Glibenclamide Decreases ATP-Induced Intracellular Calcium Transient Elevation via Inhibiting Reactive Oxygen Species and Mitochondrial Activity in Macrophages

Li, Duoling; Ma, Zhiyong; Fu, Zhijie; Ling, Mingying; Yan, Chuanzhu; Zhang, Yun

doi:10.1371/journal.pone.0089083

Cited by 16 publications

(15 citation statements)

References 31 publications

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“…We also demonstrate that glibenclamide in the concentration of 100 µM does not affect the intracellular Ca 2+ trend in mouse oocytes. Our results are in agreement with Li et al study, which showed that glibenclamide did not affect the resting Ca 2+ of Raw 264.7 macrophages (15). This observation could be explained as glibenclamide might speci cally target mitochondrial K ATP channels, not the plasmalemmal ones.…”

Section: Discussionsupporting

confidence: 93%

Assessment of Intracellular Calcium and Plasmalemmal Membrane Potential in Cryopreserved Metaphase II Mouse Oocytes

Ammar¹,

Moodley

2020

Preprint

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Objectives: Ca2+ is critical for normal oocyte activation and fertilization, and any alteration to the Ca2+ homeostasis may lead to failed fertilization or even cell death. It has been shown that intracellular Ca2+ is increased in bovine and human oocytes when cultured in vitro. Additionally, ATP sensitive potassium channels have been characterised recently in human and Xenopus oocytes Glibenclamide a KATP channel blocker was shown to protect human oocytes from Ca+2 overloading. None of these studies have been conducted in mouse oocytes to determine if they are a suitable alternative to human oocytes in the research setting. Thus, this research note aims to demonstrate if cryopreserved metaphase II (MII) mouse oocytes show similar Ca+2 and plasmalemmal membrane potential dynamics to those in human oocytes. Also, to show if glibenclamide influences Ca+2, and plasmalemmal membrane potential in cryopreserved metaphase II mouse oocytes. Results: our data did not show an increase in intracellular Ca2+ in untreated cryopreserved mouse oocytes loaded with Fluo-3 AM dye. However, an increase in the plasmalemmal membrane potential was noticed (hyperpolarization). Glibenclamide has shown no significant effect on Ca+2, mitochondrial and plasmalemmal membrane potential.

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Section: Discussionsupporting

confidence: 93%

Assessment of Intracellular Calcium and Plasmalemmal Membrane Potential in Cryopreserved Metaphase II Mouse Oocytes

Ammar¹,

Moodley

2020

Preprint

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“…A recent work [ 60 ] demonstrated that GLI, used in the present work for comparison to PTX, decreased intracellular ROS and mitochondrial activity in macrophages. Glibenclamide or glyburide, is an antidiabetic second generation sulfonylurea was shown to present a potent anti-inflammatory effect, as demonstrated by decreases in pro-inflammatory cytokines and nitrite in paws and sera from diabetic rats.…”

Section: Discussionmentioning

confidence: 62%

Pentoxifylline reduces the inflammatory process in diabetic rats: relationship with decreases of pro-inflammatory cytokines and inducible nitric oxide synthase

et al. 2015

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Studies suggest that inflammation is a key factor in the pathogenesis of diabetes mellitus. Pro-inflammatory cytokines, such as IL-6 and TNF-alpha, are produced by adipose tissue in large quantities, in obese and especially in diabetic individuals. Pentoxifylline (PTX) is a non-selective phosphodiesterase inhibitor with anti-inflammatory and antioxidant actions that may contribute to alleviate diabetes side effects, as neuropathy, retinopathy and nephropathy. This study aims to investigate PTX anti-inflammatory effects on the carrageenan-induced paw edema model, in alloxan-induced diabetic rats. Diabetic animals (male Wistar rats, 200–250 g) were daily treated with PTX (25, 50, 100 mg/kg, p.o.), glibenclamide (GLI, 5 mg/kg, p.o., as reference) or water, for 5 days. Afterwards, carrageenan-treated paws were dissected, their skin removed and the tissue used for preparation of homogenates and measurements of IL-6 and TNF-alpha by Elisa. Serum levels of nitrite were also determined and paw slices used for iNOS immunohistochemistry assays. We showed that diabetic rats presented an amplification of the inflammatory response, as related to non-diabetic rats, what was evident 48 h after the edema-induction. The PTX-treatment of diabetic rats reduced glycemia (as related to untreated-diabetic ones) and the paw edema. It also brought edema volumes to values similar to those of non-diabetic rats, at the same observation time. The increased TNF-alpha and IL-6 levels in paws of untreated-diabetic rats were reduced in diabetic animals after PTX treatments. Besides, the increased levels of nitrite in the serum of diabetic rats were also decreased by PTX. Furthermore, a higher number of iNOS immunostained cells was demonstrated in paw tissues from untreated-diabetic rats, as related to those of PTX-treated diabetic animals. Our results show that PTX reduces inflammatory parameters, as pro-inflammatory cytokines and iNOS expression, indicating the potential benefit of the drug for the treatment of diabetes and related pathologic conditions.

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“…HT22[mtAEQ] cells were further treated with glibenclamide ( Figure 6f), an inhibitor of the ATP-dependent potassium channel (K ATP ), 41,42 which was previously shown to reduce ATP-induced [Ca 2+ ] m uptake. 43 However, in response to carbachol (Supplementary Figure S6F), glibenclamide did not reduce the [Ca 2+ ] m peak amplitude. Notably, glibenclamide treatment rendered no protection against glutamate-induced cell death (Supplementary Figure S6E), and did not attenuate CyPPAmediated protection against glutamate toxicity in HT22 cells.…”

Section: Resultsmentioning

confidence: 90%

SK2 channels regulate mitochondrial respiration and mitochondrial Ca2+ uptake

et al. 2017

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Mitochondrial calcium ([Ca]) overload and changes in mitochondrial metabolism are key players in neuronal death. Small conductance calcium-activated potassium (SK) channels provide protection in different paradigms of neuronal cell death. Recently, SK channels were identified at the inner mitochondrial membrane, however, their particular role in the observed neuroprotection remains unclear. Here, we show a potential neuroprotective mechanism that involves attenuation of [Ca] uptake upon SK channel activation as detected by time lapse mitochondrial Ca measurements with the Ca-binding mitochondria-targeted aequorin and FRET-based [Ca] probes. High-resolution respirometry revealed a reduction in mitochondrial respiration and complex I activity upon pharmacological activation and overexpression of mitochondrial SK2 channels resulting in reduced mitochondrial ROS formation. Overexpression of mitochondria-targeted SK2 channels enhanced mitochondrial resilience against neuronal death, and this effect was inhibited by overexpression of a mitochondria-targeted dominant-negative SK2 channel. These findings suggest that SK channels provide neuroprotection by reducing [Ca] uptake and mitochondrial respiration in conditions, where sustained mitochondrial damage determines progressive neuronal death.

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Glibenclamide Decreases ATP-Induced Intracellular Calcium Transient Elevation via Inhibiting Reactive Oxygen Species and Mitochondrial Activity in Macrophages

Cited by 16 publications

References 31 publications

Assessment of Intracellular Calcium and Plasmalemmal Membrane Potential in Cryopreserved Metaphase II Mouse Oocytes

Assessment of Intracellular Calcium and Plasmalemmal Membrane Potential in Cryopreserved Metaphase II Mouse Oocytes

Pentoxifylline reduces the inflammatory process in diabetic rats: relationship with decreases of pro-inflammatory cytokines and inducible nitric oxide synthase

SK2 channels regulate mitochondrial respiration and mitochondrial Ca2+ uptake

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