L-DOPA causes mitochondrial dysfunction in vitro: a novel mechanism of L-DOPA toxicity uncovered.

L-DOPA causes mitochondrial dysfunction in vitro: a novel mechanism of L-DOPA toxicity uncovered. Int J Biochem Cell Biol. 2019 Oct 22;:105624 Authors: Giannopoulos S, Samardzic K, Raymond BBA, Djordjevic SP, Rodgers KJ Abstract In Parkinson's disease (PD), as in many other neurodegenerative disorders, mitochondrial dysfunction, protein misfolding, and proteotoxic stress underly the disease process. For decades, the primary symptomatic treatment for PD has been the dopamine precursor L-DOPA (Levodopa). L-DOPA however can initiate protein misfolding through its ability to mimic the protein amino acid L-tyrosine, resulting in random errors in aminoacylation and L-DOPA becoming mistakenly inserted into the polypeptide chain of proteins in place of L-tyrosine. In the present study we examined the impact that the generation of DOPA-containing proteins had on human neuroblastoma cell (SH-SY5Y) function in vitro. We showed that even in the presence of antioxidants there was a significant accumulation of cytosolic ubiquitin in DOPA-treated cells, an upregulation in the endosomal-lysosomal degradation system, deleterious changes to mitochondrial morphology and a marked decline in mitochondrial function.The effects of L-DOPA on mitochondrial function were not observed with D-DOPA, the stereoisomer of L-DOPA that cannot be inserted into proteins so did not result from oxidative stress. We could fully protect against these effects by co-treatment with L-tyrosine, su...
Source: The International Journal of Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Int J Biochem Cell Biol Source Type: research

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In this study, 6-OHDA-induced neurotoxicity was analyzed for various cytotoxicity analyses. The genes identified were PINK1 (PTEN-induced kinase 1), PARK7 (Parkinsonism-associated deglycase) and SNCA 1 (alpha synuclein1) validated using CRISPR spcas9 genome editing tool. In this study, Anthraquinone isolated from Pleurotus ostreatus was treated against a dopaminergic neurotoxin, 6-hydroxydopamine (6-OHDA), which induced neurotoxicity in SH-SY5Y cells. Experimental groups in SH-SY5Y neuroblastoma cells were treated with anthraquinone (50 nM) and 6-OHDA (100 nM). MTT and ROS assays were performed to assess the cell viability...
Source: Applied Biochemistry and Biotechnology - Category: Biochemistry Authors: Tags: Appl Biochem Biotechnol Source Type: research
This study demonstrates for the first time that senescent cells secrete functional LTs, significantly contributing to the LTs pool known to cause or exacerbate idiopathic pulmonary fibrosis. Against Senolytics https://www.fightaging.org/archives/2019/11/against-senolytics/ There is no consensus in science that is so strong as to have no heretics. So here we have an interview with a naysayer on the matter of senolytic treatments, who argues that the loss of senescent cells in aged tissues will cause more harm to long-term health than the damage they will do by remaining. To be clear, I think this to be a ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
CONCLUSIONS: Our results indicated that PGC-1α rescues the effects of MPTP-induced mitochondrial dysfunction in C57BL mice. PMID: 31634150 [PubMed - as supplied by publisher]
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
In conclusion, our data show how oncogenic and tumor-suppressive drivers of cellular senescence act to regulate surveillance processes that can be circumvented to enable SnCs to elude immune recognition but can be reversed by cell surface-targeted interventions to purge the SnCs that persist in vitro and in patients. Since eliminating SnCs can prevent tumor progression, delay the onset of degenerative diseases, and restore fitness; since NKG2D-Ls are not widely expressed in healthy human tissues and NKG2D-L shedding is an evasion mechanism also employed by tumor cells; and since increasing numbers of B cells express NKG2D ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
ConclusionsAltogether, this study demonstrates the potent neuroprotective action of amidated PACAP23.General significancePACAP23 represents an attractive template for development of shorter PACAP-derived neuroprotective molecules.
Source: Biochimica et Biophysica Acta (BBA) General Subjects - Category: Biochemistry Source Type: research
Publication date: Available online 27 June 2019Source: Chemico-Biological InteractionsAuthor(s): Marcos Roberto de Oliveira, Izabel Cristina Custódio de Souza, Cristina Ribas FürstenauAbstractDisruption of the mitochondrial function has been associated with redox impairment and triggering of cell death in nucleated human cells, as observed in several diseases. The administration of chemicals that would prevent mitochondrial dysfunction is an attractive strategy in cases of neurodegeneration, cardiovascular diseases, and metabolic disorders. Methylglyoxal (MG) is a dicarbonyl compound that exhibits an important ...
Source: Chemico Biological Interactions - Category: Biochemistry Source Type: research
In vitro 6-hydroxydopamine-induced neurotoxicity: New insights on NFκB modulation. Toxicol In Vitro. 2019 Jun 24;: Authors: Iglesias González Pablo A, Conde Melisa A, Verónica GP, Uranga Romina M, Salvador Gabriela A Abstract Neuronal exposure to 6-hydroxydopamine (6-OHDA), a hydroxylated analog of dopamine, constitutes a very useful strategy for studying the molecular events associated with neuronal death in Parkinson's disease. 6-OHDA increases oxidant levels and impairs mitochondrial respiratory chain, thus promoting neuronal injury and death. Despite the extensive use of 6-OHDA...
Source: Toxicology in Vitro - Category: Toxicology Authors: Tags: Toxicol In Vitro Source Type: research
cke F Abstract Cu isotope fractionation was investigated in the human neuroblastoma SH-SY5Y cell line, in a proliferating/tumor phase (undifferentiated cells), and in a differentiated state (neuron-like cells), induced using retinoic acid (RA). The SH-SY5Y cell line displays genetic aberrations due to its cancerous origin, but differentiation drives the cell line towards phenotypes suitable for the research of neurological diseases (e.g., Alzheimer's disease or Parkinson's disease). Cellular Cu distribution was first explored by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging and, s...
Source: Analytical and Bioanalytical Chemistry - Category: Chemistry Authors: Tags: Anal Bioanal Chem Source Type: research
Nagore Elu1, Nerea Osinalde2, Javier Beaskoetxea1, Juanma Ramirez1, Benoit Lectez1, Kerman Aloria3, Jose Antonio Rodriguez4, Jesus M. Arizmendi1 and Ugo Mayor1,5* 1Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, Spain 2Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain 3Proteomics Core Facility-SGIKER, University of the Basque Country (UPV/EHU), Leioa, Spain 4Department of Genetics, Physical Anthropology and Animal Physiology, University of ...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Da-Bu-Yin-Wan and Qian-Zheng-San Ameliorate Mitochondrial Dynamics in the Parkinson’s Disease Cell Model Induced by MPP+ Cong Gai1†, Wan-Di Feng1†, Tian-Yao Qiang1, Hao-Jie Ma1, Yuan Chai1, Shu-Jing Zhang2, Zhen-Yu Guo1, Jing-Hong Hu2 and Hong-Mei Sun1* 1Department of Anatomy, School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing, China 2Center for Scientific Research, School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing, China To investigate the effect of Da-Bu-Yin-Wan and Qian-Zheng-San (DBYW and QZS) on mitochondrial mass in Parkinson&rsq...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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