title: Glucose 6-phosphate dehydrogenase deficiency enhances germ cell apoptosis and causes defective embryogenesis in Caenorhabditis elegans.
abstract: Glucose 6-phosphate dehydrogenase (G6PD) deficiency, known as favism, is classically manifested by hemolytic anemia in human. More recently, it has been shown that mild G6PD deficiency moderately affects cardiac function, whereas severe G6PD deficiency leads to embryonic lethality in mice. How G6PD deficiency affects organisms has not been fully elucidated due to the lack of a suitable animal model. In this study, G6PD-deficient Caenorhabditis elegans was established by RNA interference (RNAi) knockdown to delineate the role of G6PD in animal physiology. Upon G6PD RNAi knockdown, G6PD activity was significantly hampered in C. elegans in parallel with increased oxidative stress and DNA oxidative damage. Phenotypically, G6PD-knockdown enhanced germ cell apoptosis (2-fold increase), reduced egg production (65% of mock), and hatching (10% of mock). To determine whether oxidative stress is associated with G6PD knockdown-induced reproduction defects, C. elegans was challenged with a short-term hydrogen peroxide (H2O2). The early phase egg production of both mock and G6PD-knockdown C. elegans were significantly affected by H2O2. However, H2O2-induced germ cell apoptosis was more dramatic in mock than that in G6PD-deficient C. elegans. To investigate the signaling pathways involved in defective oogenesis and embryogenesis caused by G6PD knockdown, mutants of p53 and mitogen-activated protein kinase (MAPK) pathways were examined. Despite the upregulation of CEP-1 (p53), cep-1 mutation did not affect egg production and hatching in G6PD-deficient C. elegans. Neither pmk-1 nor mek-1 mutation significantly affected egg production, whereas sek-1 mutation further decreased egg production in G6PD-deficient C. elegans. Intriguingly, loss of function of sek-1 or mek-1 dramatically rescued defective hatching (8.3- and 9.6-fold increase, respectively) induced by G6PD knockdown. Taken together, these findings show that G6PD knockdown reduces egg production and hatching in C. elegans, which are possibly associated with enhanced oxidative stress and altered MAPK pathways, respectively.
authors: Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors: H-C
authors: HC
authors: Yang
authors: T-L
authors: TL
authors: Chen
authors: Y-H
authors: YH
authors: Wu
authors: K-P
authors: KP
authors: Cheng
authors: Y-H
authors: YH
authors: Lin
authors: M-L
authors: ML
authors: Cheng
authors: H-Y
authors: HY
authors: Ho
authors: S J
authors: SJ
authors: Lo
authors: D T-Y
authors: DT
authors: Chiu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D047108:Embryonic Development; D005854:Germ Cells / Q000378:metabolism*; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D048369:MAP Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016415:Sequence Alignment; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D006861:Hydrogen Peroxide; D005954:Glucosephosphate Dehydrogenase; D020928:Mitogen-Activated Protein Kinases; C463460:Pmk-1 protein, C elegans; D048369:MAP Kinase Kinase 1; C516678:mek-1 protein, C elegans
references: J Cell Sci. 2009 Nov 15;122(Pt 22):4081-8
references: 19843583
references: Dev Biol. 2005 Dec 15;288(2):317-33
references: 16336958
references: Dev Biol. 2001 Oct 1;238(1):145-56
references: 11784000
references: Environ Toxicol Pharmacol. 2011 Sep;32(2):175-84
references: 21843797
references: Circ Heart Fail. 2013 Jan;6(1):118-26
references: 23170010
references: Biochem J. 2003 Mar 15;370(Pt 3):935-43
references: 12466018
references: Cancer Res. 2003 Sep 1;63(17):5636-45
references: 14500406
references: Crit Rev Food Sci Nutr. 2012;52(2):162-71
references: 22059961
references: EMBO J. 1991 Mar;10(3):547-53
references: 2001672
references: Free Radic Biol Med. 2012 Apr 15;52(8):1285-93
references: 22330067
references: Chang Gung Med J. 2005 Sep;28(9):606-12
references: 16323551
references: Semin Hematol. 1990 Jan;27(1):1-40
references: 2405494
references: Cell Death Differ. 2006 Dec;13(12):2129-39
references: 16729024
references: Traffic. 2012 Jun;13(6):790-9
references: 22348310
references: Microbes Infect. 2011 Feb;13(2):109-20
references: 20971207
references: Reproduction. 2005 Jul;130(1):41-51
references: 15985630
references: Toxicol Sci. 2008 Dec;106(2):384-91
references: 18723824
references: Methods Mol Biol. 2000;132:365-86
references: 10547847
references: Chem Biol Interact. 2009 Jul 15;180(2):151-7
references: 19497412
references: EMBO J. 2002 Aug 15;21(16):4229-39
references: 12169625
references: Redox Rep. 2007;12(3):109-18
references: 17623517
references: WormBook. 2008 Sep 04;:1-20
references: 18781708
references: EMBO J. 2000 Oct 2;19(19):5148-56
references: 11013217
references: Development. 2008 Feb;135(3):431-40
references: 18094022
references: Mech Ageing Dev. 2011 Oct;132(10):480-7
references: 21855561
references: Free Radic Biol Med. 2000 Jul 15;29(2):156-69
references: 10980404
references: Nature. 2003 Jan 16;421(6920):231-7
references: 12529635
references: Adv Hematol. 2011;2011:398945
references: 21977034
references: Free Radic Biol Med. 2004 Mar 1;36(5):580-91
references: 14980702
references: J Infect Dis. 2008 Mar 15;197(6):812-6
references: 18269318
references: Blood. 1994 Dec 1;84(11):3613-36
references: 7949118
references: Antioxid Redox Signal. 2011 Mar 15;14(6):1023-37
references: 20649472
references: Free Radic Biol Med. 2009 Sep 1;47(5):529-35
references: 19497363
references: FEBS Lett. 1998 Oct 9;436(3):411-4
references: 9801159
references: Nat Rev Genet. 2002 May;3(5):356-69
references: 11988761
references: Science. 1998 Dec 11;282(5396):2012-8
references: 9851916
references: Free Radic Biol Med. 2010 Aug 1;49(3):361-73
references: 20420899
references: J Gen Virol. 2008 Sep;89(Pt 9):2080-2089
references: 18753216
references: Cell. 1999 Jan 22;96(2):291-302
references: 9988222
references: Dev Cell. 2004 Dec;7(6):801-14
references: 15572124
references: PLoS One. 2011 Jan 05;6(1):e15847
references: 21246053
references: Genetics. 2009 Nov;183(3):965-77
references: 19720857
references: Ann Hematol. 2011 Jul;90(7):769-75
references: 21302115
references: Nat Rev Genet. 2001 Jun;2(6):474-9
references: 11389464
references: Blood Cells Mol Dis. 2012 Apr 15;48(4):203-8
references: 22364808
references: Cell. 2001 Jan 12;104(1):43-56
references: 11163239
references: Nat Rev Genet. 2007 Jul;8(7):518-32
references: 17549065
references: Annu Rev Nutr. 2001;21:121-40
references: 11375432