title: Phenyl acyl acids attenuate the unfolded protein response in tunicamycin-treated neuroblastoma cells.
abstract: Understanding how neural cells handle proteostasis stress in the endoplasmic reticulum (ER) is important to decipher the mechanisms that underlie the cell death associated with neurodegenerative diseases and to design appropriate therapeutic tools. Here we have compared the sensitivity of a human neuroblastoma cell line (SH-SY5H) to the ER stress caused by an inhibitor of protein glycosylation with that observed in human embryonic kidney (HEK-293T) cells. In response to stress, SH-SY5H cells increase the expression of mRNA encoding downstream effectors of ER stress sensors and transcription factors related to the unfolded protein response (the spliced X-box binding protein 1, CCAAT-enhancer-binding protein homologous protein, endoplasmic reticulum-localized DnaJ homologue 4 and asparagine synthetase). Tunicamycin-induced death of SH-SY5H cells was prevented by terminal aromatic substituted butyric or valeric acids, in association with a decrease in the mRNA expression of stress-related factors, and in the accumulation of the ATF4 protein. Interestingly, this decrease in ATF4 protein occurs without modifying the phosphorylation of the translation initiation factor eIF2α. Together, these results show that when short chain phenyl acyl acids alleviate ER stress in SH-SY5H cells their survival is enhanced.
authors: Cell and Molecular Neuropharmacology Laboratory, Neurosciences Division, Center for Applied Medical Research - CIMA, University of Navarra, Pamplona, Spain.
authors: Marta
authors: M
authors: Zamarbide
authors: Eva
authors: E
authors: Martinez-Pinilla
authors: Ana
authors: A
authors: Ricobaraza
authors: Tomás
authors: T
authors: Aragón
authors: Rafael
authors: R
authors: Franco
authors: Alberto
authors: A
authors: Pérez-Mediavilla
mesh_terms: D051701:Activating Transcription Factor 4 / Q000235:genetics / Q000378:metabolism; D001217:Aspartate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006031:Glycosylation; D057809:HEK293 Cells; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010421:Pentanoic Acids / Q000494:pharmacology*; D010654:Phenylbutyrates / Q000494:pharmacology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014415:Tunicamycin / Q000494:pharmacology*; D056811:Unfolded Protein Response / Q000187:drug effects* / Q000235:genetics
chemical_list: C497109:ATF4 protein, human; D022762:CCAAT-Enhancer-Binding Proteins; C494646:DNAJA4 protein, human; D015852:Eukaryotic Initiation Factor-2; D050956:HSP40 Heat-Shock Proteins; C492666:NFX1 protein, human; D010421:Pentanoic Acids; D010654:Phenylbutyrates; D012097:Repressor Proteins; D014415:Tunicamycin; D051701:Activating Transcription Factor 4; D001217:Aspartate-Ammonia Ligase; C400347:5-phenylvaleric acid
references: J Cell Physiol. 1987 Dec;133(3):553-9
references: 3693412
references: Neurobiol Aging. 2012 Sep;33(9):2200-9
references: 21803450
references: Neurology. 2006 Jan 24;66(2 Suppl 1):S74-8
references: 16432151
references: Semin Pediatr Neurol. 2006 Jun;13(2):121-31
references: 17027862
references: J Alzheimers Dis. 2011;26(1):187-97
references: 21593570
references: Biochemistry (Mosc). 2013 Jan;78(1):102-10
references: 23379566
references: Invest New Drugs. 2007 Apr;25(2):131-8
references: 17053987
references: Biochem J. 2009 Feb 1;417(3):695-703
references: 18840095
references: Cancer Res. 1978 Nov;38(11 Pt 1):3751-7
references: 29704
references: PLoS One. 2010 Feb 09;5(2):e9135
references: 20161760
references: Hippocampus. 2012 May;22(5):1040-50
references: 21069780
references: Science. 2006 Aug 25;313(5790):1137-40
references: 16931765
references: Science. 2007 Nov 9;318(5852):944-9
references: 17991856
references: Mol Cell. 2000 Dec;6(6):1355-64
references: 11163209
references: Curr Med Chem. 2011;18(36):5545-53
references: 22172064
references: Mol Cell. 2000 Nov;6(5):1099-108
references: 11106749
references: Biochem J. 2002 Sep 1;366(Pt 2):585-94
references: 12014989
references: Neuroscience. 2009 Sep 29;163(1):1-8
references: 19531374
references: Neuropsychopharmacology. 2009 Jun;34(7):1721-32
references: 19145227
references: Mol Ther. 2002 Jul;6(1):119-26
references: 12095312
references: Blood. 1994 Jul 1;84(1):339-43
references: 7517215
references: Science. 2010 May 7;328(5979):753-6
references: 20448184
references: J Biol Chem. 2011 Apr 29;286(17):14941-51
references: 21372141
references: Proc R Soc Lond B Biol Sci. 1972 Jul 25;182(1066):25-35
references: 4403084
references: Nature. 2009 Feb 5;457(7230):736-40
references: 19079237
references: Biol Pharm Bull. 2012;35(1):84-90
references: 22223342
references: J Gen Virol. 1977 Jul;36(1):59-74
references: 886304
references: Neuropsychopharmacology. 2010 Mar;35(4):870-80
references: 20010553
references: Mol Cell Neurosci. 2008 Oct;39(2):193-201
references: 18638560
references: Blood. 1995 Jan 1;85(1):43-9
references: 7528572
references: J Alzheimers Dis. 2009;18(1):131-9
references: 19625751
references: J Biol Chem. 2005 Jan 7;280(1):556-63
references: 15494404
references: Gene Expr. 2010;15(1):13-25
references: 21061914
references: Pediatr Res. 1991 Feb;29(2):147-50
references: 2014149
references: Amyotroph Lateral Scler. 2009 Apr;10(2):99-106
references: 18688762
references: Rev Neurosci. 2009;20(1):23-37
references: 19526732
references: Anal Biochem. 1987 Apr;162(1):156-9
references: 2440339