Amyloid β Induces Early Changes in the Ribosomal Machinery, Cytoskeletal Organization and Oxidative Phosphorylation in Retinal Photoreceptor Cells

Liting Deng; Kanishka Pushpitha; Chitra Joseph; Veer Gupta; Rashi Rajput; Nitin Chitranshi; Yogita Dheer; Ardeshir Amirkhani; Ardeshir Amirkhani; Karthik Kamath; Karthik Kamath; Dana Pascovici; Dana Pascovici; Jemma X. Wu; Jemma X. Wu; Ghasem Hosseini Salekdeh; Ghasem Hosseini Salekdeh; Paul A. Haynes; Stuart L. Graham; Vivek K. Gupta; Mehdi Mirzaei; Mehdi Mirzaei; Mehdi Mirzaei

doi:10.3389/fnmol.2019.00024

Frontiers in Molecular Neuroscience (Feb 2019)

Amyloid β Induces Early Changes in the Ribosomal Machinery, Cytoskeletal Organization and Oxidative Phosphorylation in Retinal Photoreceptor Cells

Liting Deng,
Kanishka Pushpitha,
Chitra Joseph,
Veer Gupta,
Rashi Rajput,
Nitin Chitranshi,
Yogita Dheer,
Ardeshir Amirkhani,
Ardeshir Amirkhani,
Karthik Kamath,
Karthik Kamath,
Dana Pascovici,
Dana Pascovici,
Jemma X. Wu,
Jemma X. Wu,
Ghasem Hosseini Salekdeh,
Ghasem Hosseini Salekdeh,
Paul A. Haynes,
Stuart L. Graham,
Vivek K. Gupta,
Mehdi Mirzaei,
Mehdi Mirzaei,
Mehdi Mirzaei

Affiliations

Liting Deng: Department of Molecular Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, Australia
Kanishka Pushpitha: Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia
Chitra Joseph: Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia
Veer Gupta: School of Medicine, Deakin University, Waurn Ponds, VIC, Australia
Rashi Rajput: Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia
Nitin Chitranshi: Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia
Yogita Dheer: Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia
Ardeshir Amirkhani: Department of Molecular Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, Australia
Ardeshir Amirkhani: Australian Proteome Analysis Facility (APAF), Macquarie University, Sydney, NSW, Australia
Karthik Kamath: Department of Molecular Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, Australia
Karthik Kamath: Australian Proteome Analysis Facility (APAF), Macquarie University, Sydney, NSW, Australia
Dana Pascovici: Department of Molecular Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, Australia
Dana Pascovici: Australian Proteome Analysis Facility (APAF), Macquarie University, Sydney, NSW, Australia
Jemma X. Wu: Department of Molecular Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, Australia
Jemma X. Wu: Australian Proteome Analysis Facility (APAF), Macquarie University, Sydney, NSW, Australia
Ghasem Hosseini Salekdeh: Department of Molecular Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, Australia
Ghasem Hosseini Salekdeh: Cell Science Research Center, Department of Molecular Systems Biology, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran
Paul A. Haynes: Department of Molecular Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, Australia
Stuart L. Graham: Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia
Vivek K. Gupta: Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia
Mehdi Mirzaei: Department of Molecular Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, Australia
Mehdi Mirzaei: Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia
Mehdi Mirzaei: Australian Proteome Analysis Facility (APAF), Macquarie University, Sydney, NSW, Australia

DOI: https://doi.org/10.3389/fnmol.2019.00024
Journal volume & issue: Vol. 12

Abstract

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Amyloid β (Aβ) accumulation and its aggregation is characteristic molecular feature of the development of Alzheimer’s disease (AD). More recently, Aβ has been suggested to be associated with retinal pathology associated with AD, glaucoma and drusen deposits in age related macular degeneration (AMD). In this study, we investigated the proteins and biochemical networks that are affected by Aβ in the 661 W photoreceptor cells in culture. Time and dose dependent effects of Aβ on the photoreceptor cells were determined utilizing tandem mass tag (TMT) labeling-based quantitative mass-spectrometric approach. Bioinformatic analysis of the data revealed concentration and time dependent effects of the Aβ peptide stimulation on various key biochemical pathways that might be involved in mediating the toxicity effects of the peptide. We identified increased Tau phosphorylation, GSK3β dysregulation and reduced cell viability in cells treated with Aβ in a dose and time dependent manner. This study has delineated for the first-time molecular networks in photoreceptor cells that are impacted early upon Aβ treatment and contrasted the findings with a longer-term treatment effect. Proteins associated with ribosomal machinery homeostasis, mitochondrial function and cytoskeletal organization were affected in the initial stages of Aβ exposure, which may provide key insights into AD effects on the photoreceptors and specific molecular changes induced by Aβ peptide.

Published in Frontiers in Molecular Neuroscience

ISSN: 1662-5099 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.frontiersin.org/journals/molecular-neuroscience

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