tert-Butyl Hydroperoxide (tBHP)-Induced Lipid Peroxidation and Embryonic Defects Resemble Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency in C. elegans

Abstract

G6PD is required for embryonic development in animals, as severe G6PD deficiency is lethal to mice, zebrafish and nematode. Lipid peroxidation is linked to membrane-associated embryonic defects in Caenorhabditis elegans (C. elegans). However, the direct link between lipid peroxidation and embryonic lethality has not been established. The aim of this study was to delineate the role of lipid peroxidation in gspd-1-knockdown (ortholog of g6pd) C. elegans during reproduction. tert-butyl hydroperoxide (tBHP) was used as an exogenous inducer. Short-term tBHP administration reduced brood size and enhanced germ cell death in C. elegans. The altered phenotypes caused by tBHP resembled GSPD-1 deficiency in C. elegans. Mechanistically, tBHP-induced malondialdehyde (MDA) production and stimulated calcium-independent phospholipase A2 (iPLA) activity, leading to disturbed oogenesis and embryogenesis. The current study provides strong evidence to support the notion that enhanced lipid peroxidation in G6PD deficiency promotes death of germ cells and impairs embryogenesis in C. elegans.

Impaired immune response and barrier function in GSPD-1-deficient C. elegans infected with Klebsiella pneumoniae

“…GSPD-1 is required during reproduction and embryonic development ( Yang et al., 2020 ; Yang et al., 2013 ). Although GSPD-1 deficiency does not affect growth during neither the larval stage nor the lifespan in adults, GSPD-1 knockdown at the larval stage results in enhanced germ cell apoptosis and embryonic pathologies.…”

“…RNAi knockdown was carried out by feeding dsRNA-expressed bacteria based on a recent report ( Yang et al., 2020 ). Briefly, gravid hermaphrodites fed on E. coli OP50 were treated with 1% hypochlorite bleach and a 0.5 M sodium hydroxide solution.…”

“…Insufficient G6PD due to mutations causes red cell-related clinical symptoms, including neonatal jaundice, favism, and drug or infection-induced hemolysis ( Luzzatto and Seneca, 2014 ). Severe G6PD deficiency disrupts lipid metabolism and the permeability barrier in nematode embryos leading to embryonic lethality ( Yang et al., 2020 ; Chen et al., 2017 ).…”

Glucose-6-Phosphate Dehydrogenase, Redox Homeostasis and Embryogenesis

“…Transient treatment of tert-butyl hydroperoxide (tBHP), an inducer of lipid peroxidation decreases brood size and increases germ cell apoptosis [48]. tBHP stimulates malondialdehyde (MDA) generation and up-regulates iPLA activity, thereby interfering with oogenesis and embryogenesis.…”

Contribution of quasi-fibrillar superstructures in peroxide quenching by collagen peptides derived from fish processing by-products and their application as natural food additives

“…Lipid-rich food products generate peroxyl ions upon being stored for a longer duration, even with necessary packaging precautions, consequently leading to various health problems upon consumption. The LPOI assay simulates the longer storage period by the addition of catalytic amounts of cumene hydroperoxide (hereafter referred to as cumene), a lipid radical generating compound that hastens the peroxyl formation process [52]. The resultant peroxide oxidizes Fe 2+…”