Overexpression of DJ-1/PARK7, the Parkinson's disease-related protein, improves mitochondrial function via Akt phosphorylation on threonine 308 in dopaminergic neuron-like cells.

DJ-1/PARK7, the Parkinson's disease-related protein, plays an important role in mitochondrial function. However, the mechanisms by which DJ-1 affects mitochondrial function are not fully understood. Akt is a promoter of neuron survival and is partly involved in the neurodegenerative process. This research aimed at investigating a possible relationship between DJ-1 and Akt signalling in regulating mitochondrial function in the dopaminergic neuron-like cells SH-SY5Y and PC-12. Overexpression of DJ-1 was firstly validated at both the transcriptional and translational levels after transit transfection with plasmid pcDNA3-Flag-DJ-1. Confocal fluorescence microscopy demonstrated that overexpression of DJ-1 increased the mitochondrial mass, but did not disrupt the mitochondrial morphology. In addition, mitochondrial complex I activity was raised in DJ-1-overexpressing cells, and this rise occurred with an increase in cellular adenosine 5'-triphosphate content. Moreover, immunoblotting demonstrated that the levels of phosphoinositide 3-kinase and the total Akt were not altered in DJ-1-overexpressing cells, and nor was the Akt phosphorylation on serine 473 changed. By contrast, Akt phosphorylation on threonine 308 was significantly augmented by overexpression of DJ-1, and the expression of glycogen synthase kinase-3beta, a downstream effector of Akt, was suppressed. In summary, these results suggest that overexpression of DJ-1 improves the mitochondrial function, at least in part, through a mechanism involving Akt phosphorylation on threonine 308.

Effects of online mindfulness-based interventions on the mental health of university students: A systematic review and meta-analysis.

Objectives: Mental health problems among university students are a cause of widespread concern. Mindfulness-based interventions (MBIs) delivered online have considerable potential to help university students manage mental health challenges. However, there is no consensus regarding the efficacy of online MBIs. This meta-analysis aims to determine whether MBIs are feasible and effective for improving university students' mental health. Methods: Randomised controlled trials (RCTs) in Web of Science, PubMed, Cochrane Library, Embase and the US National Library of Medicine (Clinical Trial Registry) published through August 31, 2022, were searched. Two reviewers selected the trials, conducted a critical appraisal, and extracted the data. Nine RCTs met our inclusion criteria. Results: This analysis showed that online MBIs were effective in improving depression (standardised mean difference [SMD] = -0.27; 95% confidence interval [CI], -0.48 to -0.07; P = 0.008), anxiety (SMD = -0.47; 95% CI, -080 to -0.14; P = 0.006), stress (SMD = -0.58; 95% CI, -0.79 to -0.37; P < 0.00001), and mindfulness (SMD = 0.71; 95% CI, 0.17 to 1.25; p = 0.009) in university students. No significant effect was found on wellbeing (SMD = 0.30; 95% CI, -0.00 to 0.60; P = 0.05). Conclusion: The findings indicated that online MBIs could effectively improve the mental health of university students. Nevertheless, additional rigorously designed RCTs are required. Systematic review registration: https://inplasy.com/inplasy-2022-9-0099/, identifier INPLASY202290099.

Da-Bu-Yin-Wan Improves the Ameliorative Effect of DJ-1 on Mitochondrial Dysfunction Through Augmenting the Akt Phosphorylation in a Cellular Model of Parkinson's Disease.

Da-Bu-Yin-Wan (DBYW) is recorded originally in China over six centuries ago, and it is used to treat Parkinson's disease (PD) clinically in recent decades. DJ-1 is a homodimeric protein linked to early-onset PD, and found in the mitochondria. In addition, DJ-1 could protect the cells by regulating gene transcription and modulating the Akt signal pathways. Therefore, in this research, we aimed to investigate the ameliorative effect of DBYW on mitochondria in the view of the DJ-1 and Akt signaling. Rat adrenal pheochromocytoma cell line PC-12 was transfected with the plasmid pcDNA3-Flag-DJ-1 (pDJ-1). Subsequently, PC-12 cells were exposed to the PD-related mitochondrial toxin (1-methyl-4-phenylpyridinium) without/with the DBYW. After transfected with the plasmid pDJ-1, the 1-methyl-4-phenylpyridinium-induced toxicity was decreased, and the DJ-1 expression in protein level was increased. DJ-1 overexpression not only increased the mitochondrial mass, but also improved the total ATP content. Moreover, Akt phosphorylation was augmented by DJ-1 overexpression. Additionally, DBYW enhanced the above effects. Conclusively, these findings indicate that DBYW promotes the ameliorative effects of DJ-1 on mitochondrial dysfunction at least through augmenting the Akt phosphorylation in 1-methyl-4-phenylpyridinium-treated PC-12 cells.

Protective effects of DJ-1 medicated Akt phosphorylation on mitochondrial function are promoted by Da-Bu-Yin-Wan in 1-methyl-4-phenylpyridinium-treated human neuroblastoma SH-SY5Y cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Da-Bu-Yin-Wan (DBYW), a historically traditional Chinese medicine formula, was originally defined over 600 years ago. In recent decades, DBYW was clinically employed to treat Parkinson's disease (PD). AIM OF THE STUDY: To explore the underlying mechanism of DBYW on mitochondrial function, we investigated the effect of DBYW on mitochondrial function from the perspectives of DJ-1 and Akt signaling. MATERIALS AND METHODS: Human derived neuroblastoma SH-SY5Y cells were transiently transfected with the plasmid pcDNA3-Flag-DJ-1 aimed to overexpress the DJ-1 protein. Transfected cells were treated with 1-methyl-4-phenylpyridinium (MPP(+)), a PD-related mitochondrial complex I inhibitor, in the absence and presence of DBYW. The cell viability was assessed by Cell Counting Kit-8 assay. The protein expressions of DJ-1 and Akt signaling were examined by western blotting. The mitochondrial mass was evaluated by confocal fluorescence microscopy. The mitochondrial complex I activity and cellular ATP content were measured by commercial kits. RESULTS: Transfection with pcDNA3-Flag-DJ-1 decreased the MPP(+)-induced toxicity and overexpressed the DJ-1. In DJ-1 overexpressed cells, the mitochondrial mass was raised, mitochondrial complex I activity was improved, and cellular ATP content was increased. In addition, overexpression of DJ-1 augmented the Akt phosphorylation on threonine 308 and serine 473. Moreover, DBYW promoted the above effects in DJ-1 expressed cells. CONCLUSIONS: These data suggest that DJ-1 protects the mitochondrial function by medicating Akt phosphorylation in MPP(+)-treated SH-SY5Y cells. Moreover, DBYW enhances the protective effect of DJ-1 medicated Akt phosphorylation on mitochondrial function.

Da-bu-yin-wan and qian-zheng-san to neuroprotect the mouse model of Parkinson's disease.

Da-Bu-Yin-Wan (DBYW) and Qian-Zheng-San (QZS), two classic traditional Chinese medicinal formulas, were clinically employed to treat Parkinson's disease (PD). Our previous studies demonstrated neuroprotective effects of them on mitochondrial function in PD mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The purpose of this research was to investigate their possible mechanisms in the light of mitochondrial ATP-sensitive potassium (mitoKATP) channels. The neuroprotective effect of DBYW and QZS on dopamine (DA) neurons in substantia nigra (SN) in the MPTP-induced PD mice was investigated by behavioral test (pole test) and immunohistochemistry. Adenosine triphosphate (ATP) level in the midbrain tissue was detected by firefly luciferase method. MitoKATP channel subunits SUR1 and Kir6.2 mRNA and protein expressions were tested by real-time PCR (RT-PCR) and Western blot. It was observed that DBYW and/or QZS served to ameliorate MPTP-induced behavioral impairment and prevent the loss of substantia nigra dopamine neurons, as well as increase ATP level in the midbrain tissue and downregulate SUR1 expression at mRNA and protein levels with no marked influence on Kir6.2. We concluded that DBYW and QZS exhibit neuroprotective effects probably through the regulation of ATP level and mitoKATP channel subunit expressions.

Da-Bu-Yin-Wan and Qian-Zheng-San, two traditional Chinese herbal formulas, up-regulate the expression of mitochondrial subunit NADH dehydrogenase 1 synergistically in the mice model of Parkinson's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Da-Bu-Yin-Wan (DBYW) and Qian-Zheng-San (QZS), two traditional Chinese herbal formulas, were clinically employed to treat Parkinson's disease (PD) for decades. AIM OF THE STUDY: Our previous studies demonstrated neuroprotective effects of DBYW and QZS on mitochondrial function in mice model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In present research, we aimed to investigate the possible neuroprotective mechanisms of DBYW and QZS. MATERIALS AND METHODS: The effects of DBYW and QZS on the behavioral changes (pole test), expression of tyrosine hydroxylase (TH) of substantia nigra by immunohistochemistry, monoaminergic contents and activity of striatum by high performance liquid chromatography, neuronal ultrastructure changes by transmission electron microscopy, mitochondrial DNA (mtDNA) damage by long-extension polymerase chain reaction (PCR), and mRNA expression of mitochondrial subunit NADH dehydrogenase 1(ND1) by qualitative real-time PCR were investigated. RESULTS: Present study demonstrated that DBYW and QZS not only ameliorated the behavior induced by the administration of MPTP and synergistically prevented the decreasing of TH expression, but also increased monoaminergic contents and activity, improved the ultrastructural changes, decreased the mtDNA damage, and synergistically up-regulated the expression of ND1 in mRNA level. CONCLUSIONS: These results suggest that DBYW and QZS possess anti-parkinsonism and neuroprotective properties.