Adaptive responses of neuronal cells to chronic endoplasmic reticulum (ER) stress
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved..
Accumulation of misfolded proteins or perturbation of calcium homeostasis leads to endoplasmic reticulum (ER) stress and is linked to the pathogenesis of neurodegenerative diseases. Hence, understanding the ability of neuronal cells to cope with chronic ER stress is of fundamental interest. Interestingly, several brain areas uphold functions that enable them to resist challenges associated with neurodegeneration. Here, we established novel clonal mouse hippocampal (HT22) cell lines that are resistant to prolonged (chronic) ER stress induced by thapsigargin (TgR) or tunicamycin (TmR) as in vitro models to study the adaption to ER stress. Morphologically, we observed a significant increase in vesicular und autophagosomal structures in both resistant lines and 'giant lysosomes', especially striking in TgR cells. While autophagic activity increased under ER stress, lysosomal function appeared slightly impaired; in both cell lines, we observed enhanced ER-phagy. However, proteomic analyses revealed that various protein clusters and signaling pathways were differentially regulated in TgR versus TmR cells in response to chronic ER stress. Additionally, bioenergetic analyses in both resistant cell lines showed a shift toward aerobic glycolysis ('Warburg effect') and a defective complex I of the oxidative phosphorylation (OXPHOS) machinery. Furthermore, ER stress-resistant cells differentially activated the unfolded protein response (UPR) comprising IRE1α and ATF6 pathways. These findings display the wide portfolio of adaptive responses of neuronal cells to chronic ER stress. ER stress-resistant neuronal cells could be the basis to uncover molecular modulators of adaptation, resistance, and neuroprotection as potential pharmacological targets for preventing neurodegeneration.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:67 |
---|---|
Enthalten in: |
Redox biology - 67(2023) vom: 01. Nov., Seite 102943 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Pham, Thu Nguyen Minh [VerfasserIn] |
---|
Links: |
---|
Anmerkungen: |
Date Completed 30.10.2023 Date Revised 03.11.2023 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1016/j.redox.2023.102943 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM363759360 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM363759360 | ||
003 | DE-627 | ||
005 | 20231226094029.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/j.redox.2023.102943 |2 doi | |
028 | 5 | 2 | |a pubmed24n1212.xml |
035 | |a (DE-627)NLM363759360 | ||
035 | |a (NLM)37883843 | ||
035 | |a (PII)S2213-2317(23)00344-0 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Pham, Thu Nguyen Minh |e verfasserin |4 aut | |
245 | 1 | 0 | |a Adaptive responses of neuronal cells to chronic endoplasmic reticulum (ER) stress |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 30.10.2023 | ||
500 | |a Date Revised 03.11.2023 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved. | ||
520 | |a Accumulation of misfolded proteins or perturbation of calcium homeostasis leads to endoplasmic reticulum (ER) stress and is linked to the pathogenesis of neurodegenerative diseases. Hence, understanding the ability of neuronal cells to cope with chronic ER stress is of fundamental interest. Interestingly, several brain areas uphold functions that enable them to resist challenges associated with neurodegeneration. Here, we established novel clonal mouse hippocampal (HT22) cell lines that are resistant to prolonged (chronic) ER stress induced by thapsigargin (TgR) or tunicamycin (TmR) as in vitro models to study the adaption to ER stress. Morphologically, we observed a significant increase in vesicular und autophagosomal structures in both resistant lines and 'giant lysosomes', especially striking in TgR cells. While autophagic activity increased under ER stress, lysosomal function appeared slightly impaired; in both cell lines, we observed enhanced ER-phagy. However, proteomic analyses revealed that various protein clusters and signaling pathways were differentially regulated in TgR versus TmR cells in response to chronic ER stress. Additionally, bioenergetic analyses in both resistant cell lines showed a shift toward aerobic glycolysis ('Warburg effect') and a defective complex I of the oxidative phosphorylation (OXPHOS) machinery. Furthermore, ER stress-resistant cells differentially activated the unfolded protein response (UPR) comprising IRE1α and ATF6 pathways. These findings display the wide portfolio of adaptive responses of neuronal cells to chronic ER stress. ER stress-resistant neuronal cells could be the basis to uncover molecular modulators of adaptation, resistance, and neuroprotection as potential pharmacological targets for preventing neurodegeneration | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a Aerobic glycolysis | |
650 | 4 | |a ER stress resistance | |
650 | 4 | |a ER-Phagy | |
650 | 4 | |a Giant lysosomes | |
650 | 4 | |a Neuroprotection | |
650 | 4 | |a Warburg effect | |
650 | 7 | |a Protein Serine-Threonine Kinases |2 NLM | |
650 | 7 | |a EC 2.7.11.1 |2 NLM | |
650 | 7 | |a Endoribonucleases |2 NLM | |
650 | 7 | |a EC 3.1.- |2 NLM | |
700 | 1 | |a Perumal, Natarajan |e verfasserin |4 aut | |
700 | 1 | |a Manicam, Caroline |e verfasserin |4 aut | |
700 | 1 | |a Basoglu, Marion |e verfasserin |4 aut | |
700 | 1 | |a Eimer, Stefan |e verfasserin |4 aut | |
700 | 1 | |a Fuhrmann, Dominik C |e verfasserin |4 aut | |
700 | 1 | |a Pietrzik, Claus U |e verfasserin |4 aut | |
700 | 1 | |a Clement, Albrecht M |e verfasserin |4 aut | |
700 | 1 | |a Körschgen, Hagen |e verfasserin |4 aut | |
700 | 1 | |a Schepers, Jana |e verfasserin |4 aut | |
700 | 1 | |a Behl, Christian |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Redox biology |d 2013 |g 67(2023) vom: 01. Nov., Seite 102943 |w (DE-627)NLM22743725X |x 2213-2317 |7 nnns |
773 | 1 | 8 | |g volume:67 |g year:2023 |g day:01 |g month:11 |g pages:102943 |
856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.redox.2023.102943 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 67 |j 2023 |b 01 |c 11 |h 102943 |