Diesel combustion is the major source of fine particle road emission, whose solid fraction is represented by diesel exhaust particles (DEP). Many studies indicate the contribution of DEP to the onset of different neurological diseases, such as Alzheimer's disease (AD), identifying oxidative stress and neuroinflammation as two cardinal processes of brain damage. This study aimed to investigate the effects of different concentrations of DEP (10 μg/ml and 50 μg/ml) on the mouse HT22 cells treated for 3 h or 24 h. Our results demonstrated that DEP contributed to an increased oxidative stress, defined by overexpression of HO-1, Hsp70 and Cyp1b1 protein levels. Moreover, an inflammatory-related processes were also observed, as COX-2 and iNOS levels were higher in treated cells when compared to the control. Furthermore, our investigations highlighted the alteration of fatty acid composition, total cholesterol content in cells and media, and of membrane fluidity, suggesting a lipid reshaping after DEP treatment. Finally, we detected APP and BACE1 increase after 24 h of treatment with 50 μg/ml of DEP. Indeed, our results propose a role of acute exposure in the onset of a deleterious mechanism for AD neurodegeneration, even though no differences were observed in p-APPThr668levels, BACE1 activity and APP C-terminal fragment beta amount.

Early evidence of stress in immortalized neurons exposed to diesel particles: the role of lipid reshaping behind oxidative stress and inflammation / C. Milani, P.A. Corsetto, F. Farina, L. Botto, E. Lonati, L. Massimino, A.M. Rizzo, A. Bulbarelli, P. Palestini. - In: TOXICOLOGY. - ISSN 0300-483X. - 409(2018 Nov), pp. 63-72. [10.1016/j.tox.2018.07.017]

Early evidence of stress in immortalized neurons exposed to diesel particles: the role of lipid reshaping behind oxidative stress and inflammation

P.A. Corsetto
Secondo
;
A.M. Rizzo;
2018

Abstract

Diesel combustion is the major source of fine particle road emission, whose solid fraction is represented by diesel exhaust particles (DEP). Many studies indicate the contribution of DEP to the onset of different neurological diseases, such as Alzheimer's disease (AD), identifying oxidative stress and neuroinflammation as two cardinal processes of brain damage. This study aimed to investigate the effects of different concentrations of DEP (10 μg/ml and 50 μg/ml) on the mouse HT22 cells treated for 3 h or 24 h. Our results demonstrated that DEP contributed to an increased oxidative stress, defined by overexpression of HO-1, Hsp70 and Cyp1b1 protein levels. Moreover, an inflammatory-related processes were also observed, as COX-2 and iNOS levels were higher in treated cells when compared to the control. Furthermore, our investigations highlighted the alteration of fatty acid composition, total cholesterol content in cells and media, and of membrane fluidity, suggesting a lipid reshaping after DEP treatment. Finally, we detected APP and BACE1 increase after 24 h of treatment with 50 μg/ml of DEP. Indeed, our results propose a role of acute exposure in the onset of a deleterious mechanism for AD neurodegeneration, even though no differences were observed in p-APPThr668levels, BACE1 activity and APP C-terminal fragment beta amount.
Amyloid Precursor Protein; Diesel exhaust particles; HT22 cells; Inflammation; Lipid reshaping; Oxidative stress; Toxicology
Settore BIO/10 - Biochimica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/585977
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