title: α-Lipoic acid ameliorates mitochondrial impairment and reverses apoptosis in FABP3-overexpressing embryonic cancer cells.
abstract: Fatty acid-binding protein 3 (FABP3) is a low molecular weight protein with distinct tissue distribution, which may play an important role in fatty acid transport, cell growth, cellular signaling, and gene transcription. We have previously shown FABP3 was more highly expressed in myocardium with ventricular septal defects than in normal myocardium and furthermore, that overexpression of FABP3 causes mitochondrial dysfunction and induces apoptosis in the P19 mouse teratocarcinoma cell line (P19), which is a suitable model for the investigation of cardiac differentiation at the molecular and functional levels. α-Lipoic acid (α-LA), a natural dithiol compound with antioxidant properties, has been reported to protect mitochondrial function in cells. In this study, we established an FABP3-overexpressing P19 cell line for the investigation of the impact of α-LA on mitochondrial impairment and apoptosis in these cells. Mitochondrial morphology was evaluated by transmission electron microscopy, while the effects of α-LA on reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), intracellular ATP content and the amount of mitochondrial DNA were analyzed by flow cytometry, a commercially available assay and quantitative real-time PCR, respectively. The results revealed that α-LA ameliorated mitochondrial deformation and decreased intracellular ROS production. Furthermore, the MMP, intracellular ATP synthesis and the amount of mitochondrial DNA were also increased. Most significantly, α-LA was shown to reverse apoptosis. Collectively, our results indicate that abnormalities in FABP3 expression contribute to mitochondrial dysfunction and apoptosis, and that α-LA represents a suitable candidate for development as a treatment for apoptosis-related congenital cardiac malformations.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People's Republic of China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhou
authors.forename: Jin
authors.initials: J
authors.lastname: Jin
authors.forename: Guixian
authors.initials: G
authors.lastname: Song
authors.forename: Hailang
authors.initials: H
authors.lastname: Liu
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Chunmei
authors.initials: C
authors.lastname: Shi
authors.forename: Lingmei
authors.initials: L
authors.lastname: Qian
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054278:Embryonal Carcinoma Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D018243:Teratocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008063:Thioctic Acid / Q000494:pharmacology*; D014162:Transfection
chemical_list: C493408:FABP3 protein, human; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D008063:Thioctic Acid
references.citation: Biochem Biophys Res Commun. 2006 Mar 31;342(1):135-44
references.pmid: 16472770
references.citation: Circ Res. 1999 Feb 19;84(3):276-89
references.pmid: 10024301
references.citation: EMBO J. 2002 Apr 2;21(7):1695-703
references.pmid: 11927553
references.citation: Am J Physiol Regul Integr Comp Physiol. 2007 Feb;292(2):R920-6
references.pmid: 17008456
references.citation: Eur J Pharmacol. 2012 Mar 5;678(1-3):32-8
references.pmid: 22266491
references.citation: Biochem J. 1992 May 15;284 ( Pt 1):1-13
references.pmid: 1599389
references.citation: Cell Mol Life Sci. 2002 Jul;59(7):1096-116
references.pmid: 12222958
references.citation: Gen Pharmacol. 1997 Sep;29(3):315-31
references.pmid: 9378235
references.citation: J Am Coll Cardiol. 2002 Jun 19;39(12):1890-900
references.pmid: 12084585
references.citation: Mol Cell Biochem. 2009 Jan;320(1-2):141-8
references.pmid: 18839280
references.citation: Cardiovasc Res. 2003 May 1;58(2):410-22
references.pmid: 12757875
references.citation: Circ Res. 2004 Nov 12;95(10):957-70
references.pmid: 15539639
references.citation: Biochim Biophys Acta. 2006 May-Jun;1763(5-6):542-8
references.pmid: 16730811
references.citation: Science. 1998 Aug 28;281(5381):1309-12
references.pmid: 9721092
references.citation: Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):8271-6
references.pmid: 10393984
references.citation: J Biol Chem. 2011 Jan 7;286(1):380-90
references.pmid: 21044951
references.citation: Curr Opin Pharmacol. 2001 Apr;1(2):141-50
references.pmid: 11714088
references.citation: Cell Biochem Biophys. 2011 Jul;60(3):259-66
references.pmid: 21293949
references.citation: Int J Cardiol. 2004 Sep;96(3):409-17
references.pmid: 15301895
references.citation: Hypertension. 2012 Sep;60(3):659-68
references.pmid: 22753215
references.citation: Mol Cell Biochem. 2007 Feb;296(1-2):59-67
references.pmid: 16909303
references.citation: J Cell Biochem. 2012 Dec;113(12):3701-8
references.pmid: 22753283
references.citation: Arch Dis Child Fetal Neonatal Ed. 1999 Jul;81(1):F61-3
references.pmid: 10375365
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2653-8
references.pmid: 16477035
references.citation: Cell Mol Life Sci. 2006 May;63(10):1141-8
references.pmid: 16568242
references.citation: Biochim Biophys Acta. 2004 Mar 2;1688(2):95-101
references.pmid: 14990339
references.citation: Mol Aspects Med. 1999 Jun;20(3):139-84
references.pmid: 10626278
references.citation: Am J Physiol Heart Circ Physiol. 2012 Nov 15;303(10):H1237-44
references.pmid: 22961867