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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Elsevier
2024-05-01
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Series: | Journal of Dairy Science |
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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. |
first_indexed | 2024-04-24T07:44:50Z |
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issn | 0022-0302 |
language | English |
last_indexed | 2024-04-24T07:44:50Z |
publishDate | 2024-05-01 |
publisher | Elsevier |
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series | Journal of Dairy Science |
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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