Apoptosis Regulation at the Mitochondrial Outer Membrane

Gillies, Laura A.; Kuwana, Tomomi

doi:10.1002/jcb.24709

Cited by 184 publications

(134 citation statements)

References 108 publications

(127 reference statements)

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“…The balance between Bcl-2 and Bax is critical in the activation of terminal caspases such as caspase-9 and caspase-3 [19]. Treatment of PC12 cells with OGD/R significantly decreased protein levels of Bcl-2 and increased protein levels of Bax compared with the control group, which resulted in a low ratio of Bcl-2/ Bax (P < 0.05 vs. control) (Fig.…”

Section: Resveratrol Inhibited Ogd/r-induced Cytochrome C Release Fromentioning

confidence: 89%

Resveratrol protects PC12 cells against OGD/R-induced apoptosis via the mitochondrial-mediated signaling pathway

Liu

Zhu

Chen

et al. 2016

ABBS

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In this study, we investigated the neuroprotective potential of resveratrol against oxygen glucose deprivation/reoxygenation (OGD/R)-induced apoptotic damages in well-differentiated PC12 cells and the underlying mechanisms. Cells were incubated under normal condition or OGD/R in the presence or absence of 10 μM resveratrol. Cell viability was determined with methyl-thiazolyl-tetrazolium (MTT) assay. Apoptotic ratio was determined with Hoechst 33342 staining and Annexin V-FITC/PI double staining. Oxidative stress was evaluated by measuring the intracellular reactive oxygen species (ROS), the mitochondrial superoxide, the malondialdehyde (MDA) content, and the activities of superoxide dismutase (SOD) and catalase (CAT). The intracellular calcium ([Ca 2+ ]i) was estimated by Fluo-3/ AM. The mitochondrial membrane potential (MMP) was evaluated by 5,5′,6,6′-tetrachloro-1,1,3,3′-tetraethyl-benzimidazolyl-carbocyanine iodide (JC-1) and rhodamine 123 (Rh123). The opening of mitochondrial permeability transition pore (MPTP) was determined by the Calcein/Co 2+ -quenching technique. The protein levels of cytochrome c, Bcl-2, Bax, cleaved caspase-9, and cleaved caspase-3 were detected by western blot analysis. The results showed that 10 μM resveratrol attenuated OGD/R-induced cell viability loss and cell apoptosis, which was associated with the decreases in the MDA content and the increases in the SOD and CAT activities. Furthermore, the accumulation of intracellular ROS and mitochondrial superoxide, disturbance of [Ca 2+ ]i homeostasis, reduction of MMP, opening of MPTP, and release of mitochondrial cytochrome c observed in OGD/R-injured cells, which indicated a switch on the mitochondrial-mediated apoptotic pathway, were all reversed by resveratrol. These results suggest that resveratrol administration may play a neuroprotective role via modulating the mitochondrial-mediated signaling pathway in OGD/R-induced PC12 cell injury.

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Section: Resveratrol Inhibited Ogd/r-induced Cytochrome C Release Fromentioning

confidence: 89%

Resveratrol protects PC12 cells against OGD/R-induced apoptosis via the mitochondrial-mediated signaling pathway

Liu

Zhu

Chen

et al. 2016

ABBS

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“…Therefore, mitochondria are important therapeutic targets for ischemic cerebral stroke (Chan, 2005). Among numerous mitochondrial proteins, Bcl-2 family including Bcl-2, Bcl-XL, Mcl-1, Bax, Bak, Bcl-XS, Bad, Bik and Bid are central regulators of mitochondria-dependent programmed cell death (Graham et al, 2000;Antonsson, 2001;Youle and Strasser, 2008;Gillies and Kuwana, 2014). Bcl-2 is an integral membrane protein located mainly on the outer membrane of mitochondria.…”

Section: Discussionmentioning

confidence: 99%

Protosappanin B protects PC12 cells against oxygen–glucose deprivation-induced neuronal death by maintaining mitochondrial homeostasis via induction of ubiquitin-dependent p53 protein degradation

Zeng

Liao

Zhao

et al. 2015

European Journal of Pharmacology

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“…In the present study, increases in the mRNA levels of Bcl-2 and Hspa4 were identified in hippocampal NSCs following treatment with 20 µM selegiline for 48 h. The Bcl-2 protein family controls the release of cytochrome c (Cyt-c) from the mitochondria and consists of pro-apoptotic (Bcl-2-associated X protein, Bcl-2 homologous antagonist/killer, BH3 interacting-domain death agonist, Bcl-2-associated death promoter) and anti-apoptotic [Bcl-2, Bcl-extra large (Bcl-xL)] members (34). The primary function of anti-apoptotic Bcl-2 is to suppress mitochondrial Cyt-c release, by regulating physiological membrane permeability, Ca 2+ release and oxidative stress in the mitochondria (35,36).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of selegiline on rat neural stem cells treated with hydrogen peroxide

et al. 2017

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Abstract. Oxidative stress and reactive oxygen species generation have been implicated in the pathogenesis of several neurological disorders including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis and multiple sclerosis. In the present study, the neuroprotective effects of selegiline against hydrogen peroxide-induced oxidative stress in hippocampus-derived neural stem cells (NSCs) were evaluated. NSCs isolated from neonatal Wistar rats were pretreated with different doses of selegiline for 48 h and then exposed to 125 µM H 2 O 2 for 30 min. Using MTT and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays, acridine orange/ethidium bromide staining and reverse transcription-quantitative polymerase chain reaction, the effects of selegiline on cell survival, apoptosis and the expression of B-cell lymphoma 2 (Bcl-2) and heat shock protein 4 (Hspa4) in pretreated stem cells were assessed compared with a control group lacking pretreatment. The results indicated that the viability of cells pretreated with 20 µM selegiline was significantly increased compared with the control group (P<0.05). Additionally, 20 µM selegiline increased the mRNA expression of Bcl-2 and Hspa4 (P<0.05 vs. control) and suppressed oxidative stress-induced cell death (apoptosis and necrosis; P<0.05 vs. control and 10 µM groups). From these findings, it was concluded that selegiline may be a therapeutic candidate for the treatment of neurological diseases mediated by oxidative stress. IntroductionThe most common neorodegenerative disorders, namely Alzheimer's disease (AD) and Parkinson's disease (PD), are prevalent in ~1% of individuals aged 60 years and older (1). Their etiologies remain uncertain, though there are a number of established pathogenic factors, including oxidative stress, neural apoptosis, mitochondrial dysfunction, excitotoxicity, impairment of the ubiquitin-proteasome system and inflammation (2,3). Neuroprotective therapy has been suggested to prevent disease progression by inhibiting the action of pathogenic factors, for instance, by reducing the production of reactive oxygen species (ROS) (4). Overproduction of ROS may cause oxidative damage to biomolecules and subsequently DNA damage, ultimately leading to the development of neurodegenerative diseases. According to studies on PD, inhibitors of type B monoamine oxidase (MAO), including selegiline [also known as (-)-deprenyl] and rasagiline, are among the most promising neuroprotective agents identified to date (5-7). MAO exists in two forms, MAO-A and -B. The catalytic activity of these enzymes generates H 2 O 2 and nitrogen species, which are toxic products that may cause oxidative damage to mitochondrial DNA (mtDNA) and thus have potential implications for apoptosis, aging and neurodegenerative processes (8). The MAO-B inhibitor, selegiline, is typically recommended as a first-line treatment for PD and has been demonstrated to possess neuroprotective functions (9); notably, this inhibitor protected neuronal cells against induc...

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Apoptosis Regulation at the Mitochondrial Outer Membrane

Cited by 184 publications

References 108 publications

Resveratrol protects PC12 cells against OGD/R-induced apoptosis via the mitochondrial-mediated signaling pathway

Resveratrol protects PC12 cells against OGD/R-induced apoptosis via the mitochondrial-mediated signaling pathway

Protosappanin B protects PC12 cells against oxygen–glucose deprivation-induced neuronal death by maintaining mitochondrial homeostasis via induction of ubiquitin-dependent p53 protein degradation

Neuroprotective effects of selegiline on rat neural stem cells treated with hydrogen peroxide

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