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

Chaitra Venugopal, Y. S.Harish Chandra Prasad, K. Shobha, Venkata Bharatkumar Pinnelli, Anandh Dhanushkodi

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 μM) 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.

Original languageEnglish
Pages (from-to)189-200
Number of pages12
JournalNeuroToxicology
Volume69
DOIs
Publication statusPublished - 01-12-2018

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Kainic Acid
Somatomedins
Phosphatidylinositol 3-Kinases
Antioxidants
Scavenging
Free Radicals
Cells
Neurodegenerative diseases
Kainic Acid Receptors
HEK293 Cells
Poisons
Neuroprotective Agents
Cell- and Tissue-Based Therapy
Neurodegenerative Diseases
Neurons
Reactive Oxygen Species
Cell Survival
Intercellular Signaling Peptides and Proteins
Kidney
Therapeutics

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Toxicology

Cite this

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title = "HEK-293 secretome attenuates kainic acid neurotoxicity through insulin like growth factor-phosphatidylinositol-3-kinases pathway and by temporal regulation of antioxidant defense machineries",
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 μM) 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.",
author = "Chaitra Venugopal and Prasad, {Y. S.Harish Chandra} and K. Shobha and Pinnelli, {Venkata Bharatkumar} and Anandh Dhanushkodi",
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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; Prasad, Y. S.Harish Chandra; Shobha, K.; Pinnelli, Venkata Bharatkumar; Dhanushkodi, Anandh.

In: NeuroToxicology, Vol. 69, 01.12.2018, p. 189-200.

Research output: Contribution to journalArticle

TY - JOUR

T1 - HEK-293 secretome attenuates kainic acid neurotoxicity through insulin like growth factor-phosphatidylinositol-3-kinases pathway and by temporal regulation of antioxidant defense machineries

AU - Venugopal, Chaitra

AU - Prasad, Y. S.Harish Chandra

AU - Shobha, K.

AU - Pinnelli, Venkata Bharatkumar

AU - Dhanushkodi, Anandh

PY - 2018/12/1

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AB - 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 μM) 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.

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