Cigarette smoke toxin hydroquinone and misfolding pancreatic lipase variant cooperatively promote endoplasmic reticulum stress and cell death.
Mutation-induced protein misfolding of pancreatic secretory enzymes and consequent endoplasmic reticulum stress can cause chronic pancreatitis. A recent study revealed that cigarette smoke also increases the risk of the disease through endoplasmic reticulum stress. Here, we investigated the cumulati...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0269936 |
| _version_ | 1818048547702964224 |
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| author | Norbert Kassay Vanda Toldi József Tőzsér András Szabó |
| author_facet | Norbert Kassay Vanda Toldi József Tőzsér András Szabó |
| author_sort | Norbert Kassay |
| collection | DOAJ |
| description | Mutation-induced protein misfolding of pancreatic secretory enzymes and consequent endoplasmic reticulum stress can cause chronic pancreatitis. A recent study revealed that cigarette smoke also increases the risk of the disease through endoplasmic reticulum stress. Here, we investigated the cumulative cellular effect of the G233E misfolding human pancreatic lipase variant and hydroquinone; a main toxic constituent of cigarette smoke, using mammalian cell lines. We found that hydroquinone reduces cell viability on a dose-dependent manner through programmed cell death, and diminishes lipase secretion without affecting its expression. Interestingly, hydroquinone decreased the viability more markedly in cells expressing the G233E lipase variant, than in cells producing wild-type lipase. The more substantial viability loss was due to increased endoplasmic reticulum stress, as demonstrated by elevated levels of X-box binding protein 1 mRNA splicing and immunoglobulin binding protein, NAD(P)H:quinone oxidoreductase 1 and C/EBP homologous protein expression. Unresolved endoplasmic reticulum stress, and especially up-regulation of the pro-apoptotic transcription factor C/EBP homologous protein were likely responsible for the increased cell death. Our observations demonstrated that the combination of hydroquinone and misfolding pancreatic lipase variant promote increased levels of endoplasmic reticulum stress and cell death, which may predispose to chronic pancreatitis. |
| first_indexed | 2024-12-10T10:23:25Z |
| format | Article |
| id | doaj.art-452a68a039bc4bee856b8e96690d7c76 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T10:23:25Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-452a68a039bc4bee856b8e96690d7c762022-12-22T01:52:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01176e026993610.1371/journal.pone.0269936Cigarette smoke toxin hydroquinone and misfolding pancreatic lipase variant cooperatively promote endoplasmic reticulum stress and cell death.Norbert KassayVanda ToldiJózsef TőzsérAndrás SzabóMutation-induced protein misfolding of pancreatic secretory enzymes and consequent endoplasmic reticulum stress can cause chronic pancreatitis. A recent study revealed that cigarette smoke also increases the risk of the disease through endoplasmic reticulum stress. Here, we investigated the cumulative cellular effect of the G233E misfolding human pancreatic lipase variant and hydroquinone; a main toxic constituent of cigarette smoke, using mammalian cell lines. We found that hydroquinone reduces cell viability on a dose-dependent manner through programmed cell death, and diminishes lipase secretion without affecting its expression. Interestingly, hydroquinone decreased the viability more markedly in cells expressing the G233E lipase variant, than in cells producing wild-type lipase. The more substantial viability loss was due to increased endoplasmic reticulum stress, as demonstrated by elevated levels of X-box binding protein 1 mRNA splicing and immunoglobulin binding protein, NAD(P)H:quinone oxidoreductase 1 and C/EBP homologous protein expression. Unresolved endoplasmic reticulum stress, and especially up-regulation of the pro-apoptotic transcription factor C/EBP homologous protein were likely responsible for the increased cell death. Our observations demonstrated that the combination of hydroquinone and misfolding pancreatic lipase variant promote increased levels of endoplasmic reticulum stress and cell death, which may predispose to chronic pancreatitis.https://doi.org/10.1371/journal.pone.0269936 |
| spellingShingle | Norbert Kassay Vanda Toldi József Tőzsér András Szabó Cigarette smoke toxin hydroquinone and misfolding pancreatic lipase variant cooperatively promote endoplasmic reticulum stress and cell death. PLoS ONE |
| title | Cigarette smoke toxin hydroquinone and misfolding pancreatic lipase variant cooperatively promote endoplasmic reticulum stress and cell death. |
| title_full | Cigarette smoke toxin hydroquinone and misfolding pancreatic lipase variant cooperatively promote endoplasmic reticulum stress and cell death. |
| title_fullStr | Cigarette smoke toxin hydroquinone and misfolding pancreatic lipase variant cooperatively promote endoplasmic reticulum stress and cell death. |
| title_full_unstemmed | Cigarette smoke toxin hydroquinone and misfolding pancreatic lipase variant cooperatively promote endoplasmic reticulum stress and cell death. |
| title_short | Cigarette smoke toxin hydroquinone and misfolding pancreatic lipase variant cooperatively promote endoplasmic reticulum stress and cell death. |
| title_sort | cigarette smoke toxin hydroquinone and misfolding pancreatic lipase variant cooperatively promote endoplasmic reticulum stress and cell death |
| url | https://doi.org/10.1371/journal.pone.0269936 |
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