Age-Related Decrease in the Mitochondrial Sirtuin Deacetylase Sirt3 Expression Associated with ROS Accumulation in the Auditory Cortex of the Mimetic Aging Rat Model

Zeng, Lingling; Yang, Yang; Hu, Yuxia; Sun, Yu; Du, Zhongtao; Xie, Zhen; Zhou, Tao; Kong, Weijia

doi:10.1371/journal.pone.0088019

Cited by 89 publications

(81 citation statements)

References 63 publications

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“…After treated with D -gal, pathology of central presbycusis demonstrated increased neural apoptosis and neural damage as well as a decreased number of neurons in the auditory cortex and exhibited degraded cognitive function, which is similar with the natural aging process [27], [29], [30]. Additionally, our previous study also replicate the central presbycusis with D -gal and causes accumulation of the CD that was also observed in the natural aging animals [29], [31]. In our study, we explored the in vitro and in vivo mechanism for whether and how H 2 S acts on contributors of aging in the auditory cortex using a mimetic aging model induced by D -gal.…”

Section: Introductionmentioning

confidence: 71%

The role of sodium hydrosulfide in attenuating the aging process via PI3K/AKT and CaMKKβ/AMPK pathways

et al. 2017

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Age-related dysfunction of the central auditory system, known as central presbycusis, is characterized by defects in speech perception and sound localization. It is important to determine the pathogenesis of central presbycusis in order to explore a feasible and effective intervention method. Recent work has provided fascinating insight into the beneficial function of H2S on oxidative stress and stress-related disease. In this study, we investigated the pathogenesis of central presbycusis and tried to explore the mechanism of H2S action on different aspects of aging by utilizing a mimetic aging rat and senescent cellular model. Our results indicate that NaHS decreased oxidative stress and apoptosis levels in an aging model via CaMKKβ and PI3K/AKT signaling pathways. Moreover, we found that NaHS restored the decreased activity of antioxidants such as GSH, SOD and CAT in the aging model in vivo and in vitro by regulating CaMKKβ and PI3K/AKT. Mitochondria function was preserved by NaHS, as indicated by the following: DNA POLG and OGG-1, the base excision repair enzymes in mitochondrial, were upregulated; OXPHOS activity was downregulated; mitochondrial membrane potential was restored; ATP production was increased; and mtDNA damage, indicated by the common deletion (CD), declined. These effects were also achieved by activating CaMKKβ/AMPK and PI3K/AKT signaling pathways. Lastly, protein homeostasis, indicated by HSP90 alpha, was strengthened by NaHS via CaMKKβ and PI3K/AKT. Our findings demonstrate that the ability to resist oxidative stress and mitochondria function are both decreased as aging developed; however, NaHS, a novel free radical scavenger and mitochondrial protective agent, precludes the process of oxidative damage by activating CaMKKβ and PI3K/AKT. This study might provide a therapeutic target for aging and age-related disease.

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Section: Introductionmentioning

confidence: 71%

The role of sodium hydrosulfide in attenuating the aging process via PI3K/AKT and CaMKKβ/AMPK pathways

et al. 2017

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“…A study has been reported that sirt3 expression is decreased with aging [25]. Moreover, the sirt3 coding sequence links to human aging [26].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Sirt3 Expression is Decreased in APP/PS1 Double Transgenic Mouse Model of Alzheimer’s Disease

et al. 2015

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Emerging data suggests that mitochondrial dysfunction is prominently involved in Alzheimer disease (AD) progression. Sirtuin-3 (Sirt3) is a member of the sirtuin family of nicotinamide adenine dinucleotide dependent deacetylases that regulates a variety of mitochondrial functions and suppresses mitochondria-related physiology. Here, we determined sirt3 expression in a mouse model of AD. Spatial learning and memory were tested by Morris water maze in APP/PS1 double transgenic mice. The expression of sirt3 was assayed by real-time quantitative PCR and western blotting. Age-and gender-matched wild-type (WT) littermates were used as controls. Cortical sirt3 localization was assessed using immunohistochemistry. The expression of sirt3 mRNA was significantly lower in the cortex of APP/PS1 double transgenic mice than in WT littermates (0.83 ± 0.24 vs. 1.10 ± 0.21, P < 0.05). A comparable reduction was found in sirt3 protein levels using western blotting. The ratio of mean optical density (MOD) of total sirt3/β-actin in the cortex was 0.77 ± 0.11 in APP/PS1 double transgenic mice and 1.34 ± 0.17 in the WT littermates (P < 0.01). Immunohistochemistry showed the same change as western blotting. The ratio of MOD of integral optical density/total area in APP/PS1 and WT littermates was 0.58 ± 0.02 and 0.71 ± 0.05 (P < 0.01). These data show that sirt3 was depleted in APP/PS1 double transgenic mice. The results suggest that mitochondrial sirt3 might participate in the development of AD via mitochondrial dysfunction.

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“…When SIRT3 enters into mitochondria, 142 amino acids are detached from N-terminal by matrix processing peptidase and it is converted to the short active form. Studies have shown that both forms of the enzyme are functional and show enzymatic activity (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). SIRT3 regulates mitochondrial function by deacetylation of mitochondrial proteins.…”

Section: Discussionmentioning

confidence: 99%

Losartan Protects the Heart Against Ischemia Reperfusion Injury: Sirtuin3 Involvement

et al. 2015

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-PURPOSE:Sirtuin-3 (SIRT3) deacetylase protects the heart against oxidative stress via survival factors upregulation. Clinical and experimental studies have demonstrated that activation of systemic and local renin-angiotensin system (RAS) is implicated in ischemia-induced cardiac injury. However, the relation between RAS and SIRT3 in pathophysiology of myocardial ischemia reperfusion is unknown. In this study, the cardiac transcription and expression of SIRT3 levels was examined in response to ischemia reperfusion in untreated and losartan treated rats. METHODS: Rats were divided into control group, losartan group (L), and ischemia reperfusion (IR) groups with (L+IR) or without losatran pretreatment. Some rats were included as sham-operated and saline groups. IR was induced by left anterior descending artery occlusion. SIRT3 protein levels were determined by Western blot technique. The genes expression was specified by realtime RT-PCR. Arrhythmias were assessed according to the Lambeth conventions.

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Age-Related Decrease in the Mitochondrial Sirtuin Deacetylase Sirt3 Expression Associated with ROS Accumulation in the Auditory Cortex of the Mimetic Aging Rat Model

Cited by 89 publications

References 63 publications

The role of sodium hydrosulfide in attenuating the aging process via PI3K/AKT and CaMKKβ/AMPK pathways

The role of sodium hydrosulfide in attenuating the aging process via PI3K/AKT and CaMKKβ/AMPK pathways

Mitochondrial Sirt3 Expression is Decreased in APP/PS1 Double Transgenic Mouse Model of Alzheimer’s Disease

Losartan Protects the Heart Against Ischemia Reperfusion Injury: Sirtuin3 Involvement

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