Mitigative effects of epigallocatechin gallate in terms of diminishing apoptosis and oxidative stress generated by the combination of lead and amyloid peptides in human neuronal cells

2019 ◽  
Vol 33 (11) ◽  
Author(s):  
Neelima Ayyalasomayajula ◽  
Rajanna Ajumeera ◽  
Chetty S. Chellu ◽  
Suresh Challa
Keyword(s):  
Oxidative Stress ◽  
Neuronal Cells ◽  
Epigallocatechin Gallate ◽  
Amyloid Peptides ◽  
Human Neuronal Cells ◽  
And Oxidative Stress

scholarly journals Dihydroceramide desaturase regulates the compartmentalization of Rac1 for neuronal oxidative stress

2020 ◽  
Author(s):  
Fei-Yang Tzou ◽  
Tsu-Yi Su ◽  
Yu-Lian Yu ◽  
Yu-Han Yeh ◽  
Chung-Chih Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Neurological Disorders ◽  
De Novo ◽  
Neuronal Cells ◽  
Membrane Microdomains ◽  
List Type ◽  
Dihydroceramide Desaturase ◽  
Human Neuronal Cells ◽  
And Oxidative Stress

SummaryDisruption of sphingolipid homeostasis has been shown to cause neurological disorders. How specific sphingolipid species modulate the pathogenesis remains unknown. The last step of sphingolipid de novo synthesis is the conversion of dihydroceramide to ceramide catalyzed by dihydroceramide desaturase (human DEGS1; Drosophila Ifc). Loss of ifc leads to dihydroceramide accumulation and oxidative stress, resulting in photoreceptors degeneration, while DEGS1 variants were associated with leukodystrophy and neuropathy. Here, we demonstrated that ifc regulates Rac1 compartmentalization in fly photoreceptors and further showed that dihydroceramide alters the association of active Rac1 to membranes mimicking specific organelles. We also revealed that the major source of ROS originated from Rac1 and NADPH oxidase (NOX) in the cytoplasm, as the NOX inhibitor apocynin ameliorated the oxidative stress and functional defects in both fly ifc-KO photoreceptors and human neuronal cells with disease-associated variant DEGS1H132R. Therefore, DEGS1/ifc deficiency causes dihydroceramide accumulation, resulting in Rac1 translocation and NOX-dependent neurodegeneration.Graphical AbstractADEGS1/ifc converts dihydroceramide to ceramide in neuronal cells, and the endolysosomal NOX complex is not activated.B Dihydroceramide accumulates without functional DEGS1/ifc and causes alterations in membrane microdomains and recruits active Rac1 to endolysosomes. The activation of endolysosomal Rac1-NOX complex elevates cytosolic ROS levels, causing neurodegeneration.In Brief (eTOC blurb)Deficiency in dihydroceramide desaturase causes oxidative stress-mediated neurological disorders. Tzou and Su et al. show that increased dihydroceramide causes the relocalization of active Rac1, whilst inhibition of the Rac1-NOX ameliorates the oxidative stress and neuronal defects. NOX inhibitor apocynin may provide new direction of treatments for patients with DEGS1 variants.HighlightsDeficiency in dihydroceramide (dhCer) desaturase induces cytoplasmic ROS elevationdhCer alters the binding of active Rac1 to reconstituted organelle membranesActive Rac1 is enriched in endolysosomes in ifc-KO neurons for ROS genesisRac1-NADPH oxidase elicits ROS, degenerating leukodystrophy-related neuronal cells

scholarly journals In vitro assessment of the cytotoxic, genotoxic and oxidative stress effects of the synthetic cannabinoid JWH-018 in human SH-SY5Y neuronal cells

2020 ◽  
Vol 9 (6) ◽  
pp. 734-740
Author(s):  
Yigit Sezer ◽  
Ayse Tarbin Jannuzzi ◽  
Marilyn A Huestis ◽  
Buket Alpertunga
Keyword(s):  
Oxidative Stress ◽  
Neuronal Cells ◽  
Underlying Mechanism ◽  
Synthetic Cannabinoid ◽  
Stress Effects ◽  
Legal High ◽  
New Generation ◽  
And Oxidative Stress

Abstract Background: JWH-018 was the first synthetic cannabinoid introduced as a legal high and the first of the new generation of novel psychoactive substances that flooded worldwide drug markets. JWH-018 was marketed as “spice,” “herbal incense,” or “herbal blend,” as a popular and legal (at the time) alternative to cannabis (marijuana). JWH-018 is a potent synthetic cannabinoid with considerable toxicity associated with its use. JWH-018 has qualitatively similar but quantitatively greater pharmacological effects than cannabis, leading to intoxications and even deaths. The mechanisms of action of the drug’s toxicity require research, and thus, the aim of the present study was to investigate the toxicological profile of JWH-018 in human SH-SY5Y neuronal cells. Methods: SH-SY5Y neuronal cells were exposed to increasing concentrations from 5 to 150 μM JWH-018 over 24 h. Cytotoxicity, DNA damage, the apoptotic/necrotic rate, and oxidative stress were assessed following SH-SY5Y exposure. Results: JWH-018 did not produce a significant decrease in SH-SY5Y cell viability, did not alter apoptotic/necrotic rate, and did not cause genotoxicity in SH-SY5Y cells with 24-h exposure. Glutathione reductase and catalase activities were significantly reduced; however, there was no significant change in glutathione peroxidase activity. Also, JWH-018 treatment significantly decreased glutathione concentrations, significantly increased protein carbonylation, and significantly increased malondialdehyde (MDA) concentrations. For significance, all P < 0.05. Discussion/Conclusion: JWH-018 produced oxidative stress in SH-SY5Y cells that could be an underlying mechanism of JWH-018 neurotoxicity. Additional in vivo animal and human-based studies are needed to confirm our findings.

Tubuloside B fromCistanche salsaRescues the PC12 Neuronal Cells from 1-Methyl-4-phenylpyridinium Ion-Induced Apoptosis and Oxidative Stress

Planta Medica ◽  
2002 ◽  
Vol 68 (11) ◽  
pp. 966-970 ◽  
Author(s):  
Guoqing Sheng ◽  
Xiaoping Pu ◽  
Li Lei ◽  
Pengfei Tu ◽  
Changling Li
Keyword(s):  
Oxidative Stress ◽  
Neuronal Cells ◽  
Induced Apoptosis ◽  
And Oxidative Stress
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