Haptoglobin increases with age in rat hippocampus and modulates Apolipoprotein E mediated cholesterol trafficking in neuroblastoma cell lines

Spagnuolo, Maria Stefania; Maresca, Bernardetta; Mollica, Maria Pina; Cavaliere, Gina; Cefaliello, Carolina; Trinchese, Giovanna; Esposito, Maria; Scudiero, Rosaria; Crispino, Marianna; Abrescia, Paolo; Cigliano, Luisa

doi:10.3389/fncel.2014.00212

Cited by 27 publications

(32 citation statements)

References 59 publications

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“…These properties of trehalose make it a promising compound for reducing protein aggregates that contribute to aging and aging-related diseases. Hp has been proposed as an aging biomarker in mouse (Ding and Kopchick 2011) and has also been shown to increase with age in rat hippocampus (Spagnuolo et al 2014b). In humans, high levels of Hp in older adults have been observed in some studies (Miura et al 2011;Shamsi et al 2012) but not in others (Byerley et al 2010;Napolioni et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Increased levels of hyper-stable protein aggregates in plasma of older adults

Xia

Trasatti

Wymer

et al. 2016

AGE

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Proteins that misfold into hyper-stable/degradation-resistant species during aging may accumulate and disrupt protein homeostasis (i.e., proteostasis), thereby posing a survival risk to any organism. Using the method diagonal two-dimensional (D2D) SDS-PAGE, which separates hyper-stable SDS-resistant proteins at a proteomics level, we analyzed the plasma of healthy young (<30 years) and older (60-80 years) adults. We discovered the presence of soluble SDSresistant protein aggregates in the plasma of older adults, but found significantly lower levels in the plasma of young adults. We identified the inflammation-related chaperone protein haptoglobin as the main component of the hyper-stable aggregates. This observation is consistent with the growing link between accumulations of protein aggregates and aging across many organisms. It is plausible higher amounts of SDS-resistant protein aggregates in the plasma of older adults may reflect a compromise in proteostasis that may potentially indicate cellular aging and/or disease risk. The results of this study have implications for further understanding the link between aging and the accumulation of protein aggregates, as well as potential for the development of aging-related biomarkers. More broadly, this novel application of D2D SDS-PAGE may be used to identify, quantify, and characterize the degradation-resistant protein aggregates in human plasma or any biological system.

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Section: Discussionmentioning

confidence: 99%

Increased levels of hyper-stable protein aggregates in plasma of older adults

Xia

Trasatti

Wymer

et al. 2016

AGE

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“…Proteins were extracted from hippocampus and frontal cortex by homogenizing aliquots (about 40 mg) of frozen tissues in six volumes (w/v) of cold buffer, as previously published [58]. Homogenates were centrifuged (14,000× g, 45 min, 4 • C), and supernatants were then collected.…”

Section: Western Blottingmentioning

confidence: 99%

Adipose Tissue and Brain Metabolic Responses to Western Diet—Is There a Similarity between the Two?

Mazzoli

Spagnuolo

Gatto

et al. 2020

IJMS

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Dietary fats and sugars were identified as risk factors for overweight and neurodegeneration, especially in middle-age, an earlier stage of the aging process. Therefore, our aim was to study the metabolic response of both white adipose tissue and brain in middle aged rats fed a typical Western diet (high in saturated fats and fructose, HFF) and verify whether a similarity exists between the two tissues. Specific cyto/adipokines (tumor necrosis factor alpha (TNF-α), adiponectin), critical obesity-inflammatory markers (haptoglobin, lipocalin), and insulin signaling or survival protein network (insulin receptor substrate 1 (IRS), Akt, Erk) were quantified in epididymal white adipose tissue (e-WAT), hippocampus, and frontal cortex. We found a significant increase of TNF-α in both e-WAT and hippocampus of HFF rats, while the expression of haptoglobin and lipocalin was differently affected in the various tissues. Interestingly, adiponectin amount was found significantly reduced in e-WAT, hippocampus, and frontal cortex of HFF rats. Insulin signaling was impaired by HFF diet in e-WAT but not in brain. The above changes were associated with the decrease in brain derived neurotrophic factor (BDNF) and synaptotagmin I and the increase in post-synaptic protein PSD-95 in HFF rats. Overall, our investigation supports for the first time similarities in the response of adipose tissue and brain to Western diet.

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“…Also, cholesterol treatment reduced cell viability in SH-SY5Y cells in dose-dependent manner [26]. Literature reveals potential adverse impact of cholesterol in neurodegenerative diseases, and the fact that accumulation of non-esterified cholesterol, which predominates in CNS, regulates the cholesterol homeostasis and is toxic to neuronal cells [27-30].…”

Section: Discussionmentioning

confidence: 99%

1-Methyl-4-Phenylpyridinium-Induced Death of Differentiated SH-SY5Y Neurons Is Potentiated by Cholesterol

Raju¹,

Jaisankar

Borah

et al. 2017

Ann Neurosci

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Background/Aims: Hypercholesterolemia is recently considered a risk factor for Parkinson’s disease (PD), the most consistent neurodegenerative movement disorder. The study aimed to investigate the effect of exogenous cholesterol on 1-methyl-4-phenylpyridinium (MPP⁺) parkinsonian neurotoxin-induced cell death, loss of mitochondrial membrane potential, and dopaminergic deficiency in a cellular model of PD. Methods: Cholesterol (50 μM) when added in the culture media alone or in combination with MPP⁺ was studied in SH-SY5Y neuroblastoma cells. There were 4 groups that were studied; SH-SY5Y cells treated with vehicle (control), cells that were treated with 1 mM MPP⁺ (MPP⁺), or cholesterol (chol) or both (M + chol). The loss of cell survival was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Dopamine depletion, microtubule-associated protein 2 (MAP-2), and tyrosine hydroxylase (TH)-positive neuronal loss were determined by HPLC-electrochemical detection and TH immunocytochemistry respectively. Mitochondrial membrane potential in cells stained by tetramethylrhodamine methyl ester dye was analysed by flow cytometry. Results: Cholesterol treatment potentiated a reduction of neuronal viability with loss of TH-positive neurons in cultures. MPP⁺-induced depletion of dopamine level in the post-mitotic MAP-2 immunoreactive neurons and loss of mitochondrial membrane potential were also heightened by cholesterol. Conclusion: Apparently, changes in neuronal cholesterol content significantly influenced the neurotoxicity and the direct mitochondrial mechanisms involved in MPP⁺-induced cell death. Our observations demonstrate that high cholesterol incorporated into the differentiated human neuroblastoma cells worsened dopaminergic neuronal survivability through increased depolarization of mitochondrial membrane potential, which is a known mechanism of dopaminergic cell death by MPP⁺. The present findings support the hypothesis that hypercholesterolemia could be a risk factor for PD.

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Haptoglobin increases with age in rat hippocampus and modulates Apolipoprotein E mediated cholesterol trafficking in neuroblastoma cell lines

Cited by 27 publications

References 59 publications

Increased levels of hyper-stable protein aggregates in plasma of older adults

Increased levels of hyper-stable protein aggregates in plasma of older adults

Adipose Tissue and Brain Metabolic Responses to Western Diet—Is There a Similarity between the Two?

1-Methyl-4-Phenylpyridinium-Induced Death of Differentiated SH-SY5Y Neurons Is Potentiated by Cholesterol

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