase in ROS, MDA, IL-1 beta, IL-6, and TNF-alpha levels, while GSH and GSH-Px levels decreased. Concurrent treatment with ACA attenuated these effects and reduced oxidative stress and inflammation. In addition, DOX-induced apoptosis markers including Casp-3, Casp-8, Casp-9, p53, and Bax were elevated, while Bcl-2 levels were decreased; ACA treatment reversed these changes. The study demonstrated that DOX treatment significantly enhances TRPM2 channel activation and ROS production in Hep-2 cells, thereby initiating apoptotic pathways that lead to cell death. Consequently, targeting the TRPM2 channel may represent a promising therapeutic strategy for treating laryngeal cancer.