Role of Myeloperoxidase Oxidants in the Modulation of Cellular Lysosomal Enzyme Function: A Contributing Factor to Macrophage Dysfunction in Atherosclerosis?

Research output: Contribution to journalJournal articleResearchpeer-review

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Role of Myeloperoxidase Oxidants in the Modulation of Cellular Lysosomal Enzyme Function : A Contributing Factor to Macrophage Dysfunction in Atherosclerosis? / Ismael, Fahd O; Barrett, Tessa J; Sheipouri, Diba; Brown, Bronwyn E; Davies, Michael J; Hawkins, Clare Louise.

In: P L o S One, Vol. 11, No. 12, e0168844, 2016.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Ismael, FO, Barrett, TJ, Sheipouri, D, Brown, BE, Davies, MJ & Hawkins, CL 2016, 'Role of Myeloperoxidase Oxidants in the Modulation of Cellular Lysosomal Enzyme Function: A Contributing Factor to Macrophage Dysfunction in Atherosclerosis?', P L o S One, vol. 11, no. 12, e0168844. https://doi.org/10.1371/journal.pone.0168844

APA

Ismael, F. O., Barrett, T. J., Sheipouri, D., Brown, B. E., Davies, M. J., & Hawkins, C. L. (2016). Role of Myeloperoxidase Oxidants in the Modulation of Cellular Lysosomal Enzyme Function: A Contributing Factor to Macrophage Dysfunction in Atherosclerosis? P L o S One, 11(12), [e0168844]. https://doi.org/10.1371/journal.pone.0168844

Vancouver

Ismael FO, Barrett TJ, Sheipouri D, Brown BE, Davies MJ, Hawkins CL. Role of Myeloperoxidase Oxidants in the Modulation of Cellular Lysosomal Enzyme Function: A Contributing Factor to Macrophage Dysfunction in Atherosclerosis? P L o S One. 2016;11(12). e0168844. https://doi.org/10.1371/journal.pone.0168844

Author

Ismael, Fahd O ; Barrett, Tessa J ; Sheipouri, Diba ; Brown, Bronwyn E ; Davies, Michael J ; Hawkins, Clare Louise. / Role of Myeloperoxidase Oxidants in the Modulation of Cellular Lysosomal Enzyme Function : A Contributing Factor to Macrophage Dysfunction in Atherosclerosis?. In: P L o S One. 2016 ; Vol. 11, No. 12.

Bibtex

@article{90102ffaa63040849b6ad6a876b45b24,
title = "Role of Myeloperoxidase Oxidants in the Modulation of Cellular Lysosomal Enzyme Function: A Contributing Factor to Macrophage Dysfunction in Atherosclerosis?",
abstract = "Low-density lipoprotein (LDL) is the major source of lipid within atherosclerotic lesions. Myeloperoxidase (MPO) is present in lesions and forms the reactive oxidants hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN). These oxidants modify LDL and have been strongly linked with the development of atherosclerosis. In this study, we examined the effect of HOCl, HOSCN and LDL pre-treated with these oxidants on the function of lysosomal enzymes responsible for protein catabolism and lipid hydrolysis in murine macrophage-like J774A.1 cells. In each case, the cells were exposed to HOCl or HOSCN or LDL pre-treated with these oxidants. Lysosomal cathepsin (B, L and D) and acid lipase activities were quantified, with cathepsin and LAMP-1 protein levels determined by Western blotting. Exposure of J774A.1 cells to HOCl or HOSCN resulted in a significant decrease in the activity of the Cys-dependent cathepsins B and L, but not the Asp-dependent cathepsin D. Cathepsins B and L were also inhibited in macrophages exposed to HOSCN-modified, and to a lesser extent, HOCl-modified LDL. No change was seen in cathepsin D activity or the expression of the cathepsin proteins or lysosomal marker protein LAMP-1. The activity of lysosomal acid lipase was also decreased on treatment of macrophages with each modified LDL. Taken together, these results suggest that HOCl, HOSCN and LDL modified by these oxidants could contribute to lysosomal dysfunction and thus perturb the cellular processing of LDL, which could be important during the development of atherosclerosis.",
author = "Ismael, {Fahd O} and Barrett, {Tessa J} and Diba Sheipouri and Brown, {Bronwyn E} and Davies, {Michael J} and Hawkins, {Clare Louise}",
year = "2016",
doi = "10.1371/journal.pone.0168844",
language = "English",
volume = "11",
journal = "P L o S One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

RIS

TY - JOUR

T1 - Role of Myeloperoxidase Oxidants in the Modulation of Cellular Lysosomal Enzyme Function

T2 - A Contributing Factor to Macrophage Dysfunction in Atherosclerosis?

AU - Ismael, Fahd O

AU - Barrett, Tessa J

AU - Sheipouri, Diba

AU - Brown, Bronwyn E

AU - Davies, Michael J

AU - Hawkins, Clare Louise

PY - 2016

Y1 - 2016

N2 - Low-density lipoprotein (LDL) is the major source of lipid within atherosclerotic lesions. Myeloperoxidase (MPO) is present in lesions and forms the reactive oxidants hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN). These oxidants modify LDL and have been strongly linked with the development of atherosclerosis. In this study, we examined the effect of HOCl, HOSCN and LDL pre-treated with these oxidants on the function of lysosomal enzymes responsible for protein catabolism and lipid hydrolysis in murine macrophage-like J774A.1 cells. In each case, the cells were exposed to HOCl or HOSCN or LDL pre-treated with these oxidants. Lysosomal cathepsin (B, L and D) and acid lipase activities were quantified, with cathepsin and LAMP-1 protein levels determined by Western blotting. Exposure of J774A.1 cells to HOCl or HOSCN resulted in a significant decrease in the activity of the Cys-dependent cathepsins B and L, but not the Asp-dependent cathepsin D. Cathepsins B and L were also inhibited in macrophages exposed to HOSCN-modified, and to a lesser extent, HOCl-modified LDL. No change was seen in cathepsin D activity or the expression of the cathepsin proteins or lysosomal marker protein LAMP-1. The activity of lysosomal acid lipase was also decreased on treatment of macrophages with each modified LDL. Taken together, these results suggest that HOCl, HOSCN and LDL modified by these oxidants could contribute to lysosomal dysfunction and thus perturb the cellular processing of LDL, which could be important during the development of atherosclerosis.

AB - Low-density lipoprotein (LDL) is the major source of lipid within atherosclerotic lesions. Myeloperoxidase (MPO) is present in lesions and forms the reactive oxidants hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN). These oxidants modify LDL and have been strongly linked with the development of atherosclerosis. In this study, we examined the effect of HOCl, HOSCN and LDL pre-treated with these oxidants on the function of lysosomal enzymes responsible for protein catabolism and lipid hydrolysis in murine macrophage-like J774A.1 cells. In each case, the cells were exposed to HOCl or HOSCN or LDL pre-treated with these oxidants. Lysosomal cathepsin (B, L and D) and acid lipase activities were quantified, with cathepsin and LAMP-1 protein levels determined by Western blotting. Exposure of J774A.1 cells to HOCl or HOSCN resulted in a significant decrease in the activity of the Cys-dependent cathepsins B and L, but not the Asp-dependent cathepsin D. Cathepsins B and L were also inhibited in macrophages exposed to HOSCN-modified, and to a lesser extent, HOCl-modified LDL. No change was seen in cathepsin D activity or the expression of the cathepsin proteins or lysosomal marker protein LAMP-1. The activity of lysosomal acid lipase was also decreased on treatment of macrophages with each modified LDL. Taken together, these results suggest that HOCl, HOSCN and LDL modified by these oxidants could contribute to lysosomal dysfunction and thus perturb the cellular processing of LDL, which could be important during the development of atherosclerosis.

U2 - 10.1371/journal.pone.0168844

DO - 10.1371/journal.pone.0168844

M3 - Journal article

C2 - 27997605

VL - 11

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 12

M1 - e0168844

ER -

ID: 172849682