Mu-Xiang-You-Fang protects PC12 cells against OGD/R-induced autophagy via the AMPK/mTOR signaling pathway

Ma, Huixia; Hou, Fan Fan; Chen, Ailing; Li, Tingting; Zhu, Yu; Zhao, Qipeng

doi:10.1016/j.jep.2020.112583

Cited by 19 publications

(12 citation statements)

References 44 publications

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“…. It is well known that OGD/R-induced cell injury is mainly characterized by a decreased cell viability and increased apoptosis rate and LDH release level (Huang and Hu, 2018;Ma et al, 2020), and our results were consistent with previous studies. Meanwhile, significant cerebral infarction lesions were observed by TTC staining of the rats' brain tissues, suggesting the establishment of a successful in vivo model.…”

Section: )supporting

confidence: 93%

Olfactory Mucosa Mesenchymal Stem Cells Alleviate Cerebral Ischemia/Reperfusion Injury Via Golgi Apparatus Secretory Pathway Ca2+ -ATPase Isoform1

Liu

Huang

et al. 2020

Front. Cell Dev. Biol.

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Olfactory mucosa mesenchymal stem cells (OM-MSCs) have exhibited their effectiveness in central nervous system diseases and provided an appealing candidate for the treatment of ischemic stroke. Previous evidence have shown that Golgi apparatus (GA) secretory pathway Ca 2+ -ATPase isoform1 (SPCA1) was a potential therapeutic target for ischemic stroke. In this study, we explored the neuroprotective mechanism of OM-MSCs and its effect on the expression and function of SPCA1 during cerebral ischemia/reperfusion. Based on in vitro and in vivo experiments, we discovered that OM-MSCs attenuated apoptosis and oxidative stress in ischemic stroke models, reduced the cerebral infarction volume, and improved the neurologic deficits of rats. OM-MSCs also upregulated SPCA1 expression and alleviated Ca 2+ overload and decreased the edema and dissolution of the GA in neurons. Moreover, we discovered that SPCA1 depletion in oxygen and glucose deprivation/reoxygenation (OGD/R)-treated N2a cells mitigated the protective effects of OM-MSCs. Altogether, OM-MSCs exerted neuroprotective effects in ischemic stroke probably via modulating SPCA1 and reducing the edema and dissolution of the GA in neurons.

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Section: )supporting

confidence: 93%

Olfactory Mucosa Mesenchymal Stem Cells Alleviate Cerebral Ischemia/Reperfusion Injury Via Golgi Apparatus Secretory Pathway Ca2+ -ATPase Isoform1

Liu

Huang

et al. 2020

Front. Cell Dev. Biol.

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“…AMPK could promote autophagy by phosphorylating autophagy-related proteins, such as mTOR, which induced initial phagophore formation [ 29 ]. A previous study has reported that the AMPK/mTOR pathway mediates OGD-R-induced cell injury by promoting autophagosome formation [ 30 ]. Since our above data has demonstrated that TRPM2 plays an inhibitory role in OGD-R-induced autophagy induction, we are wondering whether TRPM2 affects autophagy by regulating the AMPK/mTOR pathway.…”

Section: Resultsmentioning

confidence: 99%

Deficiency of ROS‐Activated TRPM2 Channel Protects Neurons from Cerebral Ischemia‐Reperfusion Injury through Upregulating Autophagy

Liu

et al. 2021

Oxidative Medicine and Cellular Longevity

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Cerebral ischemia-reperfusion (I-R) transiently increased autophagy by producing excessively reactive oxygen species (ROS); on the other hand, activated autophagy would remove ROS-damaged mitochondria and proteins, which led to cell survival. However, the regulation mechanism of autophagy activity during cerebral I-R is still unclear. In this study, we found that deficiency of the TRPM2 channel which is a ROS sensor significantly decreased I-R-induced neuronal damage. I-R transiently increased autophagy activity both in vitro and in vivo. More importantly, TRPM2 deficiency decreased I-R-induced neurological deficit score and infarct volume. Interestingly, our results indicated that TRPM2 deficiency could further activate AMPK rather than Beclin1 activity, suggesting that TRPM2 inhibits autophagy by regulating the AMPK/mTOR pathway in I-R. In conclusion, our study reveals that ROS-activated TRPM2 inhibits autophagy by downregulating the AMPK/mTOR pathway, which results in neuronal death induced by cerebral I-R, further supporting that TRPM2 might be a potential drug target for cerebral ischemic injury therapy.

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“…Therefore, 5 µM CT has a better anti-apoptotic effect than 10 µM CT. MMP is a sensitive indicator reflecting mitochondrial function. The decrease in MMP leads to instability of neuronal cell structure, thereby causing cell damage and ultimately results in cell death (22). A recent study has confirmed that OGD/R may cause intracellular [Ca 2+ ] overload and lead to mitochondrial dysfunction, resulting in unstable neuronal cell structure and ultimately leading to neuronal apoptosis (32).…”

Section: Discussionmentioning

confidence: 99%

“…After 12 h of adhering, to initiate oxygen-glucose deprivation (OGD) by replacing the cell culture medium with the glucose-free medium, the cells were incubated for 2 h in an oxygen-free chamber (5% CO 2 ; 95% N 2 ) at 37˚C. At the end of the OGD period, the cells were incubated under normal growth conditions (5% CO 2 and 95% O 2 ) for 24 h to achieve reperfusion (R) (22). Cells in the experimental groups were treated with CT (2.5, 5 or 10 µM) and Nimodipine (5 µM) during the entire period of OGD/R.…”

Section: Drugsmentioning

confidence: 99%

Costunolide attenuates oxygen‑glucose deprivation/reperfusion‑induced mitochondrial‑mediated apoptosis in PC12 cells

Meng

et al. 2021

Mol Med Rep

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The present study investigated the effect of costunolide (CT), a compound extracted from Aucklandia lappa Decne, to attenuate oxygen-glucose deprivation/reperfusion (OGD/R)-induced mitochondrial-mediated apoptosis in PC12 cells. The present study used molecular docking technology to detect the binding of CT with mitochondrial apoptotic protein targets. A model of oxygen-glucose deprivation for 2 h and reperfusion for 24 h in PC12 cells was used to mimic cerebral ischemic injury. Cell viability and damage were measured using the Cell Counting kit-8 and lactate dehydrogenase (LDH) cytotoxicity assay kits. Cellular apoptosis was analyzed using flow cytometry. A fluorescence microscope determined intracellular [Ca 2+ ] and mitochondrial membrane potential. Furthermore, immunofluorescence and Western blot analyses were used to detect the expression of apoptosis-associated proteins. CT contains binding sites with Caspase-3, Caspase-9 and Caspase-7. CT markedly enhanced cell viability, inhibited LDH leakage, increased intracellular [Ca 2+ ], stabilized the mitochondrial membrane potential, increased the expression of Bcl-2 and inhibited the expression of Apaf-1, Bax, cleaved-caspase-7, cleaved-caspase-9 and cleaved-caspase-3. CT may markedly protect PC12 cells from damage caused by OGD/R, and its mechanism is associated with blocking the calcium channel and inhibiting mitochondrial-mediated apoptosis.

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Mu-Xiang-You-Fang protects PC12 cells against OGD/R-induced autophagy via the AMPK/mTOR signaling pathway

Cited by 19 publications

References 44 publications

Olfactory Mucosa Mesenchymal Stem Cells Alleviate Cerebral Ischemia/Reperfusion Injury Via Golgi Apparatus Secretory Pathway Ca2+ -ATPase Isoform1

Olfactory Mucosa Mesenchymal Stem Cells Alleviate Cerebral Ischemia/Reperfusion Injury Via Golgi Apparatus Secretory Pathway Ca2+ -ATPase Isoform1

Deficiency of ROS‐Activated TRPM2 Channel Protects Neurons from Cerebral Ischemia‐Reperfusion Injury through Upregulating Autophagy

Costunolide attenuates oxygen‑glucose deprivation/reperfusion‑induced mitochondrial‑mediated apoptosis in PC12 cells

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