Role of lycopene in mitochondrial protection during differential levels of oxidative stress in primary cortical neurons

Park, Hana; Stumpf, Allison; Broman, Katheryn; Jansen, Joseph; Dunn, Tracie; Scott, Madison; Crowe-White, Kristi

doi:10.1016/j.dscb.2021.100016

Cited by 7 publications

(6 citation statements)

References 48 publications

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“…By activating the ARE transcription pathway [ 26 ], lycopene can affect xenobiotic metabolism by disrupting the cytosolic linkages between the major ARE-activating Nrf2 and its inhibitor (Keap1) [ 26 , 102 ]. Once liberated of Keap1, Nrf2 translocates to the nucleus, where it induces phase II enzyme expression [ 26 , 103 ]. According to some research, overexpression of phase II detoxification enzymes, in addition to blocking phase I metabolism and metabolic activation of aflatoxin B1, enhances lycopene’s anti-aflatoxin actions [ 104 , 105 ].…”

Section: Lycopene As An Antioxidantmentioning

confidence: 99%

Lycopene: A Natural Arsenal in the War against Oxidative Stress and Cardiovascular Diseases

et al. 2022

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Lycopene is a bioactive red pigment found in plants, especially in red fruits and vegetables, including tomato, pink guava, papaya, pink grapefruit, and watermelon. Several research reports have advocated its positive impact on human health and physiology. For humans, lycopene is an essential substance obtained from dietary sources to fulfil the body requirements. The production of reactive oxygen species (ROS) causing oxidative stress and downstream complications include one of the major health concerns worldwide. In recent years, oxidative stress and its counter strategies have attracted biomedical research in order to manage the emerging health issues. Lycopene has been reported to directly interact with ROS, which can help to prevent chronic diseases, including diabetes and neurodegenerative and cardiovascular diseases. In this context, the present review article was written to provide an accumulative account of protective and ameliorative effects of lycopene on coronary artery disease (CAD) and hypertension, which are the leading causes of death worldwide. Lycopene is a potent antioxidant that fights ROS and, subsequently, complications. It reduces blood pressure via inhibiting the angiotensin-converting enzyme and regulating nitrous oxide bioavailability. It plays an important role in lowering of LDL (low-density lipoproteins) and improving HDL (high-density lipoproteins) levels to minimize atherosclerosis, which protects the onset of coronary artery disease and hypertension. Various studies have advocated that lycopene exhibited a combating competence in the treatment of these diseases. Owing to all the antioxidant, anti-diabetic, and anti-hypertensive properties, lycopene provides a potential nutraceutical with a protective and curing ability against coronary artery disease and hypertension.

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Section: Lycopene As An Antioxidantmentioning

confidence: 99%

Lycopene: A Natural Arsenal in the War against Oxidative Stress and Cardiovascular Diseases

et al. 2022

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“…Primary rat cortical and dopaminergic neurons were prepared from rat feti (Sprague–Dawley, day 18 of gestation; Envigo, Indianapolis, IN) as described previously ( 94 ). Briefly, neurons (0.5 × 10 6 cells/ 35 mm plate) were grown in neurobasal medium supplemented with B-27, glutamine, and antibiotics (Thermo Fisher Scientific, Waltham, MA, USA) for 12 d in vitro.…”

Section: Methodsmentioning

confidence: 99%

Integrated regulation of dopaminergic and epigenetic effectors of neuroprotection in Parkinson’s disease models

Nourse

Russell

Moniz

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Whole-exome sequencing of Parkinson’s disease (PD) patient DNA identified single-nucleotide polymorphisms (SNPs) in the tyrosine nonreceptor kinase-2 ( TNK2 ) gene. Although this kinase had a previously demonstrated activity in preventing the endocytosis of the dopamine reuptake transporter (DAT), a causal role for TNK2-associated dysfunction in PD remains unresolved. We postulated the dopaminergic neurodegeneration resulting from patient-associated variants in TNK2 were a consequence of aberrant or prolonged TNK2 overactivity, the latter being a failure in TNK2 degradation by an E3 ubiquitin ligase, neuronal precursor cell-expressed developmentally down-regulated-4 (NEDD4). Interestingly, systemic RNA interference protein-3 (SID-3) is the sole TNK2 ortholog in the nematode Caenorhabditis elegans , where it is an established effector of epigenetic gene silencing mediated through the dsRNA-transporter, SID-1. We hypothesized that TNK2/SID-3 represents a node of integrated dopaminergic and epigenetic signaling essential to neuronal homeostasis. Use of a TNK2 inhibitor (AIM-100) or a NEDD4 activator [N-aryl benzimidazole 2 (NAB2)] in bioassays for either dopamine- or dsRNA-uptake into worm dopaminergic neurons revealed that sid-3 mutants displayed robust neuroprotection from 6-hydroxydopamine (6-OHDA) exposures, as did AIM-100 or NAB2-treated wild-type animals. Furthermore, NEDD4 activation by NAB2 in rat primary neurons correlated to a reduction in TNK2 levels and the attenuation of 6-OHDA neurotoxicity. CRISPR-edited nematodes engineered to endogenously express SID-3 variants analogous to TNK2 PD-associated SNPs exhibited enhanced susceptibility to dopaminergic neurodegeneration and circumvented the RNAi resistance characteristic of SID-3 dysfunction. This research exemplifies a molecular etiology for PD whereby dopaminergic and epigenetic signaling are coordinately regulated to confer susceptibility or resilience to neurodegeneration.

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“…Primary rat cortical and dopaminergic neurons were prepared from rat feti (Sprague-Dawley, day 18 of gestation; Envigo, Indianapolis, IN) as described previously (91). Briefly, neurons (0.5 × 10 6 cells/ 35mm plate) were grown in neurobasal medium supplemented with B-27, glutamine, and antibiotics (Thermo Fisher Scientific, Waltham, MA, USA) for 12 days in vitro.…”

Section: Methodsmentioning

confidence: 99%

Integrated Regulation of Dopaminergic and Epigenetic Effectors of Neuroprotection in Parkinson’s Disease Models

Nourse

Russell

Moniz

et al. 2022

Preprint

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Whole exome sequencing of Parkinson's disease (PD) patient DNA identified single-nucleotide polymorphisms (SNPs) in the TNK2 gene. Although TNK2 encodes a non-receptor tyrosine kinase that has been shown to prevent the endocytosis of the dopamine reuptake transporter (DAT), a causal role for TNK2 in PD remains unresolved. We postulated that specific recessive mutations in patients resulted in aberrant or prolonged overactivity as a consequence of failed negative regulation by an E3 ubiquitin ligase, NEDD4. Interestingly, the sole Caenorhabditis elegans ortholog of TNK2, termed SID-3, is an established mediator of epigenetic gene silencing and systemic RNA interference facilitated by the SID-1 dsRNA transporter. While SID-3 had no prior association to dopamine neurotransmission in C. elegans, we hypothesized that TNK2/SID-3 represented a node of integrated dopaminergic and epigenetic signaling essential to neuronal homeostasis. Using genetic and chemical modifiers, including a TNK2 inhibitor (AIM-100) and NEDD4 activator (NAB2), in bioassays for dopamine uptake or RNAi in dopaminergic neurons of C. elegans, we determined that sid-3 mutants displayed neuroprotection from 6-hydroxydopamine (6-OHDA) exposure, as did wildtype animals treated with AIM-100 or NAB2. Additionally, NAB2 treatment of rat primary neurons correlated with a reduction of TNK2 levels and the attenuation of 6-OHDA neurotoxicity. Notably, CRISPR-modified nematodes engineered with genomic mutations in sid-3 analogous to PD patient-associated SNPs in TNK2 circumvented the resistance to RNAi characteristic of SID-3 dysfunction and furthermore exhibited enhanced susceptibility to neurodegeneration. This study describes a molecular etiology for PD whereby dysfunctional cellular dynamics, dopaminergic, and epigenetic signaling intersect to cause neurodegeneration.

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Role of lycopene in mitochondrial protection during differential levels of oxidative stress in primary cortical neurons

Cited by 7 publications

References 48 publications

Lycopene: A Natural Arsenal in the War against Oxidative Stress and Cardiovascular Diseases

Lycopene: A Natural Arsenal in the War against Oxidative Stress and Cardiovascular Diseases

Integrated regulation of dopaminergic and epigenetic effectors of neuroprotection in Parkinson’s disease models

Integrated Regulation of Dopaminergic and Epigenetic Effectors of Neuroprotection in Parkinson’s Disease Models

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