Conservation of an Ancient Oxidation Response That Controls Archaeal Epigenetic Traits Through Chromatin Protein Networks

AbstractEpigenetic variants of the archaeon Sulfolobus solfataricus called SARC have evolved heritable traits including extreme acid resistance, enhanced genome integrity and a conserved “SARC” transcriptome related to acid resistance. These traits appear to result from altered chromatin protein function related to the heritable hypomethylation of chromatin proteins Cren7 and Sso7D. To clarify how this might occur, ChIPseq and Affinity Purification Mass Spectrometry (AP-MS) were used to compare Cren7 and Sso7D genome binding sites and protein networks between lineages (wild type and SARC) and culture pH (pH 1 and 3). All SARC transcriptome loci were bound by these chromatin proteins but with invariant patterns indicating binding alone was insufficient to mediate the SARC traits. In contrast, chromosome association varied at other loci. Quantitative AP-MS was then used to identify protein interaction networks and these included transcription and DNA repair proteins implicated in the evolved heritable traits that varied in abundance between SARC and wild type strains. Protein networks included most of the S-adenosylmethionine (SAM) synthesis pathway including serine hydroxymethyltransferase (SHMT), whose abundance varied widely with culture pH. Because epigenetic marks are coupled to SAM pools and oxidative stress in eukaryotes, occurrence of a similar process was investigated here. Archaeal SAM pools were depleted by treatment with SAM pathway inhibitors, acid or oxidative stress and, like eukaryotes, levels were raised by vitamin B12 and methionine supplementation. We propose that in archaea, oxidation-induced SAM pool depletion acting through an SHMT sensor, drove chromatin protein hypomethylation and thereby protein network changes that established the evolved SARC epigenetic traits.Significance StatementArchaea and eukaryotes share many molecular processes, including chromatin-mediated epigenetic inheritance of traits. As with eukaryotes, archaeal protein complexes were formed between trait-related proteins and chromatin proteins, subject to chromatin protein methylation state. Oxidation-induced depletion of S-adenosylmethionine (SAM) pools likely resulted in chromatin protein hypomethylation. Subsequent chromatin enrichment of serine hydroxymethyltransferase as a response to oxidative stress could modulate methylation at specific genomic loci. The interplay between archaeal metabolism and chromatin appear consistent with patterns observed in eukaryotes and indicate the existence of an ancient oxidation signal transduction pathway controlling epigenetics.

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Role of ςB in Heat, Ethanol, Acid, and Oxidative Stress Resistance and during Carbon Starvation inListeria monocytogenes

Applied and Environmental Microbiology ◽

10.1128/aem.67.10.4454-4457.2001 ◽

2001 ◽

Vol 67 (10) ◽

pp. 4454-4457 ◽

Cited By ~ 170

Author(s):

Adriana Ferreira ◽

Conor P. O'Byrne ◽

Kathryn J. Boor

Keyword(s):

Oxidative Stress ◽

Stationary Phase ◽

Stress Resistance ◽

Parent Strain ◽

Acid Resistance ◽

Carbon Starvation ◽

Wild Type ◽

Oxidative Stress Resistance ◽

And Oxidative Stress ◽

Dependent Mechanism

ABSTRACT To determine the contribution of sigma B (ςB) to survival of stationary-phase Listeria monocytogenescells following exposure to environmental stresses, we compared the viability of strain 10403S with that of an isogenic nonpolarsigB null mutant strain after exposure to heat (50°C), ethanol (16.5%), or acid (pH 2.5). Strain viabilities were also determined under the same conditions in cultures that had been previously exposed to sublethal levels of the same stresses (45°C, 5% ethanol, or pH 4.5). The ΔsigB and wild-type strains had similar viabilities following exposure to ethanol and heat, but the ΔsigB strain was almost 10,000-fold more susceptible to lethal acid stress than its parent strain. However, a 1-h preexposure to pH 4.5 yielded a 1,000-fold improvement in viability for the ΔsigB strain. These results suggest the existence in L. monocytogenes of both a ςB-dependent mechanism and a pH-dependent mechanism for acid resistance in the stationary phase. ςB contributed to resistance to both oxidative stress and carbon starvation inL. monocytogenes. The ΔsigB strain was 100-fold more sensitive to 13.8 mM cumene hydroperoxide than the wild-type strain. Following glucose depletion, the ΔsigB strain lost viability more rapidly than the parent strain. ςB contributions to viability during carbon starvation and to acid resistance and oxidative stress resistance support the hypothesis that ςB plays a role in protecting L. monocytogenes against environmental adversities.

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Nonmutational mechanism of inheritance in the Archaeon Sulfolobus solfataricus

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1808221115 ◽

2018 ◽

Vol 115 (48) ◽

pp. 12271-12276 ◽

Cited By ~ 5

Author(s):

Sophie Payne ◽

Samuel McCarthy ◽

Tyler Johnson ◽

Erica North ◽

Paul Blum

Keyword(s):

Gene Expression ◽

Chromatin Remodeling ◽

Chromatin Structure ◽

Genome Stability ◽

Sulfolobus Solfataricus ◽

Acid Resistance ◽

Wild Type ◽

Control Locus ◽

Super Acid ◽

Chromatin Proteins

Epigenetic phenomena have not yet been reported in archaea, which are presumed to use a classical genetic process of heritability. Here, analysis of independent lineages of Sulfolobus solfataricus evolved for enhanced fitness implicated a non-Mendelian basis for trait inheritance. The evolved strains, called super acid-resistant Crenarchaeota (SARC), acquired traits of extreme acid resistance and genome stability relative to their wild-type parental lines. Acid resistance was heritable because it was retained regardless of extensive passage without selection. Despite the hereditary pattern, in one strain, it was impossible for these SARC traits to result from mutation because its resequenced genome had no mutation. All strains also had conserved, heritable transcriptomes implicated in acid resistance. In addition, they had improved genome stability with absent or greatly decreased mutation and transposition relative to a passaged control. A mechanism that would confer these traits without DNA sequence alteration could involve posttranslationally modified archaeal chromatin proteins. To test this idea, homologous recombination with isogenic DNA was used to perturb native chromatin structure. Recombination at up-regulated loci from the heritable SARC transcriptome reduced acid resistance and gene expression in the majority of recombinants. In contrast, recombination at a control locus that was not part of the heritable transcriptome changed neither acid resistance nor gene expression. Variation in the amount of phenotypic and expression changes across individuals was consistent with Rad54-dependent chromatin remodeling that dictated crossover location and branch migration. These data support an epigenetic model implicating chromatin structure as a contributor to heritable traits.

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Lif Deficiency Leads to Iron Transportation Dysfunction in Ameloblasts

Journal of Dental Research ◽

10.1177/00220345211011986 ◽

2021 ◽

pp. 002203452110119

Author(s):

L. Fan ◽

Y.J. Ou ◽

Y.X. Zhu ◽

Y.D. Liang ◽

Y. Zhou ◽

...

Keyword(s):

Tooth Development ◽

Iron Status ◽

Acid Resistance ◽

Blue Staining ◽

Maturation Stage ◽

Wild Type ◽

Stat3 Signaling ◽

Stat3 Signaling Pathway ◽

Stem Cell Pluripotency ◽

Underlying Mechanisms

Leukemia inhibitory factor (LIF), a member of the interleukin 6 family of cytokines, is involved in skeletal metabolism, blastocyst implantation, and stem cell pluripotency maintenance. However, the role of LIF in tooth development needs to be elucidated. The aim of the present study was to investigate the effect of Lif deficiency on tooth development and to elucidate the functions of Lif during tooth development and the underlying mechanisms. First, it was found that the incisors of Lif-knockout mice had a much whiter color than those of wild-type mice. Although there were no structural abnormalities or defective mineralization according to scanning electronic microscopy and computed tomography analysis, 3-dimensional images showed that the length of incisors was shorter in Lif−/− mice. Microhardness and acid resistance assays showed that the hardness and acid resistance of the enamel surface of Lif−/− mice were decreased compared to those of wild-type mice. In Lif−/− mice, whose general iron status was comparable to that of the control mice, the iron content of the incisors was significantly reduced, as confirmed by energy-dispersive X-ray spectroscopy (EDS) and Prussian blue staining. Histological staining showed that the cell length of maturation-stage ameloblasts was shorter in Lif−/− mice. Likewise, decreased expression of Tfrc and Slc40a1, both of which are crucial proteins for iron transportation, was observed in Lif−/− mice and Lif-knockdown ameloblast lineage cell lines, according to quantitative reverse transcription polymerase chain reaction, immunohistochemistry, and Western blot. Moreover, the upregulation of Tfrc and Slc40a1 induced by Lif stimulation was blocked by Stattic, a signal transducer and activator of transcription 3 (Stat3) signaling inhibitor. These results suggest that Lif deficiency inhibits iron transportation in the maturation-stage ameloblasts, and Lif modulates expression of Tfrc and Slc40a1 through the Stat3 signaling pathway during enamel development.

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Streblus asper Lour. exerts MAPK and SKN-1 mediated anti-aging, anti-photoaging activities and imparts neuroprotection by ameliorating Aβ in Caenorhabditis elegans

Nutrition and Healthy Aging ◽

10.3233/nha-210121 ◽

2021 ◽

pp. 1-17

Author(s):

Mani Iyer Prasanth ◽

James Michael Brimson ◽

Dicson Sheeja Malar ◽

Anchalee Prasansuklab ◽

Tewin Tencomnao

Keyword(s):

Oxidative Stress ◽

Caenorhabditis Elegans ◽

Stress Resistance ◽

Vital Role ◽

Transgenic Strain ◽

Wild Type ◽

Neuroprotective Effects ◽

C Elegans ◽

Streblus Asper

BACKGROUND: Streblus asper Lour., has been reported to have anti-aging and neuroprotective efficacies in vitro. OBJECTIVE: To analyze the anti-aging, anti-photoaging and neuroprotective efficacies of S. asper in Caenorhabditis elegans. METHODS: C. elegans (wild type and gene specific mutants) were treated with S. asper extract and analyzed for lifespan and other health benefits through physiological assays, fluorescence microscopy, qPCR and Western blot. RESULTS: The plant extract was found to increase the lifespan, reduce the accumulation of lipofuscin and modulate the expression of candidate genes. It could extend the lifespan of both daf-16 and daf-2 mutants whereas the pmk-1 mutant showed no effect. The activation of skn-1 was observed in skn-1::GFP transgenic strain and in qPCR expression. Further, the extract can extend the lifespan of UV-A exposed nematodes along with reducing ROS levels. Additionally, the extract also extends lifespan and reduces paralysis in Aβ transgenic strain, apart from reducing Aβ expression. CONCLUSIONS: S. asper was able to extend the lifespan and healthspan of C. elegans which was independent of DAF-16 pathway but dependent on SKN-1 and MAPK which could play a vital role in eliciting the anti-aging, anti-photoaging and neuroprotective effects, as the extract could impart oxidative stress resistance and neuroprotection.

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Escherichia coli MutM Suppresses Illegitimate Recombination Induced by Oxidative Stress

Genetics ◽

10.1093/genetics/151.2.439 ◽

1999 ◽

Vol 151 (2) ◽

pp. 439-446 ◽

Cited By ~ 2

Author(s):

Masaaki Onda ◽

Katsuhiro Hanada ◽

Hirokazu Kawachi ◽

Hideo Ikeda

Keyword(s):

Oxidative Stress ◽

Escherichia Coli ◽

Hydrogen Peroxide ◽

Dna Damage ◽

Double Strand Breaks ◽

Illegitimate Recombination ◽

Recombination Analysis ◽

Wild Type ◽

Strand Breaks ◽

In The Wild

Abstract DNA damage by oxidative stress is one of the causes of mutagenesis. However, whether or not DNA damage induces illegitimate recombination has not been determined. To study the effect of oxidative stress on illegitimate recombination, we examined the frequency of λbio transducing phage in the presence of hydrogen peroxide and found that this reagent enhances illegitimate recombination. To clarify the types of illegitimate recombination, we examined the effect of mutations in mutM and related genes on the process. The frequency of λbio transducing phage was 5- to 12-fold higher in the mutM mutant than in the wild type, while the frequency in the mutY and mutT mutants was comparable to that of the wild type. Because 7,8-dihydro-8-oxoguanine (8-oxoG) and formamido pyrimidine (Fapy) lesions can be removed from DNA by MutM protein, these lesions are thought to induce illegitimate recombination. Analysis of recombination junctions showed that the recombination at Hotspot I accounts for 22 or 4% of total λbio transducing phages in the wild type or in the mutM mutant, respectively. The preferential increase of recombination at nonhotspot sites with hydrogen peroxide in the mutM mutant was discussed on the basis of a new model, in which 8-oxoG and/or Fapy residues may introduce double-strand breaks into DNA.

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Recent Progress in the Study of Peroxiredoxin in the Harmful Algal Bloom Species Chattonella marina

Antioxidants ◽

10.3390/antiox10020162 ◽

2021 ◽

Vol 10 (2) ◽

pp. 162

Author(s):

Yohei Shimasaki ◽

Koki Mukai ◽

Yuki Takai ◽

Xuchun Qiu ◽

Yuji Oshima

Keyword(s):

Oxidative Stress ◽

Growth Phase ◽

Critical Role ◽

High Irradiance ◽

Growth Potential ◽

Exponential Growth Phase ◽

Wild Type ◽

Chattonella Marina ◽

Strong Light ◽

Expression Strain

Peroxiredoxin (Prx) is a relatively recently discovered antioxidant enzyme family that scavenges peroxides and is known to be present in organisms from biological taxa ranging from bacteria to multicellular eukaryotes, including photosynthetic organisms. Although there have been many studies of the Prx family in higher plants, green algae, and cyanobacteria, few studies have concerned raphidophytes and dinoflagellates, which are among the eukaryotic algae that cause harmful algal blooms (HABs). In our proteomic study using 2-D electrophoresis, we found a highly expressed 2-Cys peroxiredoxin (2-CysPrx) in the raphidophyte Chattonella marina var. antiqua, a species that induces mass mortality of aquacultured fish. The abundance of the C. marina 2-CysPrx enzyme was highest in the exponential growth phase, during which photosynthetic activity was high, and it then decreased by about a factor of two during the late stationary growth phase. This pattern suggested that 2-CysPrx is a key enzyme involved in the maintenance of high photosynthesis activity. In addition, the fact that the depression of photosynthesis by excessively high irradiance was more severe in the 2-CysPrx low-expression strain (wild type) than in the normal-expression strain (wild type) of C. marina suggested that 2-CysPrx played a critical role in protecting the cell from oxidative stress caused by exposure to excessively high irradiance. In the field of HAB research, estimates of growth potential have been desired to predict the population dynamics of HABs for mitigating damage to fisheries. Therefore, omics approaches have recently begun to be applied to elucidate the physiology of the growth of HAB species. In this review, we describe the progress we have made using a molecular physiological approach to identify the roles of 2-CysPrx and other antioxidant enzymes in mitigating environmental stress associated with strong light and high temperatures and resultant oxidative stress. We also describe results of a survey of expressed Prx genes and their growth-phase-dependent behavior in C. marina using RNA-seq analysis. Finally, we speculate about the function of these genes and the ecological significance of 2-CysPrx, such as its involvement in circadian rhythms and the toxicity of C. marina to fish.

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Syntaxin-17-Dependent Mitochondrial Dynamics is Essential for Protection Against Oxidative-Stress-Induced Apoptosis

Antioxidants ◽

10.3390/antiox8110522 ◽

2019 ◽

Vol 8 (11) ◽

pp. 522 ◽

Cited By ~ 4

Author(s):

Wang ◽

Xiao ◽

Huang ◽

Liu

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dynamics ◽

Mitochondrial Fission ◽

Autophagic Flux ◽

Wild Type ◽

Dual Roles ◽

Defective Mutant ◽

U2os Cells ◽

Induced Apoptosis

In this study, cell death induced by the oxidant tert-butylhydroperoxide (tBH) was observed in U2OS cells; this phenotype was rescued by Syntaxin 17 (STX17) knockout (KO) but the mechanism is unknown. STX17 plays dual roles in autophagosome–lysosome fusion and mitochondrial fission. However, the contribution of the two functions of STX17 to apoptosis has not been extensively studied. Here, we sought to dissect the dual roles of STX17 in oxidative-stress-induced apoptosis by taking advantage of STX17 knockout cells and an autophagosome–lysosome fusion defective mutant of STX17. We generated STX17 knockout U2OS cells using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and the STX17 knockout cells were reconstituted with wild-type STX17 and its autophagosome–lysosome fusion defective mutant. Autophagy was assessed by autophagic flux assay, Monomer red fluorescent protein (mRFP)–GFP–LC3 assay and protease protection assay. Golgi, endoplasmic reticulum (ER)/ER–Golgi intermediate compartment (ERGIC) and mitochondrial dynamics were examined by staining the different indicator proteins. Apoptosis was evaluated by caspase cleavage assay. The general reactive oxygen species (ROS) were detected by flow cytometry. In STX17 complete knockout cells, sealed autophagosomes were efficiently formed but their fusion with lysosomes was less defective. The fusion defect was rescued by wild-type STX17 but not the autophagosome–lysosome fusion defective mutant. No obvious defects in Golgi, ERGIC or ER dynamics were observed. Mitochondria were significantly elongated, supporting a role of STX17 in mitochondria fission and the elongation caused by STX17 KO was reversed by the autophagosome–lysosome fusion defective mutant. The clearance of protein aggregation was compromised, correlating with the autophagy defect but not with mitochondrial dynamics. This study revealed a mixed role of STX17 in autophagy, mitochondrial dynamics and oxidative stress response. STX17 knockout cells were highly resistant to oxidative stress, largely due to the function of STX17 in mitochondrial fission rather than autophagy.

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Vasomotor responses in MnSOD-deficient mice

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01215.2003 ◽

2004 ◽

Vol 287 (3) ◽

pp. H1141-H1148 ◽

Cited By ~ 25

Author(s):

Jon J. Andresen ◽

Frank M. Faraci ◽

Donald D. Heistad

Keyword(s):

Oxidative Stress ◽

Acute Hypoxia ◽

Vasomotor Response ◽

Wild Type ◽

Similar Extent ◽

Sod Activity ◽

Vasomotor Function ◽

Mitochondrial Superoxide ◽

Prostaglandin F ◽

Deficient Mice

MnSOD is the only mammalian isoform of SOD that is necessary for life. MnSOD−/− mice die soon after birth, and MnSOD+/− mice are more susceptible to oxidative stress than wild-type (WT) mice. In this study, we examined vasomotor function responses in aortas of MnSOD+/− mice under normal conditions and during oxidative stress. Under normal conditions, contractions to serotonin (5-HT) and prostaglandin F2α (PGF2α), relaxation to ACh, and superoxide levels were similar in aortas of WT and MnSOD+/− mice. The mitochondrial inhibitor antimycin A reduced contraction to PGF2α and impaired relaxation to ACh to a similar extent in aortas of WT and MnSOD+/− mice. The Cu/ZnSOD and extracellular SOD inhibitor diethyldithiocarbamate (DDC) paradoxically enhanced contraction to 5-HT and superoxide more in aortas of WT mice than in MnSOD+/− mice. DDC impaired relaxation to ACh and reduced total SOD activity similarly in aortas of both genotypes. Tiron, a scavenger of superoxide, normalized contraction to 5-HT, relaxation to ACh, and superoxide levels in DDC-treated aortas of WT and MnSOD+/− mice. Hypoxia, which reportedly increases superoxide, reduced contractions to 5-HT and PGF2α similarly in aortas of WT and MnSOD+/− mice. The vasomotor response to acute hypoxia was similar in both genotypes. In summary, under normal conditions and during acute oxidative stress, vasomotor function is similar in WT and MnSOD+/− mice. We speculate that decreased mitochondrial superoxide production may preserve nitric oxide bioavailability during oxidative stress.

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RNA Interference-Mediated Inhibition of Wild-Type Torsin A Expression Increases Apoptosis Caused by Oxidative Stress in Cultured Cells

Neurochemical Research ◽

10.1007/s11064-010-0177-4 ◽

2010 ◽

Vol 35 (8) ◽

pp. 1214-1223 ◽

Cited By ~ 5

Author(s):

Xue-Ping Chen ◽

Xiao-Hui Hu ◽

Shu-Hui Wu ◽

Yang-Wei Zhang ◽

Bo Xiao ◽

...

Keyword(s):

Oxidative Stress ◽

Rna Interference ◽

Cultured Cells ◽

Wild Type

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CD40L controls obesity-associated vascular inflammation, oxidative stress, and endothelial dysfunction in high fat diet-treated and db/db mice

Cardiovascular Research ◽

10.1093/cvr/cvx197 ◽

2017 ◽

Vol 114 (2) ◽

pp. 312-323 ◽

Cited By ~ 11

Author(s):

Sebastian Steven ◽

Mobin Dib ◽

Michael Hausding ◽

Fatemeh Kashani ◽

Matthias Oelze ◽

...

Keyword(s):

Oxidative Stress ◽

Endothelial Dysfunction ◽

High Fat Diet ◽

Immune Cell ◽

Vascular Inflammation ◽

Human Study ◽

Isometric Tension ◽

Wild Type ◽

High Fat ◽

Aorta Ascendens

Abstract Aims CD40 ligand (CD40L) signaling controls vascular oxidative stress and related dysfunction in angiotensin-II-induced arterial hypertension by regulating vascular immune cell recruitment and platelet activation. Here we investigated the role of CD40L in experimental hyperlipidemia. Methods and results Male wild type and CD40L−/− mice (C57BL/6 background) were subjected to high fat diet for sixteen weeks. Weight, cholesterol, HDL, and LDL levels, endothelial function (isometric tension recording), oxidative stress (NADPH oxidase expression, dihydroethidium fluorescence) and inflammatory parameters (inducible nitric oxide synthase, interleukin-6 expression) were assessed. CD40L expression, weight, leptin and lipids were increased, and endothelial dysfunction, oxidative stress and inflammation were more pronounced in wild type mice on a high fat diet, all of which was almost normalized by CD40L deficiency. Similar results were obtained in diabetic db/db mice with CD40/TRAF6 inhibitor (6877002) therapy. In a small human study higher serum sCD40L levels and an inflammatory phenotype were detected in the blood and Aorta ascendens of obese patients (body mass index > 35) that underwent by-pass surgery. Conclusion CD40L controls obesity-associated vascular inflammation, oxidative stress and endothelial dysfunction in mice and potentially humans. Thus, CD40L represents a therapeutic target in lipid metabolic disorders which is a leading cause in cardiovascular disease.

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