Catalase T-Deficient Fission Yeast Meiocytes Show Resistance to Ionizing Radiation

Abstract

Environmental stress, reactive oxygen species (ROS), or ionizing radiation (IR) can induce adverse effects in organisms and their cells, including mutations and premature aging. DNA damage and its faulty repair can lead to cell death or promote cancer through the accumulation of mutations. Misrepair in germ cells is particularly dangerous as it may lead to alterations in developmental programs and genetic disease in the offspring. DNA damage pathways and radical defense mechanisms mediate resistance to genotoxic stresses. Here, we investigated, in the fission yeast Schizosaccharomyces pombe, the role of the H2O2-detoxifying enzyme cytosolic catalase T (Ctt1) and the Fe2+/Mn2+ symporter Pcl1 in protecting meiotic chromosome dynamics and gamete formation from radicals generated by ROS and IR. We found that wild-type and pcl1-deficient cells respond similarly to X ray doses of up to 300 Gy, while ctt1∆ meiocytes showed a moderate sensitivity to IR but a hypersensitivity to hydrogen peroxide with cells dying at >0.4 mM H2O2. Meiocytes deficient for pcl1, on the other hand, showed a resistance to hydrogen peroxide similar to that of the wild type, surviving doses >40 mM. In all, it appears that in the absence of the main H2O2-detoxifying pathway S. pombe meiocytes are able to survive significant doses of IR-induced radicals.

PFAS Environmental Pollution and Antioxidant Responses: An Overview of the Impact on Human Field

“…Increased ROS formation 1 , increased DNA damage 9 , antioxidant defense inhibition 10 [196] Homo sapiens PFOA, PFOS Estrogenicity and anti-estrogenicity 12 [202] Homo sapiens PFOA, PFOS, PFNA Estradiol production 13 , progesterone 13 production, testosterone production 13 [203] Homo sapiens PFOA, PFOS Thyroid diseases [213] Homo sapiens PFOA, PFOS Chronic kidney diseases [216] Homo sapiens PFHxS, PFOA, PFOS, PFNA Decreased eGFR 14 [217] Homo sapiens PFHxs, PFOA, PFOS Increased cholesterol outcomes 15 [218] Homo sapiens PFOA, PFOS, PFNA Hyperglycemia 16 , increased serum HDL cholesterol 16 , increased blood insulin 17 [219] Homo sapiens PFOA, PFOS Increased blood levels of glucocorticoid 17 , increased blood levels of androgenic hormones 18 [222]…”

“…Micropterus salmoides PFOS gpx up-regulation 8 , sod down-regulation 8 , cat up-regulation 8 , prdx down-regulation 8 [332] Mus musculus PFOA Lipid peroxidation 25 , amylase induction, lipase induction, sod1 up-regulation 5 , sod2 up-regulation5, gpx2 up-regulation 5 , nqo1 up-regulation 5 [204] Mus musculus PFOS Increased in peroxisomal fatty acid beta-oxidation 4 , increased peroxisomal catalase activity 4 [208] Mus musculus PFOA pparα up-regulation 5 , pparγ up-regulation 5 [209] Mus musculus PFOS Serum testosterone decrease 19 , epididymal sperm counts decrease, down-regulation of genes encoding testicular receptors for gonadotropin, growth hormone, insulin-like growth factor 1 and steroidogenic enzymes 5 [234] Mus musculus PFOA Damaged seminiferous tubules, reduced sperm quality, reduced serum testosterone and progesterone levels 13 , INSL3 enzyme decrease 23 , cytochrome P450 decrease 23 [235] Mus musculus PFOS Immune response induction 19 [269]…”

“…1 2 ,7 -dichlorofluorescein deacetate; 2 malondialdehyde; 3 4-chloro-1-methyl-7-trifluoromethylquinolinium methylsulfate; 4 enzymatic activity; 5 quantitative real-time PCR; 6 thiobarbituric acid reactive species; 7 MALDI-TOF-TOF mass spectrometry; 8 microarray; 9 comet assay; 10 total antioxidant capacity; 11 FACSort flow cytometry; 12 E-SCREEN bioassay; 13 Coat-a-count radioimmunoassay; 14 serum creatinine; 15 Ortho VITROS Clinical Analyzer; 16 enzymatic assay; 17 immunoenzymometric assay; 18 liquid chromatography-tandem mass spectrometry; 19 Enzyme Linked ImmunoSorbent Assay; 20 gas chromatography-mass spectrometry; 21 AutoDELFIA fully automated system; 22 isometric assay; 23 Wester blotting; 24 transactivation assay; 25 MitoSOX™ Red mitochondrial superoxide indicator; 26 ATP colorimetric assay; 27 10-N-nonyl-Acridine Orange; 28 mass spectrometry.…”

“…All living organisms respond to a high presence of ROS by increasing the expression of antioxidant enzymes and many other molecules that are elements of the defense and repair toward oxidative damage [10]. Enzymatic antioxidants include proteins such as superoxide dismutase (SOD) [11,12], catalase (CAT) [13], glutathione peroxidase (GPx) [14], peroxiredoxins (Prdx) [15,16], and methionine sulfoxide reductases (Msr) [17]. These enzymes represent a first line against ROS, but do not guarantee complete coverage from the risk of oxidative stress because some compounds, generated by their reactions, are still reactive and potentially cytotoxic, such as the hydrogen peroxide (H 2 O 2 ) produced by SOD.…”

Enzymatic and Non-Enzymatic Molecules with Antioxidant Function

“…Muhtadi et al investigated, in the yeast Schizosaccharomyces pombe , the role of CAT and the Fe 2+ /Mn 2+ symporter in protecting meiotic chromosome dynamic and gamete formation from radicals generated by ROS and ionizing radiation [ 19 ].…”