NADPH oxidase 2-dependent oxidative stress, mitochondrial damage and apoptosis in the ventral cochlear nucleus of d-galactose-induced aging rats

Du, Zhongtao; Yang, Qianting; Liu, L.; Li, Shoudong; Zhao, Jing; Hu, Jiyi; Liu, C.; Qian, Daolin; Gao, Chengde

doi:10.1016/j.neuroscience.2014.11.061

Cited by 43 publications

(28 citation statements)

References 37 publications

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“…Therefore, in the present study, we applied D-gal-induced aging rat model to simulate aging-related damage of skeletal muscle. D-gal-treated rats showed typical aging symptoms, as evidenced by increased senescence-associated β-galactosidase and cell damage, which is consistent with previous demonstration that D-gal can cause the accumulation of reactive oxygen species (ROS) with a final oxidative stress [39]. Although the optimal dose and duration of D-gal administration are required to produce an aging rat model, the effect and toxicity of D-gal (150, 200 and 300 mg/kg) and SPD (1, 5 and 10 mg/kg) at various time durations have been systematically evaluated in our pilot experiments (data not shown).…”

Section: Discussionsupporting

confidence: 91%

Spermidine coupled with exercise rescues skeletal muscle atrophy from D-gal-induced aging rats through enhanced autophagy and reduced apoptosis via AMPK-FOXO3a signal pathway

et al. 2017

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The quality control of skeletal muscle is a continuous requirement throughout the lifetime, although its functions and quality present as a declining trend during aging process. Dysfunctional or deficient autophagy and excessive apoptosis may contribute to the atrophy of senescent skeletal muscle. Spermidine, as a natural polyamine, can be involved in important cellular functions for lifespan extension and stress resistance in several model organisms through activating autophagy. Similarly, cellular autophagic responses to exercise have also been extensively investigated. In the present study, in order to confirm the mitigation or amelioration of skeletal muscle atrophy in aging rats through spermidine coupled with exercise intervention and explore corresponding mechanisms, the rat model with aging-related atrophy of skeletal muscle was established by intraperitoneal injection of D-galactose (D-gal) (200 mg/kgd), and model rats were subjected to the intervention with spermidine (5 mg/kgd) or swimming (60 min/d, 5 d/wk) or combination for 42 days. Spermidine coupled with exercise could attenuate D-gal-induced aging-related atrophy of skeletal muscle through induced autophagy and reduced apoptosis with characteristics of more autophagosomes, activated mitophagy, enhanced mitochondrial quality, alleviated cell shrinkage, and less swollen mitochondria under transmission scanning microscopic observation. Meanwhile, spermidine coupled with exercise could induce autophagy through activating AMPK-FOXO3a signal pathway with characterization of increased Beclin1 and LC3-II/LC3-I ratio, up-regulated anti-apoptotic Bcl-2, down-regulated pro-apoptotic Bax and caspase-3, as well as activated AMPK and FOXO3a. Therefore, spermidine combined with exercise can execute the prevention or treatment of D-gal-induced aging-related skeletal muscle atrophy through enhanced autophagy and reduced apoptosis mediated by AMPK-FOXO3a signal pathway.

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Section: Discussionsupporting

confidence: 91%

Spermidine coupled with exercise rescues skeletal muscle atrophy from D-gal-induced aging rats through enhanced autophagy and reduced apoptosis via AMPK-FOXO3a signal pathway

et al. 2017

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“…Mitochondria are the cellular power sources, for they produce ATP. Mitochondrial oxidative damage and CD accumulation may lead to energy deficiency and mitochondrial dysfunction (Du et al 2015(Du et al , 2019b. Specifically, the oxidation-damaged mitochondria produce less ATP and have a reduced MMP.…”

Section: Discussionmentioning

confidence: 99%

d-Galactose-induced oxidative stress and mitochondrial dysfunction in the cochlear basilar membrane: an in vitro aging model

Guo

Zhan

et al. 2020

Biogerontology

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The cochlear basilar membrane (CBM) contains inner hair cells and outer hair cells that convert sound waves into electrical signals and transmit them to the central auditory system. Cochlear aging, the primary reason of age-related hearing loss, can reduce the signal transmission capacity. There is no ideal in vitro aging model of the CBM. In this study, we cultured the CBM, which was dissected from the cochlea of the C57BL/6 mice 5 days after birth, in a medium containing 20 mg/mL, 40 mg/mL, or 60 mg/ mL D-galactose (D-gal). Compared with the control group, the levels of senescence-associated b-galactosidase were increased in a concentration-dependent manner in the CBM of the D-gal groups. In addition, levels of the mitochondrial superoxide and patterns of an age-related mitochondrial DNA3860-bp deletion were significantly increased. The ATP levels and the membrane potential of the mitochondrial were significantly decreased in the CBM of the D-gal groups compared with the control group. Furthermore, in comparison with the control group, damaged hair cell stereocilia and a loss of inner hair cell ribbon synapses were observed in the CBM of the D-gal groups. A loss of hair cells and activation of caspase-3-mediated outer hair cell apoptosis were also observed in the CBM of the high-dose D-gal group. These insults induced by D-gal in the CBM in vitro were similar to the ones that occur in cochlear natural aging in vivo. Thus, we believe that this is a successful in vitro aging model using cultured CBM. These results demonstrate

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“…While the mechanisms of D-gal-induced hearing dysfunction remains to be further defined, it has been reported that D-gal caused a significant increase in the expression of NADPH oxidase (NOX2) and 8-hydroxy-2-deoxyguanosine, a biomarker of DNA oxidative damage, as well as a decrease in the mitochondrial total antioxidant capabilities in the auditory cortex, as compared with the control rats. 1 Previous studies have also shown that D-gal reacts with the free amines of amino acids in proteins and peptides to form advanced glycation end products, which mediates downstream inflammatory signaling pathways, such as NF-kB, and induce release of pro-inflammatory cytokines such as TNF-a, IL-1b, and IL-6. 16,17 Here, we also found that D-gal upregulated pro-inflammatory cytokine gene expression in the cochlear tissues and activation of NF-kB in the Schwann cells, suggesting D-gal-induced chronic inflammation through NK-kB signaling pathway may be involved in the pathogenesis of hearing dysfunction in the rat models.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effect of Huperzine A on d-Galactose-Induced Hearing Dysfunction

Shi

2019

Ear Nose Throat J

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Background: Administration of d-galactose (d-gal) has been used to create animal models of neurodegenerative diseases, and huperzine A has been used to treat the neurodegenerative diseases such as Alzheimer disease. Methods: An animal model of hearing dysfunction was established by administration of d-gal in the rats, and the effect of huperzine A on d-gal-induced abnormal hearing function and cochlear damage was investigated. Senescence of the cochlear tissues was examined by β-galactase staining, and messenger RNA expression of inflammatory cytokines was quantified by real-time reverse transcription-polymerase chain reaction (RT-PCR). Results: It was found that d-gal significantly increased auditory brainstem response (ABR) threshold and cellular senescence and decreased neurofilament in the cochlear tissues. Huperzine A could significantly attenuate d-gal-induced increase of ABR threshold and cellular senescence as well as reduction of neurofilament. Moreover, huperzine A could inhibit d-gal-induced activation of nuclear factor kappa-B (NF-κB) in Schwann cells and significantly blocked d-gal-stimulated gene expression of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. Conclusion: These findings suggested that d-gal causes hearing dysfunction by inflammatory injury of cochlear neurons and that huperzine A could prevent hearing loss by protecting d-gal-induced physical damage of cochlear tissues.

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NADPH oxidase 2-dependent oxidative stress, mitochondrial damage and apoptosis in the ventral cochlear nucleus of d-galactose-induced aging rats

Cited by 43 publications

References 37 publications

Spermidine coupled with exercise rescues skeletal muscle atrophy from D-gal-induced aging rats through enhanced autophagy and reduced apoptosis via AMPK-FOXO3a signal pathway

Spermidine coupled with exercise rescues skeletal muscle atrophy from D-gal-induced aging rats through enhanced autophagy and reduced apoptosis via AMPK-FOXO3a signal pathway

d-Galactose-induced oxidative stress and mitochondrial dysfunction in the cochlear basilar membrane: an in vitro aging model

Neuroprotective Effect of Huperzine A on d-Galactose-Induced Hearing Dysfunction

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