Exposure to a 50-Hz magnetic field induced mitochondrial permeability transition through the ROS/GSK-3β signaling pathway

2016 ◽  
Vol 92 (3) ◽  
pp. 148-155 ◽  
Author(s):  
Baihuan Feng ◽  
Liping Qiu ◽  
Chunmei Ye ◽  
Liangjing Chen ◽  
Yiti Fu ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Signaling Pathway ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Mitochondrial Permeability ◽  
Gsk 3Β

Abstract 168: Resveratrol Translocates Gsk-3β To Mitochondria And Protects The Heart At Reperfusion By Targeting The Mitochondrial Permeability Transition Pore

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Jinkun Xi ◽  
Huihua Wang ◽  
Guillaume Chanoit ◽  
Guang Cheng ◽  
Robert A Mueller ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Cyclophilin D ◽  
Risk Zone ◽  
Mitochondrial Permeability ◽  
Mptp Opening ◽  
Gsk 3Β

Although resveratrol has been demonstrated to be cardioprotective, the detailed cellular and molecular mechanisms that mediate the protection remain elusive. We aimed to determine if resveratrol protects the heart at reperfusion by modulating the mitochondrial permeability transition pore (mPTP) opening through glycogen synthase kinase 3β (GSK-3β). Resveratrol (10μM) given at reperfusion reduced infarct size (12.2 ± 2.5 % of risk zone vs. 37.9 ± 3.1 % of risk zone in control, n = 6) in isolated rat hearts subjected to 30 min regional ischemia followed by 2 h of reperfusion, an effect that was abrogated by the mPTP opener atractyloside (30.9 ± 8.1 % of risk zone), implying that resveratrol may protect the heart at reperfusion by modulating the mPTP opening. To define the signaling mechanism underlying the action of resveratrol, we determined GSK-3β activity by measuring its phosphorylation at Ser 9 . Resveratrol significantly enhanced GSK-3β phosphorylation upon reperfusion (225.2 ± 30.0 % of control at 5 min of reperfusion). Further experiments showed that resveratrol induces translocation of GSK-3β to mitochondria and translocated GSK-3β interacts with the mPTP component cyclophilin D but not VDAC (the voltage-dependent anion channel) or ANT (the adenine nucleotide translocator) in cardiac mitochondria. Taken together, these data suggest that resveratrol prevents myocardial reperfusion injury by targeting the mPTP opening via GSK-3β. Translocation of GSK-3β to mitochondria and its interaction with the mPTP component cyclophilin D may serve as an essential mechanism that mediates the protective effect of resveratrol on reperfusion injury.

Cardioprotection of the aged rat heart by GSK-3β inhibitor is attenuated: age-related changes in mitochondrial permeability transition pore modulation

2011 ◽  
Vol 300 (3) ◽  
pp. H922-H930 ◽  
Author(s):  
Jiang Zhu ◽  
Mario J. Rebecchi ◽  
Peter S. A. Glass ◽  
Peter R. Brink ◽  
Lixin Liu
Keyword(s):  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Male Rats ◽  
Mitochondrial Permeability ◽  
Mptp Opening ◽  
Gsk 3Β

It is well established that inhibition of glycogen synthase kinase (GSK)-3β in the young adult myocardium protects against ischemia-reperfusion (I/R) injury through inhibition of mitochondrial permeability transition pore (mPTP) opening. Here, we investigated age-associated differences in the ability of GSK-3β inhibitor [SB-216763 (SB)] to protect the heart and to modulate mPTP opening during I/R injury. Fischer 344 male rats were assigned from their respective young or old age groups. Animals were subjected to 30 min ischemia following 120 min reperfusion to determine myocardial infarction (MI) size in vivo. Ischemic tissues were collected 10 min after reperfusion for nicotinamide adenine dinucleotide (NAD+) measurements and immunoblotting. In parallel experiments, ventricular myocytes isolated from young or old rats were exposed to oxidative stress through generation of reactive oxygen species (ROS), and mPTP opening times were measured by using confocal microscopy. Our results showed that SB decreased MI in young SB-treated rats compared with young untreated I/R animals, whereas SB failed to significantly affect MI in the old animals. SB also significantly increased GSK-3β phosphorylation in young rats, but phosphorylation levels were already highly elevated in old control groups. There were no significant differences observed between SB-treated and untreated old animals. NAD+levels were better maintained in young SB-treated animals compared with the young untreated group during I/R, but this relative improvement was not observed in old animals. SB also significantly prolonged the time to mPTP opening induced by ROS in young cardiomyocytes, but not in aged cardiomyocytes. These results demonstrate that this GSK-3β inhibitor fails to protect the aged myocardium in response to I/R injury or prevent mPTP opening following a rise in ROS and suggest that healthy aging alters mPTP regulation by GSK-3β.

Morphine prevents the mitochondrial permeability transition pore opening through NO/cGMP/PKG/Zn2+/GSK-3β signal pathway in cardiomyocytes

2010 ◽  
Vol 298 (2) ◽  
pp. H601-H607 ◽  
Author(s):  
Jinkun Xi ◽  
Wei Tian ◽  
Lei Zhang ◽  
Yulan Jin ◽  
Zhelong Xu
Keyword(s):  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Glycogen Synthase ◽  
Specific Inhibitor ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Mitochondrial Permeability ◽  
Mptp Opening ◽  
Pore Opening ◽  
Gsk 3Β

The aim of this study was to test whether morphine prevents the mitochondrial permeability transition pore (mPTP) opening through Zn2+ and glycogen synthase kinase 3β (GSK-3β). Fluorescence dyes including Newport Green Dichlorofluorescein (DCF), 4-amino-5-methylamino-2′,7′-difluorofluorescein (DAF-FM), and tetramethylrhodamine ethyl ester (TMRE) were used to image free Zn2+, nitric oxide (NO), and mitochondrial membrane potential (ΔΨm), respectively. Fluorescence images were obtained with confocal microscopy. Cardiomyocytes treated with morphine for 10 min showed a significant increase in Newport Green DCF fluorescence intensity, an effect that was reversed by the NO synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME), indicating that morphine mobilizes Zn2+ via NO. Morphine rapidly produced NO. ODQ and NS2028, the inhibitors of guanylyl cyclase, prevented Zn2+ release by morphine, implying that cGMP is involved in the action of morphine. The effect of morphine on Zn2+ release was also abolished by KT5823, a specific inhibitor of protein kinase G (PKG). Morphine prevented oxidant-induced loss of ΔΨm, indicating that morphine can modulate the mPTP opening. The effect of morphine on the mPTP was reversed by KT5823 and the Zn2+ chelator N, N, N′, N′-tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN). The action of morphine on the mPTP was lost in cells transfected with the constitutively active GSK-3β mutant, suggesting that morphine may prevent the mPTP opening by inactivating GSK-3β. In support, morphine significantly enhanced phosphorylation of GSK-3β at Ser9, and this was blocked by TPEN. GSK-3β small interfering RNA prevented the pore opening in the control cardiomyocytes but failed to enhance the effect of morphine on the mPTP opening. In conclusion, morphine mobilizes intracellular Zn2+ through the NO/cGMP/PKG signaling pathway and prevents the mPTP opening by inactivating GSK-3β through Zn2+.

scholarly journals Mitochondrial ROS Release and Subsequent Akt Activation Potentially Mediated the Anti-Apoptotic Effect of a 50-Hz Magnetic Field on FL Cells

2016 ◽  
Vol 38 (6) ◽  
pp. 2489-2499 ◽  
Author(s):  
Baihuan Feng ◽  
Chunmei Ye ◽  
Liping Qiu ◽  
Liangjing Chen ◽  
Yiti Fu ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Akt Activation ◽  
Mitochondrial Permeability ◽  
Mitochondrial Ros ◽  
Phosphorylated Akt ◽  
Early Apoptosis ◽  
Apoptotic Effect ◽  
Permeability Transition Pores

Background/Aims: Our previous study showed that exposure to a 50-Hz magnetic field (MF) could induce transient mitochondrial permeability transition (MPT) in cells. In the present study, the aim was to explore the possible biological implications of MF-induced transient MPT. Materials and Methods: Human amniotic (FL) cells were exposed to MF for different durations or intensities followed by incubation with staurosporine for 4 h. After MF exposure, cell early apoptosis, cell viability mitochondrial ROS and the level of phosphorylated Akt were assessed. After MF exposure followed by incubation with staurosporine, cell early apoptosis was assessed. Results: MF exposure had a protective effect against early apoptosis induced by staurosporine, which could be abolished by MPT inhibitors, although MF exposure alone had no significant effect on early apoptosis or viability of cells. In addition, exposing cells to MF increased the level of mitochondrial ROS which were released into cytoplasm through mitochondrial permeability transition pores (mPTP), and induced ROS-dependent phosphorylation of Akt. Furthermore, the anti-apoptotic effect of MF exposure was completely eliminated when Akt was inhibited. Conclusions: The present study indicated a possibility that mitochondrial ROS release through mPTP and subsequent Akt activation were necessary for the anti-apoptotic effect of MF.

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