Docosahexaenoic acid protection against palmitic acid-induced lipotoxicity in NGF-differentiated PC12 cells involves enhancement of autophagy and inhibition of apoptosis and necroptosis.
Journal
Journal of neurochemistry
ISSN: 1471-4159
Titre abrégé: J Neurochem
Pays: England
ID NLM: 2985190R
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
11
09
2019
revised:
20
04
2020
accepted:
30
04
2020
pubmed:
8
5
2020
medline:
3
3
2021
entrez:
8
5
2020
Statut:
ppublish
Résumé
Lipotoxicity (LTx) leads to cellular dysfunction and cell death and has been proposed to be an underlying process during traumatic and hypoxic injuries and neurodegenerative conditions in the nervous system. This study examines cellular mechanisms responsible for docosahexaenoic acid (DHA 22:6 n-3) protection in nerve growth factor-differentiated pheochromocytoma (NGFDPC12) cells from palmitic acid (PAM)-mediated lipotoxicity (PAM-LTx). NGFDPC12 cells exposed to PAM show a significant lipotoxicity demonstrated by a robust loss of cell viability, apoptosis, and increased HIF-1α and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 gene expression. Treatment of NGFDPC12 cells undergoing PAM-LTx with the pan-caspase inhibitor ZVAD did not protect, but shifted the process from apoptosis to necroptosis. This shift in cell death mechanism was evident by the appearance of the signature necroptotic Topo I protein cleavage fragments, phosphorylation of mixed lineage kinase domain-like, and inhibition with necrostatin-1. Cultures exposed to PAM and co-treated with necrostatin-1 (necroptosis inhibitor) and rapamycin (autophagy promoter), showed a significant protection against PAM-LTx compared to necrostatin-1 alone. In addition, co-treatment with DHA, as well as 20:5 n-3, 20:4 n-6, and 22:5 n-3, in the presence of PAM protected NGFDPC12 cells against LTx. DHA-induced neuroprotection includes restoring normal levels of HIF-1α and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 transcripts and caspase 8 and caspase 3 activity, phosphorylation of beclin-1, de-phosphorylation of mixed lineage kinase domain-like, increase in LC3-II, and up-regulation of Atg7 and Atg12 genes, suggesting activation of autophagy and inhibition of necroptosis. Furthermore, DHA-induced protection was suppressed by the lysosomotropic agent chloroquine, an inhibitor of autophagy. We conclude that DHA elicits neuroprotection by regulating multiple cell death pathways including enhancement of autophagy and inhibiting apoptosis and necroptosis.
Identifiants
pubmed: 32379343
doi: 10.1111/jnc.15038
pmc: PMC7754135
doi:
Substances chimiques
Reactive Oxygen Species
0
Docosahexaenoic Acids
25167-62-8
Palmitic Acid
2V16EO95H1
Nerve Growth Factor
9061-61-4
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
559-576Subventions
Organisme : NIMHD NIH HHS
ID : P20 MD006988
Pays : United States
Organisme : NIGMS NIH HHS
ID : R25 GM060507
Pays : United States
Informations de copyright
© 2020 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.
Références
Basic Res Cardiol. 2012 Jul;107(4):270
pubmed: 22553001
FEBS Lett. 2010 Nov 19;584(22):4491-9
pubmed: 20974143
Cell Death Differ. 1998 Feb;5(2):183-90
pubmed: 10200463
Inflamm Res. 2015 Jan;64(1):21-9
pubmed: 25380745
Cell Res. 2012 Jan;22(1):43-61
pubmed: 21912435
PLoS One. 2017 May 2;12(5):e0176793
pubmed: 28463985
Toxicol Res. 2011 Jun;27(2):103-10
pubmed: 24278558
J Neurochem. 2000 Dec;75(6):2563-73
pubmed: 11080210
J Lipid Res. 1995 Feb;36(2):229-40
pubmed: 7751810
Drug Metab Pharmacokinet. 2009;24(4):300-7
pubmed: 19745557
Biochim Biophys Acta. 2013 Dec;1830(12):5427-34
pubmed: 23567799
Neuroscience. 2013;255:1-18
pubmed: 24042033
Autophagy. 2015;11(9):1636-51
pubmed: 26237736
Clin Transl Immunology. 2017 Jan 06;6(1):e124
pubmed: 28197335
Front Endocrinol (Lausanne). 2019 Mar 26;10:176
pubmed: 30972025
J Neurochem. 2008 Sep;106(5):2015-29
pubmed: 18513372
Biochemistry. 2004 Feb 3;43(4):1030-6
pubmed: 14744148
Reprod Sci. 2015 Feb;22(2):156-64
pubmed: 24872334
J Transplant. 2009;2009:701464
pubmed: 20130772
Reprod Biol Endocrinol. 2018 Oct 17;16(1):98
pubmed: 30333041
Exp Neurol. 1997 Jul;146(1):240-9
pubmed: 9225757
Brain Behav. 2018 Nov;8(11):e01123
pubmed: 30264903
J Neurotrauma. 2012 Feb 10;29(3):551-66
pubmed: 21970623
Cell Rep. 2014 Jan 16;6(1):70-80
pubmed: 24388754
Semin Cell Dev Biol. 2014 Nov;35:24-32
pubmed: 24582829
Neuroscience. 2014 Apr 25;266:91-101
pubmed: 24561219
Brain Res. 2010 Mar 8;1318:133-43
pubmed: 20043885
FEBS Lett. 2017 Sep;591(18):2730-2744
pubmed: 28833063
Br J Nutr. 2012 Jan;107(2):229-41
pubmed: 21733316
EMBO J. 2007 May 16;26(10):2527-39
pubmed: 17446862
Proc Natl Acad Sci U S A. 1989 Apr;86(8):2663-7
pubmed: 2704741
Trends Cardiovasc Med. 2002 Apr;12(3):134-8
pubmed: 12007739
J Am Chem Soc. 2003 May 28;125(21):6409-21
pubmed: 12785780
Cancer Cell. 2006 Jul;10(1):51-64
pubmed: 16843265
PLoS One. 2011 Jan 05;6(1):e15816
pubmed: 21246057
J Clin Invest. 1986 Mar;77(3):964-70
pubmed: 3949983
Oncotarget. 2017 Oct 1;8(58):98482-98494
pubmed: 29228704
J Exp Med. 1997 Apr 21;185(8):1481-6
pubmed: 9126928
Nutr Neurosci. 2020 Apr;23(4):321-334
pubmed: 30032721
Nat Rev Mol Cell Biol. 2014 Feb;15(2):81-94
pubmed: 24401948
Nature. 2006 Jun 15;441(7095):880-4
pubmed: 16625205
J Neurochem. 2003 Feb;84(4):655-68
pubmed: 12562510
Nat Immunol. 2000 Dec;1(6):489-95
pubmed: 11101870
J Lipid Res. 2006 Dec;47(12):2726-37
pubmed: 16960261
Biochim Biophys Acta. 2008 Nov-Dec;1781(11-12):685-93
pubmed: 18755291
Cell. 2009 Jun 12;137(6):1100-11
pubmed: 19524512
Cell Death Dis. 2011;2:e115
pubmed: 21359116
Brain Res. 2011 Jan 25;1370:64-79
pubmed: 21108938
Cell Death Differ. 2010 Feb;17(2):268-77
pubmed: 19713971
J Lipid Res. 1969 Jan;10(1):56-67
pubmed: 5773785
J Exp Med. 1996 Aug 1;184(2):765-70
pubmed: 8760832
J Lipid Res. 2016 Aug;57(8):1329-38
pubmed: 27146479
J Neurochem. 2020 Dec;155(5):559-576
pubmed: 32379343
Biochim Biophys Acta Biomembr. 2018 Oct;1860(10):1985-1993
pubmed: 29730243
Nature. 2006 Jun 15;441(7095):885-9
pubmed: 16625204
Biochimie. 2017 May;136:21-26
pubmed: 28013071
Arthritis Rheum. 2005 Jul;52(7):2133-45
pubmed: 15986368
Ann N Y Acad Sci. 2005 Aug;1053:137-47
pubmed: 16179516
Lipids. 2014 Aug;49(8):731-44
pubmed: 24972900
Diabetes. 2001 Aug;50(8):1771-7
pubmed: 11473037
Nutr Neurosci. 2018 Dec;21(10):695-714
pubmed: 28686542
Biochem Biophys Res Commun. 2013 Jun 28;436(2):212-6
pubmed: 23727581
Biochim Biophys Acta Biomembr. 2018 May;1860(5):1125-1134
pubmed: 29305832
Food Funct. 2019 Feb 20;10(2):1049-1061
pubmed: 30706921
Mol Cell. 2011 Aug 5;43(3):449-63
pubmed: 21737330
J Gastroenterol Hepatol. 2009 May;24(5):830-40
pubmed: 19207680
Autophagy. 2013 Sep;9(9):1321-33
pubmed: 23800795
Int J Mol Sci. 2014 Nov 13;15(11):20876-99
pubmed: 25402647
J Lipid Res. 1985 Sep;26(9):1015-35
pubmed: 3906008
Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15312-7
pubmed: 21876153
J Biol Chem. 2004 Mar 12;279(11):10822-8
pubmed: 14701813
Biochemistry. 2013 Oct 15;52(41):7254-61
pubmed: 24090054
Dev Cell. 2002 Mar;2(3):256-7
pubmed: 11879630
Neurobiol Aging. 2002 Sep-Oct;23(5):843-53
pubmed: 12392789
Cancer Res. 1997 May 15;57(10):1835-40
pubmed: 9157970
Cell. 2014 Mar 27;157(1):65-75
pubmed: 24679527
J Lipid Res. 2015 Mar;56(3):502-14
pubmed: 25605873
Lipids. 2017 Nov;52(11):885-900
pubmed: 28875399
Cell Death Differ. 2016 May;23(5):748-56
pubmed: 26915291
J Neurochem. 2015 Jan;132(1):85-98
pubmed: 25147052
J Biol Chem. 2012 Apr 27;287(18):14364-76
pubmed: 22408252
PLoS One. 2012;7(7):e41831
pubmed: 22848625
Acta Pharmacol Sin. 2014 Apr;35(4):504-12
pubmed: 24608675
Neurochem Res. 2004 Feb;29(2):469-79
pubmed: 15002746
Cardiovasc Drugs Ther. 2007 Aug;21(4):227-33
pubmed: 17665295
Front Mol Neurosci. 2018 Jan 23;11:10
pubmed: 29410613
Arthritis Rheum. 2001 Nov;44(11):2642-52
pubmed: 11710720
Brain Res. 2015 Nov 19;1627:80-9
pubmed: 26410780
Mol Med. 2012 May 09;18:577-86
pubmed: 22371307
Neurosci Lett. 2005 Aug 26;384(3):288-93
pubmed: 15939536
Cell Death Differ. 2010 Jun;17(6):922-30
pubmed: 20010783
Acta Neuropathol. 2015 Mar;129(3):337-62
pubmed: 25367385
J Biol Chem. 2004 Aug 6;279(32):33368-78
pubmed: 15145933
EMBO J. 2000 Apr 17;19(8):1784-93
pubmed: 10775263
J Neurochem. 1998 Jan;70(1):24-30
pubmed: 9422343
J Neurochem. 2002 Nov;83(3):515-24
pubmed: 12390513
J Neurotrauma. 2013 May 15;30(10):853-68
pubmed: 23294084
Oncotarget. 2016 Aug 30;7(35):57391-57413
pubmed: 27429198
J Neurosci Res. 2009 Apr;87(5):1207-18
pubmed: 18951473
Oncogene. 2010 Mar 25;29(12):1717-9
pubmed: 20101204
Chem Biol Interact. 2006 Nov 7;163(3):207-17
pubmed: 16982041
Semin Cell Dev Biol. 2014 Nov;35:14-23
pubmed: 25087983
Mol Nutr Food Res. 2018 Oct;62(20):e1800322
pubmed: 30102465
Oncogene. 2013 Jul 4;32(27):3263-73
pubmed: 22890322
Curr Opin Immunol. 2014 Feb;26:76-89
pubmed: 24556404
Cell Death Differ. 2011 Apr;18(4):656-65
pubmed: 21052097
Inflamm Res. 2014 Oct;63(10):859-71
pubmed: 25095742
Am J Physiol. 1998 Oct;275(4):G638-44
pubmed: 9756491
Cell. 1995 May 19;81(4):513-23
pubmed: 7538908
Science. 2014 Mar 21;343(6177):1357-60
pubmed: 24557836
Diabetes. 2005 Oct;54(10):2917-24
pubmed: 16186393
Oncogene. 2012 Dec 6;31(49):5045-60
pubmed: 22310284
J Immunol. 2008 Jul 1;181(1):197-207
pubmed: 18566385
Nat Chem Biol. 2008 May;4(5):313-21
pubmed: 18408713
J Biol Chem. 2004 Jun 4;279(23):23882-91
pubmed: 15051725
J Cereb Blood Flow Metab. 2011 Jan;31(1):178-89
pubmed: 20571523
Annu Rev Nutr. 2014;34:281-303
pubmed: 24850384
Eur J Pharmacol. 2016 Aug 15;785:44-49
pubmed: 26632493
Biochem Soc Trans. 2006 Dec;34(Pt 6):1341-6
pubmed: 17073815