Neuroprotective effect of whey protein hydrolysate containing leucine-aspartate-isoleucine-glutamine-lysine on HT22 cells in hydrogen peroxide–induced oxidative stress

ABSTRACT: This study aimed to investigate the neuroprotective effects of whey protein hydrolysate (WPH) containing the pentapeptide leucine-aspartate-isoleucine-glutamine-lysine (LDIQK). Whey protein hydrolysate (50, 100, and 200 µg/mL) demonstrated the ability to restore the viability of HT22 cells...

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Main Authors: Yeok B. Chang, Eun-Jin Jung, Kyungae Jo, Hyung J. Suh, Hyeon-Son Choi
Format: Article
Language:English
Published: Elsevier 2024-05-01
Series:Journal of Dairy Science
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022030223012158
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author Yeok B. Chang
Eun-Jin Jung
Kyungae Jo
Hyung J. Suh
Hyeon-Son Choi
author_facet Yeok B. Chang
Eun-Jin Jung
Kyungae Jo
Hyung J. Suh
Hyeon-Son Choi
author_sort Yeok B. Chang
collection DOAJ
description ABSTRACT: This study aimed to investigate the neuroprotective effects of whey protein hydrolysate (WPH) containing the pentapeptide leucine-aspartate-isoleucine-glutamine-lysine (LDIQK). Whey protein hydrolysate (50, 100, and 200 µg/mL) demonstrated the ability to restore the viability of HT22 cells subjected to 300 µM hydrogen peroxide (H2O2)-induced oxidative stress. Furthermore, at a concentration of 200 µg/mL, it significantly reduced the increase in reactive oxygen species production and calcium ion (Ca2+) influx induced by H2O2 by 46.1% and 46.2%, respectively. Similarly, the hydrolysate significantly decreased the levels of p-tau, a hallmark of tauopathy, and BCL2 associated X (BAX), a proapoptosis factor, while increasing the protein levels of choline acetyltransferase (ChAT), an enzyme involved in acetylcholine synthesis, brain-derived neurotrophic factor (BDNF), a nerve growth factor, and B-cell lymphoma 2 (BCL2, an antiapoptotic factor. Furthermore, it increased nuclear factor erythroid 2-related factor 2 (Nrf2)-hemoxygenase-1(HO-1) signaling, which is associated with the antioxidant response, while reducing the activation of mitogen-activated protein kinase (MAPK) signaling pathway components, namely phosphor-extracellular signal-regulated kinases (p-ERK), phosphor-c-Jun N-terminal kinases (p-JNK), and p-p38. Column chromatography and tandem mass spectrometry analysis identified LDIQK as a compound with neuroprotective effects in WPH; it inhibited Ca2+ influx and regulated the BAX/BCL2 ratio. Collectively, WPH containing LDIQK demonstrated neuroprotective effects against H2O2-induced neuronal cell damage, suggesting that WPH or its active peptide, LDIQK, may serve as a potential edible agent for improving cognitive dysfunction.
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spelling doaj.art-ac695123e000426ea8e02c17bdb58c3c2024-04-19T04:16:15ZengElsevierJournal of Dairy Science0022-03022024-05-01107526202632Neuroprotective effect of whey protein hydrolysate containing leucine-aspartate-isoleucine-glutamine-lysine on HT22 cells in hydrogen peroxide–induced oxidative stressYeok B. Chang0Eun-Jin Jung1Kyungae Jo2Hyung J. Suh3Hyeon-Son Choi4Department of Integrated Biomedical and Life Science, Graduate School, Korea University, Seoul 02841, Republic of Korea; Transdisciplinary Major in Learning Health Systems, Graduate School, Korea University, Seoul 02841, Republic of KoreaDepartment of Food and Biotechnology, Korea University, Sejong 30019, Republic of KoreaDepartment of Integrated Biomedical and Life Science, Graduate School, Korea University, Seoul 02841, Republic of KoreaDepartment of Integrated Biomedical and Life Science, Graduate School, Korea University, Seoul 02841, Republic of Korea; Transdisciplinary Major in Learning Health Systems, Graduate School, Korea University, Seoul 02841, Republic of Korea; Corresponding authorsDepartment of Food Nutrition, Sangmyung University, Seoul 03016, Republic of Korea; Corresponding authorsABSTRACT: This study aimed to investigate the neuroprotective effects of whey protein hydrolysate (WPH) containing the pentapeptide leucine-aspartate-isoleucine-glutamine-lysine (LDIQK). Whey protein hydrolysate (50, 100, and 200 µg/mL) demonstrated the ability to restore the viability of HT22 cells subjected to 300 µM hydrogen peroxide (H2O2)-induced oxidative stress. Furthermore, at a concentration of 200 µg/mL, it significantly reduced the increase in reactive oxygen species production and calcium ion (Ca2+) influx induced by H2O2 by 46.1% and 46.2%, respectively. Similarly, the hydrolysate significantly decreased the levels of p-tau, a hallmark of tauopathy, and BCL2 associated X (BAX), a proapoptosis factor, while increasing the protein levels of choline acetyltransferase (ChAT), an enzyme involved in acetylcholine synthesis, brain-derived neurotrophic factor (BDNF), a nerve growth factor, and B-cell lymphoma 2 (BCL2, an antiapoptotic factor. Furthermore, it increased nuclear factor erythroid 2-related factor 2 (Nrf2)-hemoxygenase-1(HO-1) signaling, which is associated with the antioxidant response, while reducing the activation of mitogen-activated protein kinase (MAPK) signaling pathway components, namely phosphor-extracellular signal-regulated kinases (p-ERK), phosphor-c-Jun N-terminal kinases (p-JNK), and p-p38. Column chromatography and tandem mass spectrometry analysis identified LDIQK as a compound with neuroprotective effects in WPH; it inhibited Ca2+ influx and regulated the BAX/BCL2 ratio. Collectively, WPH containing LDIQK demonstrated neuroprotective effects against H2O2-induced neuronal cell damage, suggesting that WPH or its active peptide, LDIQK, may serve as a potential edible agent for improving cognitive dysfunction.http://www.sciencedirect.com/science/article/pii/S0022030223012158whey protein hydrolysateLDIQKneuroprotective effectHT22 celloxidative stress
spellingShingle Yeok B. Chang
Eun-Jin Jung
Kyungae Jo
Hyung J. Suh
Hyeon-Son Choi
Neuroprotective effect of whey protein hydrolysate containing leucine-aspartate-isoleucine-glutamine-lysine on HT22 cells in hydrogen peroxide–induced oxidative stress
Journal of Dairy Science
whey protein hydrolysate
LDIQK
neuroprotective effect
HT22 cell
oxidative stress
title Neuroprotective effect of whey protein hydrolysate containing leucine-aspartate-isoleucine-glutamine-lysine on HT22 cells in hydrogen peroxide–induced oxidative stress
title_full Neuroprotective effect of whey protein hydrolysate containing leucine-aspartate-isoleucine-glutamine-lysine on HT22 cells in hydrogen peroxide–induced oxidative stress
title_fullStr Neuroprotective effect of whey protein hydrolysate containing leucine-aspartate-isoleucine-glutamine-lysine on HT22 cells in hydrogen peroxide–induced oxidative stress
title_full_unstemmed Neuroprotective effect of whey protein hydrolysate containing leucine-aspartate-isoleucine-glutamine-lysine on HT22 cells in hydrogen peroxide–induced oxidative stress
title_short Neuroprotective effect of whey protein hydrolysate containing leucine-aspartate-isoleucine-glutamine-lysine on HT22 cells in hydrogen peroxide–induced oxidative stress
title_sort neuroprotective effect of whey protein hydrolysate containing leucine aspartate isoleucine glutamine lysine on ht22 cells in hydrogen peroxide induced oxidative stress
topic whey protein hydrolysate
LDIQK
neuroprotective effect
HT22 cell
oxidative stress
url http://www.sciencedirect.com/science/article/pii/S0022030223012158
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