Phytopathogenic Cercosporoid Fungi—From Taxonomy to Modern Biochemistry and Molecular Biology

Phytopathogenic cercosporoid fungi have been investigated comprehensively due to their important role in causing plant diseases. A significant amount of research has been focused on the biology, morphology, systematics, and taxonomy of this group, with less of a focus on molecular or biochemical issues. Early and extensive research on these fungi focused on taxonomy and their classification based on in vivo features. Lately, investigations have mainly addressed a combination of characteristics such as morphological traits, host specificity, and molecular analyses initiated at the end of the 20th century. Some species that are important from an economic point of view have been more intensively investigated by means of genetic and biochemical methods to better understand the pathogenesis processes. Cercosporin, a photoactivated toxin playing an important role in Cercospora diseases, has been extensively studied. Understanding cercosporin toxicity in relation to reactive oxygen species (ROS) production facilitated the discovery and regulation of the cercosporin biosynthesis pathway, including the gene cluster encoding pathway enzymes. Furthermore, these fungi may be a source of other biotechnologically important compounds, e.g., industrially relevant enzymes. This paper reviews methods and important results of investigations of this group of fungi addressed at different levels over the years.

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A Three-Component-System Hypothesis of Psychosis

The British Journal of Psychiatry ◽

10.1192/s0007125000295962 ◽

1989 ◽

Vol 155 (S5) ◽

pp. 37-39 ◽

Cited By ~ 42

Author(s):

Hinderk M. Emrich

Keyword(s):

Human Brain ◽

Causative Factor ◽

Microscopic Level ◽

Point Of View ◽

Component System ◽

Pathogenetic Factor ◽

Pet Scans ◽

The Brain ◽

Different Levels

Hypotheses as to the pathogenesis of schizophrenia can be discussed at different levels of a possible manifestation of the causative factor: the macroscopic-morphological, the microscopic-morphological, and the molecular. Some abnormalities have been observed on all of them: e.g. increased ventricular-brain ratios in CT, hypofrontality in SPECT and in glucographic PET-scans, and other macromorphological abnormalities (for reviews cf. Bogerts 1984; Mundt, 1986; Bogerts et al, 1987), gliosis on a microscopic level (Stevens, 1982), and an increased dopamine-binding in in vivo receptor studies (PET as well as in post-mortem studies; Cazzullo, 1988). However, the diversity and variability of these findings point to the view that rather than there being a single distinct pathogenetic factor responsible for the pathogenesis of schizophrenic psychoses, a constitutional disposition exists, which can be described as a functional dysequilibrium within the human brain. From this point of view, schizophrenia would not appear as an inherited disorder of metabolism, but as a weakness of a neurobiological ‘system’, i.e. as an interactional disorder of a complex of networks, in which the interaction between different substructures is labile in such a way that under special conditions (e.g. ‘stress’), a decompensation (functional breakdown) results. In this sense, ‘vulnerability’ to schizophrenia may be interpreted as a consequence of a constitutional deficiency of the brain which results in an inability to stabilise, under specially challenging conditions, the interaction between different substructures of the human brain. Before this ‘functional dysequilibrium-hypothesis’ (which is a special form of a constitutional structural deficiency-hypothesis) is discussed, and before the question is raised as to which are the relevant dysequilibrated components, some indication will be given as to why such an hypothesis appears plausible.

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Loss of the SdhB, but Not the SdhA, Subunit of Complex II Triggers Reactive Oxygen Species-Dependent Hypoxia-Inducible Factor Activation and Tumorigenesis

Molecular and Cellular Biology ◽

10.1128/mcb.01338-07 ◽

2007 ◽

Vol 28 (2) ◽

pp. 718-731 ◽

Cited By ~ 262

Author(s):

Robert D. Guzy ◽

Bhumika Sharma ◽

Eric Bell ◽

Navdeep S. Chandel ◽

Paul T. Schumacker

Keyword(s):

Reactive Oxygen Species ◽

Rna Interference ◽

Growth Rates ◽

Hypoxia Inducible Factor ◽

Tumor Formation ◽

Ros Production ◽

Oxygen Species ◽

Complex Ii

ABSTRACT Mitochondrial complex II is a tumor suppressor comprised of four subunits (SdhA, SdhB, SdhC, and SdhD). Mutations in any of these should disrupt complex II enzymatic activity, yet defects in SdhA produce bioenergetic deficiency while defects in SdhB, SdhC, or SdhD induce tumor formation. The mechanisms underlying these differences are not known. We show that the inhibition of distal subunits of complex II, either pharmacologically or via RNA interference of SdhB, increases normoxic reactive oxygen species (ROS) production, increases hypoxia-inducible factor alpha (HIF-α) stabilization in an ROS-dependent manner, and increases growth rates in vitro and in vivo without affecting hypoxia-mediated activation of HIF-α. Proximal pharmacologic inhibition or RNA interference of complex II at SdhA, however, does not increase normoxic ROS production or HIF-α stabilization and results in decreased growth rates in vitro and in vivo. Furthermore, the enhanced growth rates resulting from SdhB suppression are inhibited by the suppression of HIF-1α and/or HIF-2α, indicating that the mechanism of SdhB-induced tumor formation relies upon ROS production and subsequent HIF-α activation. Therefore, differences in ROS production, HIF proliferation, and cell proliferation contribute to the differences in tumor phenotype in cells lacking SdhB as opposed to those lacking SdhA.

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Production, Signaling, and Scavenging Mechanisms of Reactive Oxygen Species in Fruit–Pathogen Interactions

International Journal of Molecular Sciences ◽

10.3390/ijms20122994 ◽

2019 ◽

Vol 20 (12) ◽

pp. 2994 ◽

Cited By ~ 17

Author(s):

Ying Wang ◽

Dongchao Ji ◽

Tong Chen ◽

Boqiang Li ◽

Zhanquan Zhang ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Pathogenic Fungi ◽

Ros Production ◽

Oxygen Species ◽

Ros Homeostasis ◽

Molecular Damage ◽

Different Levels ◽

In Cells

Reactive oxygen species (ROS) play a dual role in fruit–pathogen interaction, which largely depends on their different levels in cells. Fruit recognition of a pathogen immediately triggers an oxidative burst that is considered an integral part of the fruit defense response. ROS are also necessary for the virulence of pathogenic fungi. However, the accumulation of ROS in cells causes molecular damage and finally leads to cell death. In this review, on the basis of data regarding ROS production and the scavenging systems determining ROS homeostasis, we focus on the role of ROS in fruit defense reactions against pathogens and in fungi pathogenicity during fruit–pathogen interaction.

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Abstract 15983: Increased Mitochondrial Reactive Oxygen Species Lead to Deleterious JNK Signaling and Ischemia-Reperfusion Injury in AMPK-Inactivated Hearts

Circulation ◽

10.1161/circ.130.suppl_2.15983 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Vlad G Zaha ◽

Dake Qi ◽

Hui-Young Lee ◽

Xiaoyue Hu ◽

Xiaohong Wu ◽

...

Keyword(s):

Ischemia Reperfusion ◽

Reactive Oxygen ◽

Myocardial Necrosis ◽

Ros Production ◽

Oxygen Species ◽

Mitochondrial Reactive Oxygen Species ◽

Jnk Signaling ◽

Mitochondrial Ros

AMP-activated kinase (AMPK) is a key stress responsive kinase that regulates cellular adaptation to metabolic stress. Inactivation of AMPK in “kinase-dead” (KD) mice increases myocardial damage following ischemia-reperfusion (IR). We have also shown decreased mitochondrial respiration and increased mitochondrial reactive oxygen species (ROS) production and susceptibility to mitochondrial transition pore opening in KD hearts following IR. The aim of this study was to establish the importance of mitochondrial ROS production and downstream deleterious signaling to mediate tissue damage in absence of active AMPK in the heart. Detoxification of mitochondrial ROS requires conversion of hydrogen peroxide to water, therefore, we studied the effect of transgenic expression of mitochondrial catalase (MCAT) in wild type (WT) and KD mice. MCAT prevents mitochondrial hydrogen peroxide production independent of mitochondrial energy production. Myocardial necrosis was assessed in vitro after global ischemia-reperfusion and in vivo after LAD ligation and reperfusion. Mitogen activated protein kinase kinase 4 (MKK4) and downstream c-Jun terminal kinase (JNK) expression and phosphorylation was assessed in vivo. Increased necrosis in KD hearts following mild global ischemia (15 minutes) - reperfusion (10 minutes) in vitro, was prevented by expression of MCAT (WT vs. KD 17.8±4.1 vs. 50±4.1%, p<0.05 and MCAT-WT vs. MCAT-KD 16.9±4.8 vs. 29.3±4.4%, n.s., and factorial p<0.05). Total JNK protein was not increased in WT and KD hearts with or without expression of MCAT. After coronary occlusion in vivo, KD mice showed increased cardiac activation of MKK4/JNK pathway (p<0.05) as well as greater myocardial necrosis (p<0.05). MCAT expression prevented the excessive cardiac JNK activation observed during IR in KD mice in vivo. Inhibition of JNK with SP600125 (10μM) during in vivo IR also resulted in a significant decrease in necrosis in KD hearts (WT vs. KD 9.1±0.7 vs. 28.2±2.9%, p<0.05 and WT vs. KD with SP600125 8.5±0.5 vs. 10.2±1.1%, n.s. and factorial p<0.05, percentage of equivalent area at risk). Thus, AMPK activation during IR prevents excess mitochondrial reactive oxygen production and consequent JNK signaling, thus protecting against myocardial injury.

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C-junInhibits Mammary Apoptosis In Vivo

Molecular Biology of the Cell ◽

10.1091/mbc.e10-08-0705 ◽

2010 ◽

Vol 21 (23) ◽

pp. 4264-4274 ◽

Cited By ~ 14

Author(s):

Sanjay Katiyar ◽

Mathew C. Casimiro ◽

Luis Dettin ◽

Xiaoming Ju ◽

Erwin F. Wagner ◽

...

Keyword(s):

Germ Line ◽

Mammary Epithelial ◽

Conditional Knockout ◽

Ros Production ◽

Oxygen Species ◽

Mitochondrial Complex ◽

Cellular Apoptosis ◽

Laser Capture

c-jun, which is overexpressed in a number of human cancers encodes a critical component of the AP-1 complex. c-jun has been shown to either induce or inhibit cellular apoptosis. Germ line deletion of both c-jun alleles is embryonically lethal. To determine the role of the endogenous c-jun gene in apoptosis, we performed mammary epithelial cell–targeted somatic deletion using floxed c-jun (c-junf/f) conditional knockout mice. Laser capture microdissection demonstrated endogenous c-jun inhibits expression of apoptosis inducing genes and reactive oxygen species (ROS)-reducing genes (MnSOD, catalase). ROS have been implicated in apoptosis and undergo enzymatic elimination via MnSOD and CuZnSOD with further detoxification via catalase. c-jun–mediated survival was in part dependent on ROS production. c-jun–mediated repression of MnSOD and catalase occurred via mitochondrial complex I and NOX I. Collectively, these studies define a pivotal role of endogenous c-jun in promoting cell survival via maintaining mitochondrial integrity and expression of the key regulators of ROS production.

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LncRNA TUG1 mediates ischemic myocardial injury by targeting miR-132-3p/HDAC3 axis

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00444.2019 ◽

2020 ◽

Vol 318 (2) ◽

pp. H332-H344 ◽

Cited By ~ 8

Author(s):

Qiang Su ◽

Yang Liu ◽

Xiang-Wei Lv ◽

Ri-Xin Dai ◽

Xi-Heng Yang ◽

...

Keyword(s):

Myocardial Infarction ◽

Reactive Oxygen Species ◽

Noncoding Rna ◽

Ischemia Reperfusion ◽

Ros Production ◽

Oxygen Species ◽

Histone Deacetylase 3 ◽

Taurine Upregulated Gene 1

Increased production of reactive oxygen species (ROS) significantly contributed to the pathogenesis of acute myocardial infarction (AMI). Recent studies suggest that hypoxia upregulated the long noncoding RNA taurine upregulated gene 1 (TUG1). In this study, we explored the functional significance and molecular mechanisms of TUG1/miR-132-3p axis in ischemia-challenged cardiomyocytes. In primary cardiomyocytes challenged with H2O2, expressions of miR-132-3p, TUG1, and other target proteins were measured by RT quantitative PCR or Western blot analysis; cell viability by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay; apoptosis by annexin V and propidium iodide staining; the abundance of acetylated H3K9 or histone deacetylase 3 (HDAC3) within the promoter of target genes by chromatin immunoprecipitation; the direct interaction between miR-132-3p and HDAC3 or TUG1 by luciferase reporter assay. The biological significance of miR-132-3p, TUG1, and HDAC3 was assessed using miR-132-3p mimic, siRNA-targeting TUG1 and HDAC3 inhibitor RGF966, respectively, in H2O2-challenged cells in vitro or ischemia-reperfusion (I/R)-induced AMI in vivo. miR-132-3p was downregulated, whereas TUG1 upregulated in H2O2-challenged cardiomyocytes. Overexpressing miR-132-3p or knocking down TUG1 significantly improved viability, inhibited apoptosis, and reduced ROS production in H2O2-stressed cardiomyocytes in vitro and alleviated I/R-induced AMI in vivo. Mechanistically, TUG1 sponged miR-132-3p and upregulated HDAC3, which reduced the acetylation of H3K9 and epigenetically inhibited expressions of antioxidative genes, including Bcl-xL, Prdx2, and Hsp70. The TUG1/miR-132-3p/HDAC3 axis critically regulates ROS production and the pathogenic development of AMI. Targeting TUG1, upregulating miR-132-3p, or inhibiting HDAC3 may benefit AMI treatment. NEW & NOTEWORTHY Increased production of reactive oxygen species (ROS) significantly contributed to the pathogenesis of acute myocardial infarction (AMI). Recent studies suggest that hypoxia upregulated the long noncoding RNA taurine upregulated gene 1 (TUG1). However, the underlying mechanisms remain elusive. In the present study, we reported for the first time that H2O2 or ischemia-reperfusion-induced TUG1, by sponging microRNA 132-3p, activated histone deacetylase 3, which in turn targeted multiple protective genes, stimulated intracellular ROS accumulation, and aggravated the injury of AMI. Our findings might provide some insight to seek new targets for AMI treatment.

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TrpML-mediated astrocyte microdomain Ca2+ transients regulate astrocyte–tracheal interactions

eLife ◽

10.7554/elife.58952 ◽

2020 ◽

Vol 9 ◽

Author(s):

Zhiguo Ma ◽

Marc R Freeman

Keyword(s):

Reactive Oxygen Species ◽

Central Nervous System ◽

Gas Exchange ◽

Brain Function ◽

Ros Production ◽

Oxygen Species ◽

Membrane Microdomain ◽

The Central Nervous System ◽

Temporally Correlated

Astrocytes exhibit spatially-restricted near-membrane microdomain Ca2+transients in their fine processes. How these transients are generated and regulate brain function in vivo remains unclear. Here we show that Drosophila astrocytes exhibit spontaneous, activity-independent microdomain Ca2+ transients in their fine processes. Astrocyte microdomain Ca2+ transients are mediated by the TRP channel TrpML, stimulated by reactive oxygen species (ROS), and can be enhanced in frequency by the neurotransmitter tyramine via the TyrRII receptor. Interestingly, many astrocyte microdomain Ca2+ transients are closely associated with tracheal elements, which dynamically extend filopodia throughout the central nervous system (CNS) to deliver O2 and regulate gas exchange. Many astrocyte microdomain Ca2+ transients are spatio-temporally correlated with the initiation of tracheal filopodial retraction. Loss of TrpML leads to increased tracheal filopodial numbers, growth, and increased CNS ROS. We propose that local ROS production can activate astrocyte microdomain Ca2+ transients through TrpML, and that a subset of these microdomain transients promotes tracheal filopodial retraction and in turn modulate CNS gas exchange.

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In Vivo Imaging of Reactive Oxygen Species in Mouse Brain by using [3H]Hydromethidine as a Potential Radical Trapping Radiotracer

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2014.160 ◽

2014 ◽

Vol 34 (12) ◽

pp. 1907-1913 ◽

Cited By ~ 15

Author(s):

Kohji Abe ◽

Nozomi Takai ◽

Kazumi Fukumoto ◽

Natsumi Imamoto ◽

Misato Tonomura ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Production Model ◽

Whole Body ◽

Ros Production ◽

Oxygen Species ◽

Radical Trapping ◽

The Brain

To assess reactive oxygen species (ROS) production by detecting the fluorescent oxidation product, hydroethidine has been used extensively. The present study was undertaken to evaluate the potential of the hydroethidine derivative as a radiotracer to measure in vivo brain ROS production. [3H]-labeled N-methyl-2,3-diamino-6-phenyl-dihydrophenanthridine ([3H]Hydromethidine) was synthesized, and evaluated using in vitro radical-induced oxidization and in vivo brain ROS production model. In vitro studies have indicated that [3H]Hydromethidine is converted to oxidized products by a superoxide radical (O2• -) and a hydroxyl radical (OH• -) but not hydrogen peroxide (H2O2). In vivo whole-body distribution study showed that [3H]Hydromethidine rapidly penetrated the brain and then was washed out in normal mice. Microinjection of sodium nitroprusside (SNP) into the brain was performed to produce ROS such as OH• - via Fenton reaction. A significant accumulation of radioactivity immediately after [3H]Hydromethidine injection was seen in the side of the brain treated with SNP (5 and 20 nmol) compared with that in the contralateral side. These results indicated that [3H]Hydromethidine freely penetrated into the brain where it was rapidly converted to oxidized forms, which were trapped there in response to the production of ROS. Thus, [3H]Hydromethidine should be useful as a radical trapping radiotracer in the brain.

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Hypoxia-Associated Effects on Reactive Oxygen Species Generation by Human Acute Myeloid Leukemia Cells

Blood ◽

10.1182/blood.v118.21.4998.4998 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4998-4998 ◽

Cited By ~ 2

Author(s):

Megan K Johnson ◽

R Robert Vathanayagam ◽

Eunice S. Wang

Keyword(s):

Oxidative Stress ◽

Stress Responses ◽

Myeloid Leukemia ◽

Chronic Hypoxia ◽

Ros Generation ◽

Ros Production ◽

Oxygen Species ◽

Hypoxic Conditions ◽

Oxidative Stress Responses

Abstract Abstract 4998 Reactive oxygen species (ROS) reflective of oxidative stress response play conflicting roles in cancer biology and therapy. Elevated ROS levels have been implicated in carcinogenesis via DNA damaging effects and activation of pro-survival pathways. In acute myeloid leukemia (AML) patient samples, high ROS levels have been associated with increased risk of relapse and poorer survival following conventional chemotherapy. However, several agents with known anti-leukemic activity have also been shown to mediate anti-tumor effects by inducing oxidative stress in association with cancer cell apoptosis and death. Recent evidence has suggested that the marrow microenvironment harboring AML cells in vivo is characterized by intrinsic hypoxia. Here we asked if oxidative stress responses by AML cells were potentially altered under intrinsically hypoxic microenvironment conditions as well as following treatment with cytarabine and sorafenib. ROS generation was assessed via fluorescent flow cytometric measurements of CM-H2DCFDA in two human AML cell lines (HL60-VCR, HEL) cultured under normoxic (O2 21%) vs. hypoxic (O2 1%) conditions for up to 72 hours. Our results revealed higher levels of ROS production in AML cells (HEL, HL60-VCR) cultured under progressively longer periods of hypoxia up to 72 hours. To determine whether this effect was mediated by hypoxia inducible factor-1α (HIF-1α), a transcription factor involved in the hypoxic responses of both normal and cancer cells, ROS generation was measured in normoxic AML cells following treatment with the prolyl hydroxylase inhibitor DMOG which prevents HIF-1α degradation and results in HIF-1alpha protein overexpression. DMOG treatment (0.1-0.3 nM) of HEL and HL60 cells failed to alter ROS levels in patterns similar to what was observed under hypoxia, indicating that hypoxia-induced ROS production likely did not occur primarily via a HIF-1a dependent mechanism. Hypoxia-induced ROS production in AML cells also did not appear dependent on RAC1, a G-protein involved in the oxidative responses of normoxic AML cells and other normal hematopoietic cells. Next we examined the effects of cytarabine treatment on ROS generation by AML cells under differing oxygen conditions. Although short-term cytarabine treatment (up to 48 hours) was associated with mild oxidative stress in AML cells, we noted that cytarabine-treated AML cells exposed to 72 hours of hypoxia continued to exhibit ROS levels similar to those observed under normoxia. We then examined the effects of sorafenib, a receptor tyrosine kinase inhibitor previously reported to induce apoptosis of cancer cells via mitochondria-dependent oxidative stress responses, on AML cells. As compared with vehicle or cytarabine, sorafenib treatment was associated with markedly enhanced ROS production under normoxia; however, under chronic hypoxia, ROS generation by sorafenib was significantly abrogated to below baseline normoxia levels after 48–72 hours. These results suggest that a hypoxic marrow microenvironment may promote AML growth and therapy resistance in vivo via mediation of specific oxidative stress responses. Our data show that duration of chronic hypoxia progressively increased baseline ROS generation in AML cells and could explain the high levels of ROS found at relapsed AML samples. Moreover, our finding that attenuation of cytarabine/sorafenib-induced ROS generation occurred under the same prolonged hypoxic conditions where decreased chemotherapy-mediated cell death was noted (Hsu et al, ASH abstract 2010) implies a potential association between reduction in oxidative stress and therapeutic responses. As ROS generation under hypoxic conditions did not appear to be primarily mediated by HIF-1a or RAC1, further studies exploring the underlying pathways responsible for oxidative stress responses under chronic hypoxia in AML cells and primary patient samples are warranted. Disclosures: No relevant conflicts of interest to declare.

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TrpML-mediated astrocyte microdomain Ca2+ transients regulate astrocyte-tracheal interactions

10.1101/865659 ◽

2019 ◽

Cited By ~ 1

Author(s):

Zhiguo Ma ◽

Marc R. Freeman

Keyword(s):

Reactive Oxygen Species ◽

Central Nervous System ◽

Gas Exchange ◽

Brain Function ◽

Ros Production ◽

Oxygen Species ◽

Membrane Microdomain ◽

The Central Nervous System ◽

Temporally Correlated

AbstractAstrocytes exhibit spatially-restricted near-membrane microdomain Ca2+ transients in their fine processes. How these transients are generated and regulate brain function in vivo remains unclear. Here we show that Drosophila astrocytes exhibit spontaneous, activity-independent microdomain Ca2+ transients in their fine processes. Astrocyte microdomain Ca2+ transients are mediated by the TRP channel TrpML, stimulated by reactive oxygen species (ROS), and can be enhanced in frequency by the neurotransmitter tyramine via the TyrRII receptor. Interestingly, many astrocyte microdomain Ca2+ transients are closely associated with tracheal elements, which dynamically extend filopodia throughout the central nervous system (CNS) to deliver O2 and regulate gas exchange. Many astrocyte microdomain Ca2+ transients are spatio-temporally correlated with the initiation of tracheal filopodial retraction. Loss of TrpML leads to increased tracheal filopodial numbers, growth, and increased CNS ROS. We propose that local ROS production can activate astrocyte microdomain Ca2+ transients through TrpML, and that a subset of these microdomain transients promotes tracheal filopodial retraction and in turn modulate CNS gas exchange.

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