Apelin-13 Protects PC12 Cells Against Methamphetamine-Induced Oxidative Stress, Autophagy and Apoptosis

Foroughi, Kobra; Khaksari, Mehdi; Rahmati, Majid; Bitaraf, Fateme Sadat; Shayannia, Asghar

doi:10.1007/s11064-019-02847-9

Cited by 31 publications

(19 citation statements)

References 47 publications

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“…In brain and vascular smooth muscle cells, its antiapoptotic effects are mediated mainly by the APJ receptor and activation on mitogen-activated protein kinase (ERK1/2/MAP3/1) and protein kinase B (AKT) [32,33]. Apelin also has the potential to attenuate oxidative stress, which is linked with apoptosis, as shown in brain cells, adipocytes and bone marrowderived mesenchymal stem cells [34][35][36]. However, the effect of apelin on apoptosis in human placental cells has not yet been investigated.…”

Section: Introductionmentioning

confidence: 99%

Anti-Apoptotic Effect of Apelin in Human Placenta: Studies on BeWo Cells and Villous Explants from Third-Trimester Human Pregnancy

Mlyczyńska

Myszka

Kurowska

et al. 2021

IJMS

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Previously, we demonstrated the expression of apelin and G-protein-coupled receptor APJ in human placenta cell lines as well as its direct action on placenta cell proliferation and endocrinology. The objective of this study was to examine the effect of apelin on placenta apoptosis in BeWo cells and villous explants from the human third trimester of pregnancy. The BeWo cells and villous explants were incubated with apelin (2 and 20 ng/mL) alone or with staurosporine for 24 to 72 h. First, we analysed the dose- and time-dependent effect of apelin on the expression of apoptotic factors on the mRNA level by real-time PCR and on the protein level using Western blot. Next, we checked caspase 3 and 7 activity by Caspase-Glo 3/7, DNA fragmentation by the Cell Death Detection ELISA kit and oxygen consumption by the MitoXpress-Xtra Oxygen Consumption assay. We found that apelin increased the expression of pro-survival and decreased proapoptotic factors on mRNA and protein levels in both BeWo cells and villous explants. Additionally, apelin inhibited caspase 3 and 7 activity and DNA fragmentation in staurosporine-induced apoptosis as also attenuated oxidative stress by increasing extracellular oxygen consumption. The antiapoptotic effect of apelin in BeWo cells was mediated by the APJ receptor and mitogen-activated protein kinase (ERK1/2/MAP3/1) and protein kinase B (AKT). The obtained results showed the antiapoptotic effect of apelin on trophoblast cells, suggesting its participation in the development of the placenta.

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Section: Introductionmentioning

confidence: 99%

Anti-Apoptotic Effect of Apelin in Human Placenta: Studies on BeWo Cells and Villous Explants from Third-Trimester Human Pregnancy

Mlyczyńska

Myszka

Kurowska

et al. 2021

IJMS

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“…METH is toxic to all systems of the body, especially the central nervous system (Yang et al, ). Accumulating evidence shows that METH induces apoptosis, oxidative stress, and mitochondrial dysfunction in vivo and in vitro (Du et al, ; Foroughi, Khaksari, Rahmati, Bitaraf, & Shayannia, ; Shin et al, ; Xu et al, ). Furthermore, METH can lead to the damage of dopaminergic neurons and Parkinson‐like pathology (Biagioni et al, ; Li et al, ).…”

Section: Introductionmentioning

confidence: 99%

Effect of Parkin on methamphetamine‐induced α‐synuclein degradation dysfunction in vitro and in vivo

et al. 2020

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Introduction Methamphetamine (METH) is a psychostimulant drug with complicated neurotoxicity, and abuse of METH is very common. Studies have shown that METH exposure causes alpha‐synuclein (α‐syn) accumulation. However, the mechanism of α‐syn accumulation has not been determined. Methods In this study, we established cell and animal models of METH intoxication to evaluate how METH affects α‐syn expression. In addition, to explore METH‐induced neurotoxicity, we measured the level of Parkin and the phosphorylation levels of α‐syn, Polo‐like kinase 2 (PLK2), the proteasome activity marker CD3δ, and the apoptosis‐related proteins Caspase‐3 and PARP. Parkin is a key enzyme in the ubiquitin–proteasome system. In addition, the effect of Parkin on METH‐induced neurotoxicity was investigated by overexpressing it in vitro and in vivo. Results METH exposure increased polyubiquitin and α‐syn expression, as did MG132. Furthermore, the level of Parkin and the interaction between Parkin and α‐syn decreased after METH exposure. Importantly, the increases in α‐syn expression and neurotoxicity were relieved by Parkin overexpression. Conclusions By establishing stable cell lines and animal models that overexpress Parkin, we confirmed Parkin as an important factor in METH‐induced α‐syn degradation dysfunction in vitro and in vivo. Parkin may be a promising target for the treatment of METH‐induced neurotoxicity.

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“…Apelin-13 attenuated cognitive impairment in 6-hydroxydopamine-produced SN lesions in the rats, as well as antagonized 6-hydroxydopamine-produced neurotoxicity in SH-SY5Y cells [16,40]. Apelin-13 also showed anti-apoptotic properties against neurotoxins MPP+ and methamphetamine 41 . Mitochondrial dysfunction played an important role in the etiology of PD [41,42].…”

Section: Discussionmentioning

confidence: 94%

“…Apelin-13 also showed anti-apoptotic properties against neurotoxins MPP+ and methamphetamine 41 . Mitochondrial dysfunction played an important role in the etiology of PD [41,42]. Rotenone is an environmental neurotoxin that impairs ATP synthesis, and results in mitochondrial dysfunction [43][44][45], which induced the release of cytochrome c, and then promoted cell damage through stimulating a caspase-dependent apoptosis signal.…”

Section: Discussionmentioning

confidence: 97%

Apelin-13 Protects Dopaminergic Neurons against Rotenone—Induced Neurotoxicity through the AMPK/mTOR/ULK-1 Mediated Autophagy Activation

Chen

Wang

Chen

et al. 2020

IJMS

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Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Several brain–gut peptides are able to exert neuroprotective effects on the nigrostriatal dopaminergic system. Apelin-13 is a neuropeptide, conveying potential neuroprotective activities. However, whether, and how, apelin-13 could antagonize rotenone-induced neurotoxicity has not yet been elucidated. In the present study, rotenone-treated SH-SY5Y cells and rats were used to clarify whether apelin-13 has protective effects on dopaminergic neurons, both in vivo and in vitro. The results showed that apelin-13 could protect SH-SY5Y cells from rotenone-induced injury and apoptosis. Apelin-13 was able to activate autophagy, and restore rotenone induced autophagy impairment in SH-SY5Y cells, which could be blocked by the autophagy inhibitor 3-Methyladenine. Apelin-13 activated AMPK/mTOR/ULK-1 signaling, AMPKα inhibitor compound C, as well as apelin receptor blockage via siRNA, which could block apelin-13-induced signaling activation, autophagy activation, and protective effects, in rotenone-treated SH-SY5Y cells. These results indicated that apelin-13 exerted neuroprotective properties against rotenone by stimulating AMPK/mTOR/ULK-1 signaling-mediated autophagy via the apelin receptor. We also observed that intracerebroventricular injection of apelin-13 could alleviate nigrostriatal dopaminergic neuron degeneration in rotenone-treated rats. Our findings provide new insights into the mechanism by which apelin-13 might attenuate neurotoxicity in PD.

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Apelin-13 Protects PC12 Cells Against Methamphetamine-Induced Oxidative Stress, Autophagy and Apoptosis

Cited by 31 publications

References 47 publications

Anti-Apoptotic Effect of Apelin in Human Placenta: Studies on BeWo Cells and Villous Explants from Third-Trimester Human Pregnancy

Anti-Apoptotic Effect of Apelin in Human Placenta: Studies on BeWo Cells and Villous Explants from Third-Trimester Human Pregnancy

Effect of Parkin on methamphetamine‐induced α‐synuclein degradation dysfunction in vitro and in vivo

Apelin-13 Protects Dopaminergic Neurons against Rotenone—Induced Neurotoxicity through the AMPK/mTOR/ULK-1 Mediated Autophagy Activation

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