Mechanical stretch exacerbates the cell death in SH-SY5Y cells exposed to paraquat: mitochondrial dysfunction and oxidative stress

Wang, Fang; Franco, Rodrigo; Skotak, Maciej; Hu, Gang; Chandra, Namas

doi:10.1016/j.neuro.2014.01.002

Cited by 32 publications

(25 citation statements)

References 38 publications

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“…108 Most importantly oxidative stress leads to mitochondrial dysfunction and contributes to chronic neurodegeneration. 109 The mitochondrial transition pore can become damaged leading to an efflux of free radicals. 110 Over time oxidative stress triggers neuronal apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Alzheimer’s disease and chronic traumatic encephalopathy: Distinct but possibly overlapping disease entities

et al. 2016

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Background Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE) have long been recognized as sharing some similar neuropathological features, mainly the presence of neurofibrilary tangles and hyperphosphorylated tau, but have generally been described as distinct entities. Evidence indicates that neurotrauma increases the risk of developing dementia and accelerates the progression of disease. Findings are emerging that CTE and AD may be present in the same patients. Clinical presentation We present a series of previously unpublished cases with one case demonstrating possible neurotrauma-related AD, one pure CTE, and an example of a case exhibiting features of both AD and CTE. The future significance of this work lies not only in the confirmation of AD-CTE coexistence but more importantly, ways of generating a hypothesis about the possibility that CTE may accelerate AD development. Understanding the relationship between neurotrauma and neurodegenerative disease, will help elucidate how distinct disease entities can co-exist in the same patient. It will ultimately require the use of preclinical animal models and repeat injury paradigms to investigate clinically relevant injury mechanisms. These models should produce a CTE-like phenotype that must be both neuropathologically and behaviorally similar to human disease. Conclusion In this case series and review of the literature, we present a discussion of AD and CTE in the context of neurotrauma. We highlight recent work from repetitive neurotrauma models with an emphasis on those exhibiting a CTE-like phenotype. We briefly address potential mechanisms of interest shared amongst AD and CTE and advocate for future experiments to enhance understanding of CTE pathophysiology and the relationship between CTE and AD.

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Section: Discussionmentioning

confidence: 99%

Alzheimer’s disease and chronic traumatic encephalopathy: Distinct but possibly overlapping disease entities

et al. 2016

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“…The SH-SY5Y cell line has been widely used as an in vitro PD model [Alberio et al, 2010;Bauereis et al, 2011;Wang et al, 2014]. These cells express key markers of dopaminergic neurons like TH, DAT, VMAT2, Nurr1, and Pitx3.…”

Section: Discussionmentioning

confidence: 99%

Influence of 6‐Hydroxydopamine Toxicity on α‐Synuclein Phosphorylation, Resting Vesicle Expression, and Vesicular Dopamine Release

Ganapathy

Datta

Sowmithra

et al. 2016

J of Cellular Biochemistry

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Post mortem studies on familial and sporadic Parkinson's disease patient striatal tissue have shown that nearly 90% of α-synuclein deposited in Lewy-bodies is phosphorylated at serine-129 (pSyn-129) as opposed to only 4% in normal human brain. We aimed to find the influence of endogenous neurotoxin 6-hydroxydopamine (6-OHDA) on α-synuclein phosphorylation, resting vesicles, and vesicular dopamine release. The relative distribution of pSyn-129+ cells in apoptotic and non-apoptotic populations at different 6-OHDA concentrations was assessed along with changes in oxidant-antioxidant system, mitochondrial membrane-potential, and intracellular-Ca . Exposing SH-SY5Y cells to different concentrations of 6-OHDA for 48 h showed cell-death and apoptosis. Immunocytochemical analysis indicated an increase in pSyn-129 with increasing 6-OHDA concentration, and ELISA-estimation showed a significant increase in the pSyn-129 to α-synuclein ratio. FACS analysis also showed a significant increase in pSyn-129; and at sub-lethal 6-OHDA concentrations, pSyn-129+ cells were primarily distributed in the non-apoptotic population, suggesting that phosphorylation of α-synuclein precedes apoptosis. At higher 6-OHDA concentrations, the pSyn-129+ cell count significantly increased in the apoptotic population and decreased in the non-apoptotic population. Cytosolic co-localization of α-synuclein and ubiquitin was noticed at higher doses of 6-OHDA. FACS analysis showed decrease in vesicular monoamine transporter-2 (VMAT2) expression in 6-OHDA-treated cells, confirmed by reduction in functional dopamine-release on KCl and ATP stimulation. Significant decrease in VMAT2 expression and vesicular dopamine-release were observed with the lower 6-OHDA concentration, together with mild occurrence of apoptosis and significant increase in phosphorylated α-synuclein. This suggests that at sub-lethal 6-OHDA concentrations, the decrease in resting vesicles (VMAT2) and vesicular dopamine release are not attributable to apoptotic cell death and occur concomitantly with the phosphorylation of α-synuclein. J. Cell. Biochem. 117: 2719-2736, 2016. © 2016 Wiley Periodicals, Inc.

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“…89 Other sources of oxidative stress after TBI include NADPH oxidase, nitric oxide (NO) synthases, xanthine oxidase, and transition metals, which can be released by hemorrhage. 90,91 Underlying mechanisms of increased production of ROS by mitochondria include dysfunction of electron transport 92 and impairment in Ca 2þ buffering. 93 Mitochondria are also targets of ROS, which can promote MPTP opening, leading to apoptosis.…”

Section: Mitochondrial Failure After Traumatic Brain Injurymentioning

confidence: 99%

Emerging Therapies in Traumatic Brain Injury

et al. 2015

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Despite decades of basic and clinical research, treatments to improve outcomes after traumatic brain injury (TBI) are limited. However, based on the recent recognition of the prevalence of mild TBI, and its potential link to neurodegenerative disease, many new and exciting secondary injury mechanisms have been identified and several new therapies are being evaluated targeting both classic and novel paradigms. This includes a robust increase in both preclinical and clinical investigations. Using a mechanism-based approach the authors define the targets and emerging therapies for TBI. They address putative new therapies for TBI across both the spectrum of injury severity and the continuum of care, from the field to rehabilitation. They discuss TBI therapy using 11 categories, namely, (1) excitotoxicity and neuronal death, (2) brain edema, (3) mitochondria and oxidative stress, (4) axonal injury, (5) inflammation, (6) ischemia and cerebral blood flow dysregulation, (7) cognitive enhancement, (8) augmentation of endogenous neuroprotection, (9) cellular therapies, (10) combination therapy, and (11) TBI resuscitation. The current golden age of TBI research represents a special opportunity for the development of breakthroughs in the field.

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Mechanical stretch exacerbates the cell death in SH-SY5Y cells exposed to paraquat: mitochondrial dysfunction and oxidative stress

Cited by 32 publications

References 38 publications

Alzheimer’s disease and chronic traumatic encephalopathy: Distinct but possibly overlapping disease entities

Alzheimer’s disease and chronic traumatic encephalopathy: Distinct but possibly overlapping disease entities

Influence of 6‐Hydroxydopamine Toxicity on α‐Synuclein Phosphorylation, Resting Vesicle Expression, and Vesicular Dopamine Release

Emerging Therapies in Traumatic Brain Injury

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