Chemical chaperone, TUDCA unlike PBA, mitigates protein aggregation efficiently and resists ER and non-ER stress induced HepG2 cell death

Abstract Stress induced BSA (bovine serum albumin) protein aggregation is effectively mitigated in vitro by TUDCA (tauroursodeoxycholic acid) than by PBA (4- phenylbutyric acid), chemical chaperones approved by FDA for the treatment of biliary cirrhosis and urea cycle disorders respectively. TUDCA,...

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Autores principales:	Jagadeesh Kumar Uppala, Amina R. Gani, Kolluru V. A. Ramaiah
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9874ed970ecb46d7ae42e573fb0257e6
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spelling	oai:doaj.org-article:9874ed970ecb46d7ae42e573fb0257e62021-12-02T11:52:41ZChemical chaperone, TUDCA unlike PBA, mitigates protein aggregation efficiently and resists ER and non-ER stress induced HepG2 cell death10.1038/s41598-017-03940-12045-2322https://doaj.org/article/9874ed970ecb46d7ae42e573fb0257e62017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03940-1https://doaj.org/toc/2045-2322Abstract Stress induced BSA (bovine serum albumin) protein aggregation is effectively mitigated in vitro by TUDCA (tauroursodeoxycholic acid) than by PBA (4- phenylbutyric acid), chemical chaperones approved by FDA for the treatment of biliary cirrhosis and urea cycle disorders respectively. TUDCA, unlike PBA, enhances trypsin mediated digestion of BSA. TUDCA activates PERK, an ER-resident kinase that phosphorylates the alpha-subunit of eukaryotic initiation factor2 (eIF2α) and promotes the expression of activated transcription factor 4 (ATF4) in HepG2 cells. In contrast, PBA induced eIF2α phosphorylation is not mediated by PERK activation and results in low ATF4 expression. Neither chaperones promote expression of BiP, an ER chaperone, and CHOP (C/EBP homologous protein), downstream target of eIF2α-ATF4 pathway. Both chaperones mitigate tunicamycin induced PERK-eIF2α-ATF4-CHOP arm of UPR and expression of BiP. TUDCA, unlike PBA does not decrease cell viability and it also mitigates tunicamycin, UV-irradiation and PBA induced PARP (poly ADP-ribose polymerase) cleavage and cell death. These findings therefore suggest that TUDCA’s antiapoptotic activity to protect HepG2 cells and PBA’s activity that limits tumor cell progression may be important while considering their therapeutic potential.Jagadeesh Kumar UppalaAmina R. GaniKolluru V. A. RamaiahNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jagadeesh Kumar Uppala Amina R. Gani Kolluru V. A. Ramaiah Chemical chaperone, TUDCA unlike PBA, mitigates protein aggregation efficiently and resists ER and non-ER stress induced HepG2 cell death
description	Abstract Stress induced BSA (bovine serum albumin) protein aggregation is effectively mitigated in vitro by TUDCA (tauroursodeoxycholic acid) than by PBA (4- phenylbutyric acid), chemical chaperones approved by FDA for the treatment of biliary cirrhosis and urea cycle disorders respectively. TUDCA, unlike PBA, enhances trypsin mediated digestion of BSA. TUDCA activates PERK, an ER-resident kinase that phosphorylates the alpha-subunit of eukaryotic initiation factor2 (eIF2α) and promotes the expression of activated transcription factor 4 (ATF4) in HepG2 cells. In contrast, PBA induced eIF2α phosphorylation is not mediated by PERK activation and results in low ATF4 expression. Neither chaperones promote expression of BiP, an ER chaperone, and CHOP (C/EBP homologous protein), downstream target of eIF2α-ATF4 pathway. Both chaperones mitigate tunicamycin induced PERK-eIF2α-ATF4-CHOP arm of UPR and expression of BiP. TUDCA, unlike PBA does not decrease cell viability and it also mitigates tunicamycin, UV-irradiation and PBA induced PARP (poly ADP-ribose polymerase) cleavage and cell death. These findings therefore suggest that TUDCA’s antiapoptotic activity to protect HepG2 cells and PBA’s activity that limits tumor cell progression may be important while considering their therapeutic potential.
format	article
author	Jagadeesh Kumar Uppala Amina R. Gani Kolluru V. A. Ramaiah
author_facet	Jagadeesh Kumar Uppala Amina R. Gani Kolluru V. A. Ramaiah
author_sort	Jagadeesh Kumar Uppala
title	Chemical chaperone, TUDCA unlike PBA, mitigates protein aggregation efficiently and resists ER and non-ER stress induced HepG2 cell death
title_short	Chemical chaperone, TUDCA unlike PBA, mitigates protein aggregation efficiently and resists ER and non-ER stress induced HepG2 cell death
title_full	Chemical chaperone, TUDCA unlike PBA, mitigates protein aggregation efficiently and resists ER and non-ER stress induced HepG2 cell death
title_fullStr	Chemical chaperone, TUDCA unlike PBA, mitigates protein aggregation efficiently and resists ER and non-ER stress induced HepG2 cell death
title_full_unstemmed	Chemical chaperone, TUDCA unlike PBA, mitigates protein aggregation efficiently and resists ER and non-ER stress induced HepG2 cell death
title_sort	chemical chaperone, tudca unlike pba, mitigates protein aggregation efficiently and resists er and non-er stress induced hepg2 cell death
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9874ed970ecb46d7ae42e573fb0257e6
work_keys_str_mv	AT jagadeeshkumaruppala chemicalchaperonetudcaunlikepbamitigatesproteinaggregationefficientlyandresistserandnonerstressinducedhepg2celldeath AT aminargani chemicalchaperonetudcaunlikepbamitigatesproteinaggregationefficientlyandresistserandnonerstressinducedhepg2celldeath AT kolluruvaramaiah chemicalchaperonetudcaunlikepbamitigatesproteinaggregationefficientlyandresistserandnonerstressinducedhepg2celldeath
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Chemical chaperone, TUDCA unlike PBA, mitigates protein aggregation efficiently and resists ER and non-ER stress induced HepG2 cell death

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