SIRT3 protects cells from hypoxia via PGC-1α- and MnSOD-dependent pathways

Wang, Q.; Li, L.; Li, C.Y.; Pei, Zhong; Zhou, Mi; Li, N.

doi:10.1016/j.neuroscience.2014.11.045

Cited by 67 publications

(52 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…From our limited knowledge, this is the first time that the roles of 6G were approved in hypoxia-treated PC-12 cells through regulation of miR-103/BNIP3. PC-12 cells are classically used to explore the mechanism of neuronal injury induced by hypoxia [17,18]. In our present study, firstly, the effects of 6G on hypoxia-treated PC-12 cells were measured.…”

Section: Discussionmentioning

confidence: 93%

6-Gingerols (6G) reduces hypoxia-induced PC-12 cells apoptosis and autophagy through regulation of miR-103/BNIP3

Kang

Han

Zhang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

View full text Add to dashboard Cite

2019) 6-Gingerols (6G) reduces hypoxia-induced PC-12 cells apoptosis and autophagy through regulation of miR-103/BNIP3, Artificial ABSTRACT Finding novel therapeutic agent for the treatment of cerebral ischemia is urgently required. These experiments explored the potential roles of 6-Gingerols (6G) in hypoxia-stimulated rat PC-12 cells. Cell viability, apoptosis and its related proteins were studied by the approaches of MTT assay, flow cytometry assay and Western blot analysis, respectively. In addition, whether 6G achieved its functions in hypoxia-induced injury through miR-103 was illustrated. Moreover, the associated signalling pathways were investigated. Obviously, hypoxia treatment blocked cell viability and enhanced apoptosis while this trend was ameliorated by 6G. Then we observed that hypoxia administration up-regulated miR-103 expression and 6G could further increase miR-103 expression in hypoxia-stimulated PC-12 cells. Inhibition of miR-103 attenuated the neuroprotective effects of 6G on hypoxia-treated PC-12 cells. Moreover, Bcl2/adenovirus EIB 19kD-interacting protein 3 (BNIP3) was a target of miR-103 and BNIP3 upregulation also attenuated the neuroprotective impact of 6G on hypoxia-treated PC-12 cells. Hypoxia activated the p38MAPK and JNK pathways were inactivated by 6G. To sum up, 6G protected hypoxiastimulated PC-12 cells through miR-103-mediatated down-regulation of BNIP3 by inhibiting p38 MAPK and JNK pathways. HIGHLIGHTS 1. 6-Gingerols (6G) is a promising agent for cerebral ischemia therapy. 2. The neuroprotective effects of 6G are mediated by miR-103 and BNIP3. 3. Up-regulation of miR-103 exerts neuroprotective effects. ARTICLE HISTORY

show abstract

Section: Discussionmentioning

confidence: 93%

6-Gingerols (6G) reduces hypoxia-induced PC-12 cells apoptosis and autophagy through regulation of miR-103/BNIP3

Kang

Han

Zhang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

View full text Add to dashboard Cite

show abstract

“…Previous studies showed that PGC1 exert stimulatory effect on Sirt3 promoter and act as an upstream activator of Sirt3 expression in hepatocytes and muscle cells [32]. In contrast, Sirt3 could also protect neuronal cells through PGC1-mediated antioxidative activities [33], [34]. Increased levels of PGC1 and Sirt3 were shown to modulate mitochondrial metabolic activity and oxidative stress regulator pathway activation, acting as ROS suppressors by increasing the expression and activity of glutathione peroxidase (GPX) and superoxide dismutase 2 (SOD2) [35], [36].…”

Section: Discussionmentioning

confidence: 99%

Sirt1-Sirt3 axis regulates human blood-brain barrier permeability in response to ischemia

et al. 2018

View full text Add to dashboard Cite

Sirtuin1 (Sirt1) and Sirtuin3 (Sirt3) are two well-characterized members of the silent information regulator 2 (Sir2) family of proteins. Both Sirt1 and Sirt3 have been shown to play vital roles in resistance to cellular stress, but the interaction between these two sirtuins has not been fully determined. In this study, we investigated the role of Sirt1-Sirt3 axis in blood-brain barrier (BBB) permeability after ischemia in vitro. Human brain microvascular endothelial cells and astrocytes were co-cultured to model the BBB in vitro and oxygen and glucose deprivation (OGD) was performed to mimic ischemia. The results of transepithelial electrical resistance (TEER) showed that suppression of Sirt1 via siRNA or salermide significantly decreased BBB permeability, whereas Sirt3 knockdown increased BBB permeability. In addition, Sirt1 was shown to regulate Sirt3 expression after OGD through inhibiting the AMPK-PGC1 pathway. Application of the AMPK inhibitor compound C partially prevented the effects of Sirt1-Sirt3 axis on BBB permeability after OGD. The results of flow cytometry and cytochrome c release demonstrated that Sirt1 and Sirt3 exert opposite effects on OGD-induced apoptosis. Furthermore, suppression of Sirt1 was shown to attenuate mitochondrial reactive oxygen species (ROS) generation, which contribute to the Sirt1-Sirt3 axis-induced regulation of BBB permeability and cell damage. In summary, these findings demonstrate that the Sirt1-Sirt3 axis might act as an important modulator in BBB physiology, and could be a therapeutic target for ischemic stroke via regulating mitochondrial ROS generation.

show abstract

“…In the present study, we for the first time confirmed that the expression of SIRT3 was decreased in cortical neurons secondary to EBI after SAH in a time-dependent manner. Furthermore, recently a positive relationship between SIRT3 and MnSOD was observed, suggesting that SIRT3 could act as a pivotal antioxidant factor during EBI following SAH [32]. …”

Section: Discussionmentioning

confidence: 99%

“…For example, an in vitro experiment showed that the overexpression of SIRT3 diminishes the sensitivity of PC12 neurons to both oxidative and apoptotic insults. Meanwhile, another study reported that SIRT3 protects PC12 cells against hypoxia damage through PGC-1a and MnSOD pathways by reducing ROS and maintaining ATP production [32]. …”

Section: Discussionmentioning

confidence: 99%

SIRT3 Expression Decreases with Reactive Oxygen Species Generation in Rat Cortical Neurons during Early Brain Injury Induced by Experimental Subarachnoid Hemorrhage

Huang

et al. 2016

BioMed Research International

View full text Add to dashboard Cite

Sirtuin3 (SIRT3) is an important protein deacetylase which predominantly presents in mitochondria and exhibits broad bioactivities including regulating energy metabolism and counteracting inflammatory effect. Since inflammatory cascade was proved to be critical for pathological damage following subarachnoid hemorrhage (SAH), we investigated the overall expression and cell-specific distribution of SIRT3 in the cerebral cortex of Sprague-Dawley rats with experimental SAH induced by internal carotid perforation. Results suggested that SIRT3 was expressed abundantly in neurons and endothelia but rarely in gliocytes in normal cerebral cortex. After experimental SAH, mRNA and protein expressions of SIRT3 decreased significantly as early as 8 hours and dropped to the minimum value at 24 h after SAH. By contrast, SOD2 expression increased slowly as early as 12 hours after experimental SAH, rose up sharply at the following 12 hours, and then was maintained at a higher level. In conclusion, attenuated SIRT3 expression in cortical neurons was associated closely with enhanced reactive oxygen species generation and cellular apoptosis, implying that SIRT3 might play an important neuroprotective role during early brain injury following SAH.

show abstract

SIRT3 protects cells from hypoxia via PGC-1α- and MnSOD-dependent pathways

Cited by 67 publications

References 43 publications

6-Gingerols (6G) reduces hypoxia-induced PC-12 cells apoptosis and autophagy through regulation of miR-103/BNIP3

6-Gingerols (6G) reduces hypoxia-induced PC-12 cells apoptosis and autophagy through regulation of miR-103/BNIP3

Sirt1-Sirt3 axis regulates human blood-brain barrier permeability in response to ischemia

SIRT3 Expression Decreases with Reactive Oxygen Species Generation in Rat Cortical Neurons during Early Brain Injury Induced by Experimental Subarachnoid Hemorrhage

Contact Info

Product

Resources

About