A Nitric Oxide-dependent Cross-talk between Class I and III Histone Deacetylases Accelerates Skin Repair

Spallotta, Francesco; Cencioni, Chiara; Straino, Stefania; Nanni, Simona; Rosati, Jessica; Artuso, Simona; Manni, Isabella; Colussi, Claudia; Piaggio, Giulia; Martelli, Fabio; Valente, Sérgio; Mai, Antonello; Capogrossi, Maurizio C.; Farsetti, Antonella; Gaetano, Carlo

doi:10.1074/jbc.m112.441816

Cited by 80 publications

(83 citation statements)

References 26 publications

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“…Quantitative measurements of different gene levels were obtained using Step One Plus real time PCR (Applied Biosystems) as described previously (11,28). The expression of mouse GAPDH mRNA was used as internal control for heart or HL-1 cells, and mRNA expression of human GAPDH was used as internal control for human cardiac fibroblast cells.…”

Section: The Generation Of Casz1mentioning

confidence: 99%

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Essential Role of the Zinc Finger Transcription Factor Casz1 for Mammalian Cardiac Morphogenesis and Development

Liu

et al. 2014

Journal of Biological Chemistry

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Section: The Generation Of Casz1mentioning

confidence: 99%

“…Western Blot-Western blot was performed as previously described (13,28). In brief, to extract protein from heart, whole hearts were dissected from E14.5 embryos and dissolved in radioimmune precipitation assay buffer.…”

Section: The Generation Of Casz1mentioning

confidence: 99%

Essential Role of the Zinc Finger Transcription Factor Casz1 for Mammalian Cardiac Morphogenesis and Development

Liu

et al. 2014

Journal of Biological Chemistry

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“…On the other hand, class I histone deacetylase (HDAC2), which is the only member of this class known to be S-nitrosylated directly by NO inhibits the expression of growth factors such as epidermal growth factor (EGF) by attaching the promoter regions. These suggest that post-translational S-nitrosylation of HDAC2 leads to enhance the production of growth factors by detachment of HDAC2 from the promoter regions [43] . Consequently, SIRT-dependent NO production enhances wound closure by evocation of keratinocyte proliferation.…”

Section: Acute Woundsmentioning

confidence: 99%

Sirtuins in wound healing

Aioi

2017

Trends Immunother

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Sirtuins (SIRTs) are initially recognized as NAD + -dependent histone deacetylase. SIRTs attract attention for their role as calorie restriction-induced "longevity proteins" to be expected to extend human life span and to promote health. As advancing studies, SIRTs have been recognized as cell signaling regulators which contribute to anti-inflammation, cell differentiation and so on. Therefore, SIRTs are supposed to affect wound healing which is comprised highly orchestrated complex four phases: hemostasis, inflammation, tissue formation and tissue remodeling. This review highlights the roles of SIRTs in wound healing process and provides a foundation and impetus for future basic and clinical research.

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“…The importance of NO during wound healing is well-known, 21,22 and we recently demonstrated the role of Class I DIs during skin repair processes. 15 Local administration of DIs within the wound promoted the release of specific growth factors (GFs) including Fibroblast Growth Factor 10 (FGF10), Epidermal Growth Factor (EGF), and Insulin Growth Factor I (IGF-I) from activated keratinocyte, thus accelerating wound closure. 15 In the light of these findings, we have developed a new class of hybrid drugs in which MS-275 (1, Entinostat; pyridin-3-ylmethyl 4-(2-aminophenylcarbamoyl)benzylcarbamate), 23 a moderately selective Class I DIs, was joined to different NOdonor substructures.…”

mentioning

confidence: 99%

“…15 Local administration of DIs within the wound promoted the release of specific growth factors (GFs) including Fibroblast Growth Factor 10 (FGF10), Epidermal Growth Factor (EGF), and Insulin Growth Factor I (IGF-I) from activated keratinocyte, thus accelerating wound closure. 15 In the light of these findings, we have developed a new class of hybrid drugs in which MS-275 (1, Entinostat; pyridin-3-ylmethyl 4-(2-aminophenylcarbamoyl)benzylcarbamate), 23 a moderately selective Class I DIs, was joined to different NOdonor substructures. This letter reports the synthesis, structural characterization and biochemical profile of (6-(((3-cyanofuroxan-4-yl)methyl)(methylamino)methyl)pyridin-3-yl)methyl(4-((2-aminophenylcarbamoyl)benzyl))carbamate 2 (NO-MS275), the first example of this class of products.…”

mentioning

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Synthesis and Biological Evaluation of the First Example of NO-Donor Histone Deacetylase Inhibitor

Borretto

Lazzarato

Spallotta

et al. 2013

ACS Med. Chem. Lett.

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The NO-donor histone deacetylase inhibitor 2, formally obtained by joining Entinostat 1, a moderately selective Class I histone deacetylases (HDACs) inhibitor, to a 4-(methylaminomethyl)furoxan-3-carbonitrile scaffold, is described and its preliminary biological profile discussed. This hybrid regulates Classes I and II HDACs. Nitric oxide (NO) released by the compound activates soluble guanylate cyclase (sGC), causing Class II nuclear shuttling and chromatin modifications, with consequences on gene expression. The hybrid affects a number of micro-RNAs not modulated by its individual components; it promotes myogenic differentiation, inducing the formation of larger myotubes with significantly more nuclei per fiber, in a more efficient manner than the 1:1 mixture of its two components. The hybrid is an example of a new class of NO-donor HDACs now being developed, which should be of interest for treating a number of diseases. KEYWORDS: HDAC, histone deacetylase inhibitors, NO-donor, multitarget drugs, epigenetics H istone deacetylases (HDACs) are a family of epigenetic enzymes that catalyze the hydrolysis of acetylated ε-amino groups of Lys in H3 and H4 histone tails. 1 Removal of the acetyl groups restores the positive charge of Lys residues, enabling them to interact with the negative phosphate groups of DNA, with consequent chromatin tightness and transcriptional repression. 2 The converse occurs under the action of another family of enzymes, the histone acetyltransferases (HATs), which catalyze the transfer of acetyl groups from acetyl-CoA to lysine residues in H3 and H4 histone tails inducing DNA unwinding and chromatin decondensation, with potential transcriptional activation.Human HDACs are a family of 18 enzymes grouped into four classes (I, II, III, and IV). 3 Class III HDACs, also known as "sirtuins", are NAD-dependent deacetylase enzymes, whereas Classes I, II, and IV are zinc-dependent metalloproteins. Class I HDACs comprise HDAC1, 2, 3, and 8, which have conserved structure and similar functions, but rather different distributions: HDAC1 and 2 are mostly nuclear, while HDAC3 and HDAC8 are tissue-specific and present either in the nuclear or in the cytoplasmatic compartments. 1,3−5 Class II HDACs are more structurally complex, and their functions are not yet clear. Class II is further divided into subclasses IIa (HDAC4, 5, 7, and 9) and IIb (HDAC6 and 10). The members of Class II are localized in the cytosol when they are phosphorylated, whereas their dephosphorylation enables them to translocate into the nucleus (nuclear shuttling) with consequent histone deacetylation and gene repression. 6 HDAC11, a poorly characterized enzyme, is the sole member of class IV and is primarily nuclear. Lastly, the members of Class III (the sirtuins) show no homology with the other classes and preferentially deacetylate nonhistone substrates. 7 Nitric oxide (NO) is a well-known gaseous molecule that plays very important roles in mammalian physiology and pathophysiology. In the cardiovascular system, NO contrib...

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A Nitric Oxide-dependent Cross-talk between Class I and III Histone Deacetylases Accelerates Skin Repair

Cited by 80 publications

References 26 publications

Essential Role of the Zinc Finger Transcription Factor Casz1 for Mammalian Cardiac Morphogenesis and Development

Essential Role of the Zinc Finger Transcription Factor Casz1 for Mammalian Cardiac Morphogenesis and Development

Sirtuins in wound healing

Synthesis and Biological Evaluation of the First Example of NO-Donor Histone Deacetylase Inhibitor

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