Inhibition of γ-secretase activity reduces Aβ production, reduces oxidative stress, increases mitochondrial activity and leads to reduced vulnerability to apoptosis: Implications for the treatment of Alzheimer's disease

Sheng, Baiyang; Gong, Kai; Niu, Ying; Liu, Lingling; Yan, Yishu; Lu, Guangyuan; Zhang, Lihai; Hu, Min; Zhao, Nanming; Zhang, Xiufang; Tang, Peifu; Gong, Yandao

doi:10.1016/j.freeradbiomed.2009.02.018

Cited by 90 publications

(62 citation statements)

References 70 publications

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“…Data were analyzed by independent sample t tests and p < 0.05 was considered statistically significant [17,18].…”

Section: Methodsmentioning

confidence: 99%

The expression and localization of neuregulin-1 (Nrg1) in the gastrointestinal system of the rhesus monkey

Zhao

2013

Folia Histochem Cytobiol.

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Although Neuregulin-1 (Nrg1) and its cognate receptors have been found at the mRNA level in human gastrointestinal (GI) tract and their functional roles have been evaluated in vitro, their morphological distribution in higher mammals are not fully elucidated. The present research focused on morphological distribution of Nrg1 and its receptors, ErbB2 and ErbB4, in main GI tissues of the non-human primate rhesus monkey. The morphological expression of Nrg1 and its ErbB2 and ErbB4 receptors as well as their potential colocalization were determined by double immunofluorescence staining in esophagus, stomach, small intestine and colon tissues derived from the rhesus monkey tissue microarray. The Nrg1 level on each sample was indexed by the fold of integrated fluorescence intensity (IFI) relative to that of one brain cortical tissue from the rhesus monkey. Differential expression of Nrg1 and its receptors ErbB2 and ErbB4 was found in the GI structures, with higher expression levels detected in stomach and small intestine. Co-localization of Nrg1 with ErbB2 and/or ErbB4 receptors was most apparently detected in the stomach, followed by small intestine, colon, and esophagus. This investigation morphologically profiles the differential expression of Nrg1 and its receptors in main GI structures, suggesting an autocrine or paracrine loop-directed Nrg1/ErbB receptor signaling pathway in these organs of higher mammals.

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“…Data were analyzed by independent sample t tests and p < 0.05 was considered statistically significant [17,18].…”

Section: Methodsmentioning

confidence: 99%

The expression and localization of neuregulin-1 (Nrg1) in the gastrointestinal system of the rhesus monkey

Zhao

2013

Folia Histochem Cytobiol.

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“…ROS levels in the erythrocytes were determined by measuring the oxidative conversion of 2′,7′-dichlorofluorescin diacetate (DCFH-DA) to fluorescent compound DCF using a detection kit (Beyotime, Nantong, China) as described previously [48][49][50]. DCF fluorescence in the erythrocytes was determined at 485 nm excitation and 520 nm emission using a fluorescence spectrophotometer (Thermo, Waltham, USA).…”

Section: Measurement Of Rosmentioning

confidence: 99%

“…All statistical analyses were performed using the SPSS 13.0 for Window software (SPSS, Chicago, IL, USA) [66]. 50 ) on the activities of caspase-8, caspase-9 and caspase-3 were respectively estimated to be 0.60, 0.61 and 0.35 mM that are the minimum values among amino acids examined so far (see Table 1 in Ref. [45]).…”

Section: Protein Measurements and Statistical Analysismentioning

confidence: 99%

The metabolites of glutamine prevent hydroxyl radical-induced apoptosis through inhibiting mitochondria and calcium ion involved pathways in fish erythrocytes

Jiang

Liu

et al. 2016

Free Radical Biology and Medicine

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a b s t r a c tThe present study explored the apoptosis pathways in hydroxyl radicals ( • OH)-induced carp erythrocytes. Carp erythrocytes were treated with the caspase inhibitors in physiological carp saline (PCS) or Ca 2 þ -free PCS in the presence of 40 μM FeSO 4 /20 μM H 2 O 2 . The results showed that the generation of reactive oxygen species (ROS), the release of cytochrome c and DNA fragmentation were caspase-dependent, and Ca 2 þ was involved in calpain activation and phosphatidylserine (PS) exposure in • OH-induced carp erythrocytes. Moreover, the results suggested that caspases were involved in PS exposure, and Ca 2 þ was involved in DNA fragmentation in • OH-induced fish erythrocytes. These results demonstrated that there might be two apoptosis pathways in fish erythrocytes, one is the caspase and cytochrome c-dependent apoptosis that is similar to that in mammal nucleated cells, the other is the Ca 2 þ -involved apoptosis that was similar to that in mammal non-nucleated erythrocytes. So, fish erythrocytes may be used as a model for studying oxidative stress and apoptosis in mammal cells. Furthermore, the present study investigated the effects of glutamine (Gln)'s metabolites [alanine (Ala), citrulline (Cit), proline (Pro) and their combination (Ala 10 Pro 4 Cit 1 )] on the pathways of apoptosis in fish erythrocytes. The results displayed that Ala, Cit, Pro and Ala 10 Pro 4 Cit 1 effectively suppressed ROS generation, cytochrome c release, activation of caspase-3, caspase-8 and caspase-9 at the physiological concentrations, prevented Ca 2 þ influx, calpain activation, PS exposure, DNA fragmentation and the degradation of the cytoskeleton and oxidation of membrane and hemoglobin (Hb) and increased activity of anti-hydroxyl radical (AHR) in • OH-induced carp erythrocytes. Ala 10 Pro 4 Cit 1 produced a synergistic effect of inhibited oxidative stress and apoptosis in fish erythrocytes. These results demonstrated that Ala, Cit, Pro and their combination can protect mammal erythrocytes and nucleated cells against oxidative stress and apoptosis. The studies supported the use of Gln, Ala, Cit and Pro as oxidative stress and apoptosis inhibitors in mammal cells and the hypothesis that the inhibited effects of Gln on oxidative stress and apoptosis are at least partly dependent on that of its metabolites in mammalian.

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“…Sham control: normal lymphocytes Radiation control: γ-irradiated lymphocytes (3 Gy) Edaravone+γ-radiation: edaravone (100 μM) plus irradiated (3 Gy) lymphocytes Intracellular reactive oxygen species measurement Intracellular ROS was determined by 2′,7′-dichlorfluoresceindiacetate (DCFH-DA) as previously described (Sheng et al 2009). In a 24-well dish after irradiation, 2×10 5 cells from each group were seeded.…”

Section: Irradiation Proceduresmentioning

confidence: 99%

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage

Chen

Liu

Dong

et al. 2015

Cell Stress and Chaperones

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Radiation-induced cellular injury is attributed primarily to the harmful effects of free radicals, which play a key role in irradiation-induced apoptosis. In this study, we investigated the radioprotective efficacy of edaravone, a licensed clinical drug and a powerful free radical scavenger that has been tested against γ-irradiation-induced cellular damage in cultured human peripheral blood lymphocytes in studies of various diseases. Edaravone was pre-incubated with lymphocytes for 2 h prior to γ-irradiation. It was found that pretreatment with edaravone increased cell viability and inhibited generation of γ-radiation-induced reactive oxygen species (ROS) in lymphocytes exposed to 3 Gy γ-radiation. In addition, γ-radiation decreased antioxidant enzymatic activity, such as superoxide dismutase and glutathione peroxidase, as well as the level of reduced glutathione. Conversely, treatment with 100 μM edaravone prior to irradiation improved antioxidant enzyme activity and increased reduced glutathione levels in irradiated lymphocytes. Importantly, we also report that edaravone reduced γ-irradiation-induced apoptosis through downregulation of Bax, upregulation of Bcl-2, and consequent reduction of the Bax:Bcl-2 ratio. The current study shows edaravone to be an effective radioprotector against γ-irradiation-induced cellular damage in lymphocytes in vitro. Finally, edaravone pretreatment significantly reduced DNA damage in γ-irradiated lymphocytes, as measured by comet assay (% tail DNA, tail length, tail moment, and olive tail moment) (p<0.05). Thus, the current study indicates that edaravone offers protection from radiation-induced cytogenetic alterations.

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Inhibition of γ-secretase activity reduces Aβ production, reduces oxidative stress, increases mitochondrial activity and leads to reduced vulnerability to apoptosis: Implications for the treatment of Alzheimer's disease

Cited by 90 publications

References 70 publications

The expression and localization of neuregulin-1 (Nrg1) in the gastrointestinal system of the rhesus monkey

The expression and localization of neuregulin-1 (Nrg1) in the gastrointestinal system of the rhesus monkey

The metabolites of glutamine prevent hydroxyl radical-induced apoptosis through inhibiting mitochondria and calcium ion involved pathways in fish erythrocytes

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage

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