Oxidative stress and mitochondrial damage: importance in non-SOD1 ALS

Carrı̀, Maria Teresa; Valle, Cristiana; Bozzo, Francesca; Cozzolino, Mauro

doi:10.3389/fncel.2015.00041

Cited by 84 publications

(74 citation statements)

References 59 publications

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“…ALS (amyotrophic lateral sclerosis), schizophrenia, mitochondrial disorders, hypertension and diabetes [1][2][3][4][5][6][7][8][9][10][11][12][13]. Dickens et al [14] reported that MD in vitro enhances intracellular ROS production leading to endogenous OS in endothelial cells, and Garcia et al [15] showed that Mg 2+ supplementation reduces ROS formation in mitochondria.…”

Section: Introductionmentioning

confidence: 99%

PARK7/DJ-1 dysregulation by oxidative stress leads to magnesium deficiency: implications in degenerative and chronic diseases

et al. 2015

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Disturbed magnesium (Mg(2+)) homoeostasis and increased levels of OS (oxidative stress) are associated with poor clinical outcomes in patients suffering from neurodegenerative, cardiovascular and metabolic diseases. Data from clinical and animal studies suggest that MD (Mg(2+) deficiency) is correlated with increased production of ROS (reactive oxygen species) in cells, but a straightforward causal relationship (including molecular mechanisms) between the two conditions is lacking. The multifactorial protein PARK7/DJ-1 is a major antioxidant protein, playing a key role in cellular redox homoeostasis, and is a positive regulator of AR (androgen receptor)-dependent transcription. SLC41A1 (solute carrier family 41 member 1), the gene encoding a ubiquitous cellular Mg(2+)E (Mg(2+)efflux) system, has been shown to be regulated by activated AR. We hypothesize that overexpression/up-regulation of PARK7/DJ-1, attributable to OS and related activation of AR, is an important event regulating the expression of SLC41A1 and consequently, modulating the Mg(2+)E capacity. This would involve changes in the transcriptional activity of PARK7/DJ-1, AR and SLC41A1, which may serve as biomarkers of intracellular MD and may have clinical relevance. Imipramine, in use as an antidepressant, has been shown to reduce the Mg(2+)E activity of SLC41A1 and OS. We therefore hypothesize further that administration of imipramine or related drugs will be beneficial in MD- and OS-associated diseases, especially when combined with Mg(2+) supplementation. If proved true, the OS-responsive functional axis, PARK7/DJ-1-AR-SLC41A1, may be a putative mechanism underlying intracellular MD secondary to OS caused by pro-oxidative stimuli, including extracellular MD. Furthermore, it will advance our understanding of the link between OS and MD.

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Section: Introductionmentioning

confidence: 99%

PARK7/DJ-1 dysregulation by oxidative stress leads to magnesium deficiency: implications in degenerative and chronic diseases

et al. 2015

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“…Results showed H 2 O 2 -induced alterations of cell viability and percentage of apoptotic cells were both attenuated by LBPs, suggesting the neuroprotective role of LBPs in PC-12 cells. Mitochondrial dysfunction is associated with oxidative stress-induced pathology [30]. The mitochondrial pathway is also termed as intrinsic or Bcl-2-regulated pathway, in which Bcl-2 proteins and diverse caspases were involved [31].…”

Section: Discussionmentioning

confidence: 99%

Lycium Barbarum Polysaccharides Alleviates Oxidative Damage Induced by H2O2 Through Down-Regulating MicroRNA-194 in PC-12 and SH-SY5Y Cells

Niu

Jin

Niu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Currently, scientists attempt to improve outcome of spinal cord injury (SCI) via reducing secondary injury during SCI. Oxidative stress is critical for pathophysiology of secondary damage, thus we mainly focused on the anti-oxidant effects of Lycium barbarum polysaccharides (LBPs) on PC-12 and SH-SY5Y cells as well as the underlying mechanisms. Methods: Oxidative stress was induced by H₂O₂ stimulation. Effects of LBPs on cell viability, apoptosis, and expression of proteins associated with apoptosis and autophagy in H₂O₂-induced cells were assessed by CCK-8 assay, flow cytometry assay and Western blot analysis, respectively. Then, expression of miR-194 was determined by qRT-PCR. Expression of miR-194 was dysregulated, and whether LBPs affected H₂O₂-treated cells through modulating miR-194 was verified. The expression of key kinases in the PI3K/AKT pathway and the intracellular levels of ROS and NO were testified by Western blot analysis and flow cytometry with fluorescent probes. Results: H₂O₂-induced decrease of cell viability and increases of apoptosis and autophagy in PC-12 cells were mitigated by LBPs treatment. Next, we found that miR-194 expression was both down-regulated by LBPs treatment in PC-12 and SH-SY5Y cells. More experiments consolidated that influence of LBPs on H₂O₂-treated cells was reversed by miR-194 overexpression while was augmented by miR-194 inhibition. LBPs elevated the phosphorylated levels of PI3K and AKT and reduced levels of ROS and NO through miR-194. Conclusion: LBPs alleviated H₂O₂-induced decrease of cell viability, and increase of apoptosis and autophagy through down-regulating miR-194. Moreover, LBPs activated the PI3K/AKT pathway and reduced oxidative stress through miR-194.

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“…Oxidative stress (10,11), mitochondrial dysfunction (11,12) and neuroinflammation (13) are believed to play key roles in ALS pathophysiology. HBOT has been shown to modify all of these processes, albeit in small studies.…”

Section: Mechanismmentioning

confidence: 99%