Abscisic acid and salinity stress induced somaclonal variation and increased histone deacetylase (HDAC) activity in Ananas comosus var. MD2

2017 ◽  
Vol 133 (1) ◽  
pp. 123-135 ◽  
Author(s):  
Nur Asniyati Abdul Halim ◽  
Boon Chin Tan ◽  
Mohd Razik Midin ◽  
Maria Madon ◽  
Norzulaani Khalid ◽  
...  
2003 ◽  
Vol 8 (1) ◽  
pp. 89-95 ◽  
Author(s):  
Birgit Heltweg ◽  
Manfred Jung

Histone deacetylases (HDACs) are important regulators of transcription, and their inhibitors are a promising class of anticancer agents. The methods for the determination of HDAC activity and its inhibition that are currently available suffer from various drawbacks, such as animal testing, radioactive substrates, or limited throughput. Therefore, a fast nonisotopic method for the measurement of HDAC activity is highly desirable. The authors present such an assay that relies on the fluorescent HDAC substrate developed previously in their group. After incubation of the substrate with the enzyme, a derivatization leads to efficient fluorescence quenching in the deacetylated metabolite. Thus, only the fluorescence emitted by the remaining substrate is detected, which allows for a convenient detection of HDAC activity in a homogeneous format that can be performed on multiwell plate readers. This procedure, called HDASH (histone deacetylase assay—homogeneous), should be a valuable tool in transcriptional research and especially drug discovery. ( Journal of Biomolecular Screening 2003:89-95)


2016 ◽  
Vol 57 (10) ◽  
pp. 2147-2160 ◽  
Author(s):  
Sang Y. Lee ◽  
Neville J. Boon ◽  
Alex A.R. Webb ◽  
Reiko J. Tanaka

2017 ◽  
Vol 91 (16) ◽  
Author(s):  
Jean-François Bolduc ◽  
Laurent Hany ◽  
Corinne Barat ◽  
Michel Ouellet ◽  
Michel J. Tremblay

ABSTRACT In this study, we investigated the effect of acetate, the most concentrated short-chain fatty acid (SCFA) in the gut and bloodstream, on the susceptibility of primary human CD4+ T cells to HIV-1 infection. We report that HIV-1 replication is increased in CD3/CD28-costimulated CD4+ T cells upon acetate treatment. This enhancing effect correlates with increased expression of the early activation marker CD69 and impaired class I/II histone deacetylase (HDAC) activity. In addition, acetate enhances acetylation of histones H3 and H4 and augments HIV-1 integration into the genome of CD4+ T cells. Thus, we propose that upon antigen presentation, acetate influences class I/II HDAC activity that transforms condensed chromatin into a more relaxed structure. This event leads to a higher level of viral integration and enhanced HIV-1 production. In line with previous studies showing reactivation of latent HIV-1 by SCFAs, we provide evidence that acetate can also increase the susceptibility of primary human CD4+ T cells to productive HIV-1 infection. IMPORTANCE Alterations in the fecal microbiota and intestinal epithelial damage involved in the gastrointestinal disorder associated with HIV-1 infection result in microbial translocation that leads to disease progression and virus-related comorbidities. Indeed, notably via production of short-chain fatty acids, bacteria migrating from the lumen to the intestinal mucosa could influence HIV-1 replication by epigenetic regulatory mechanisms, such as histone acetylation. We demonstrate that acetate enhances virus production in primary human CD4+ T cells. Moreover, we report that acetate impairs class I/II histone deacetylase activity and increases integration of HIV-1 DNA into the host genome. Therefore, it can be postulated that bacterial metabolites such as acetate modulate HIV-1-mediated disease progression.


2020 ◽  
Vol 79 ◽  
pp. 108339 ◽  
Author(s):  
Levi W. Evans ◽  
Abigail Bender ◽  
Leah Burnett ◽  
Luis Godoy ◽  
Yi Shen ◽  
...  

2002 ◽  
Vol 29 (5) ◽  
pp. 561 ◽  
Author(s):  
Grant R. Cramer

Increases in abscisic acid (ABA) concentrations in plant tissues correlate with growth inhibition in salt-stressed plants. Therefore, it was hypothesized that Arabidopsis ABA mutants different in, or insensitive to, ABA would respond differently than wild type (wt) to salinity stress. Seeds (wt, abi1-1, abi2-1, abi3-1, and aba1-3) were germinated and grown hydroponically in three separate experiments with different environmental conditions: relative humidity at 80 or 100%, day/night temperatures at 21/18 or 23/20˚C, and light intensity at 125, 200 or 350 μmol photons m–2 s-1. Plants were exposed to salinity (either 0, 40 and 80 mM NaCl or 1, 5, and 9 dS m–1 with a Na/Ca ratio of 10 depending on the experiment) for one to several weeks before harvesting. The effect of salinity on root elongation rates of young seedlings was measured as well. Two-way ANOVA of root elongation rates of young seedlings and the growth of 3-week old plants in hydroponic solutions indicated that salinity inhibited growth, increased ABA and Na concentrations, and reduced K concentrations in all genotypes tested. However, there were no significant interactions with salinity and genotype for root elongation rates, total dry weight, shoot ABA and K concentrations. Shoot Na concentrations were significantly higher in wt plants relative to other genotypes subjected to high salinity stress. aba1-3 had significantly lower ABA concentrations than other genotypes, but the interaction of aba1-3 with salinity was the same as other genotypes. The lack of difference in interaction between genotype and salinity indicates that all genotypes responded in the same manner and amount to salinity for the particular parameter measured. Therefore, it appears that there are no significant differences in growth in response to salinity between the ABA mutants (ABA-deficient and ABA-insensitive) and wt. However, in contrast to the other genotypes, some of the ABA-deficient plants, aba1-3, died when exposed to high salinity and high light intensity. ABA appears to provide a protective role in conditions of high salinity and high light intensity.


2002 ◽  
Vol 1 (4) ◽  
pp. 538-547 ◽  
Author(s):  
Dipnath Baidyaroy ◽  
Gerald Brosch ◽  
Stefan Graessle ◽  
Patrick Trojer ◽  
Jonathan D. Walton

ABSTRACT HC-toxin, a cyclic peptide made by the filamentous fungus Cochliobolus carbonum, is an inhibitor of histone deacetylase (HDAC) from many organisms. It was shown earlier that the HDAC activity in crude extracts of C. carbonum is relatively insensitive to HC-toxin as well as to the chemically unrelated HDAC inhibitors trichostatin and D85, whereas the HDAC activity of Aspergillus nidulans is sensitive (G. Brosch et al., Biochemistry 40:12855-12863, 2001). Here we report that HC-toxin-resistant HDAC activity was present in other, but not all, plant-pathogenic Cochliobolus species but not in any of the saprophytic species tested. The HDAC activities of the fungi Alternaria brassicicola and Diheterospora chlamydosporia, which also make HDAC inhibitors, were resistant. The HDAC activities of all C. carbonum isolates tested, except one non-toxin-producing isolate, were resistant. In a cross between a sensitive isolate and a resistant isolate, resistance genetically cosegregated with HC-toxin production. When fractionated by anion-exchange chromatography, extracts of resistant and sensitive isolates and species had two peaks of HDAC activity, one that was fully HC-toxin resistant and a second that was larger and sensitive. The first peak was consistently smaller in extracts of sensitive fungi than in resistant fungi, but the difference appeared to be insufficiently large to explain the differential sensitivities of the crude extracts. Differences in mRNA expression levels of the four known HDAC genes of C. carbonum did not account for the observed differences in HDAC activity profiles. When mixed together, resistant extracts protected extracts of sensitive C. carbonum but did not protect other sensitive Cochlibolus species or Neurospora crassa. Production of this extrinsic protection factor was dependent on TOXE, the transcription factor that regulates the HC-toxin biosynthetic genes. The results suggest that C. carbonum has multiple mechanisms of self-protection against HC-toxin.


1997 ◽  
Vol 39 (3) ◽  
pp. 453-456 ◽  
Author(s):  
S.S.M. Naqvi ◽  
S. Mumtaz ◽  
A. Shereen ◽  
M.A. Khan ◽  
A.H. Khan

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Skye Hsin-Hsien Yeh ◽  
Ming Hsien Lin ◽  
I. I. Leo Garcia Flores ◽  
Uday Mukhopadhyay ◽  
Danial Young ◽  
...  

Combining standard drugs with low doses of histone deacetylase inhibitors (HDACIs) is a promising strategy to increase the efficacy of chemotherapy. The ability of well-tolerated doses of HDACIs that act as chemosensitizers for platinum-based chemotherapeutics has recently been proven in many types and stages of cancer in vitro and in vivo. Detection of changes in HDAC activity/expression may provide important prognostic and predictive information and influence treatment decision-making. Use of [18F] FAHA, a HDAC IIa-specific radionuclide, for molecular imaging may enable longitudinal, noninvasive assessment of HDAC activity/expression in metastatic cancer. We evaluated the synergistic anticancer effects of cisplatin and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in xenograft models of nonsmall cell lung cancer (NSCLC) using [18F] FAHA and [18F] FDG PET/CT imaging. Cisplatin alone significantly increased [18F] FAHA accumulation and reduced [18F] FDG accumulation in H441 and PC14 xenografts; coadministration of cisplatin and SAHA resulted in the opposite effects. Immunochemical staining for acetyl-histone H3 confirmed the PET/CT imaging findings. Moreover, SAHA had a more significant effect on the acetylome in PC14 (EGFR exon 19 deletion mutation) xenografts than H441 (wild-type EGFR and KRAS codon 12 mutant) xenografts. In conclusion, [18F] FAHA enables quantitative visualization of HDAC activity/expression in vivo, thus, may represent a clinically useful, noninvasive tool for the management of patients who may benefit from synergistic anticancer therapy.


2019 ◽  
Vol 93 (12) ◽  
Author(s):  
Bratati Saha ◽  
Robin J. Parks

ABSTRACTHuman adenovirus (HAdV) causes minor illnesses in most patients but can lead to severe disease and death in pediatric, geriatric, and immunocompromised individuals. No approved antiviral therapy currently exists for the treatment of these severe HAdV-induced diseases. In this study, we show that the pan-histone deacetylase (HDAC) inhibitor SAHA reduces HAdV-5 gene expression and DNA replication in tissue culture, ultimately decreasing virus yield from infected cells. Importantly, SAHA also reduced gene expression from more virulent and clinically relevant serotypes, including HAdV-4 and HAdV-7. In addition to SAHA, several other HDAC inhibitors (e.g., trichostatin A, apicidin, and panobinostat) also affected HAdV gene expression. We determined that loss of class I HDAC activity, mainly HDAC2, impairs efficient expression of viral genes, and that E1A physically interacts with HDAC2. Our results suggest that HDAC activity is necessary for HAdV replication, which may represent a novel pharmacological target in HAdV-induced disease.IMPORTANCEAlthough human adenovirus (HAdV) can cause severe diseases that can be fatal in some populations, there are no effective treatments to combat HAdV infection. In this study, we determined that the pan-histone deacetylase (HDAC) inhibitor SAHA has inhibitory activity against several clinically relevant serotypes of HAdV. This U.S. Food and Drug Administration-approved compound affects various stages of the virus lifecycle and reduces virus yield even at low concentrations. We further report that class I HDAC activity, particularly HDAC2, is required for efficient expression of viral genes during lytic infection. Investigation of the mechanism underlying SAHA-mediated suppression of HAdV gene expression and replication will enhance current knowledge of virus-cell interaction and may aid in the development of more effective antivirals with lower toxicity for the treatment of HAdV infections.


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