HEK-293 secretome attenuates kainic acid neurotoxicity through insulin like growth factor-phosphatidylinositol-3-kinases pathway and by temporal regulation of antioxidant defense machineries

Venugopal, Chaitra and Harish Chandra Prasad, YS and Shobha, K and Dhanushkodi, Anandh (2018) HEK-293 secretome attenuates kainic acid neurotoxicity through insulin like growth factor-phosphatidylinositol-3-kinases pathway and by temporal regulation of antioxidant defense machineries. NeuroToxicology, 69. pp. 189-200. ISSN 0161-813X

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Abstract

A major impediment in the success of cell therapy for neurodegenerative diseases is the poor survival of grafted cells in the in vivo milieu, predominantly due to accumulated reactive oxygen species, thus prompting the search for suitable alternatives. Accumulating evidence suggests that the therapeutic potential of transplanted cells is partially attributed to the secretome released by them into the extracellular milieu. Studies that investigated the neuroprotective potential of the secretome attributes to the mere presence of growth factors without addressing other underlying cellular/molecular changes that occur upon post-secretome intervention like re-establishing the host cell’s free radical scavenging machineries. In the present study, we investigated the neuroprotective effects of human embryonic kidney (HEK-293) cell line derived secretome (HEK-S) in an in vitro model of kainic acid (KA) induced neurodegeneration and explored the possible neuroprotective mechanism(s) of HEK-S. Murine hippocampal cells were exposed to toxic doses of KA (200 mM) for 6 hours (H) or 24H to induce excitotoxicity. Kainic acid exposed hippocampal cells were then treated with HEK-S either simultaneously or 6 h post-KA exposure. Our results revealed that HEK-S confers significant neuroprotection in early/later stages of neurodegeneration through insulin like growth factor (IGF) – phosphatidylinositol-3-kinases (PI3 K) pathway, efficiently restoring the host’s free radical scavenging mechanisms at molecular-cellular-biochemical levels and also by modulating kainate receptor subunit expressions in host neurons

Item Type: Article
Uncontrolled Keywords: Neurodegeneration; Neuroprotection; Antioxidant; Oxidative stress; Free radicals; Secretome
Subjects: Regenerative Medicine > MIRM Bangalore
Depositing User: MCON Library
Date Deposited: 17 Apr 2019 03:38
Last Modified: 17 Apr 2019 03:38
URI: http://eprints.manipal.edu/id/eprint/152315

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