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Nanotechnology-Mediated Strategy for the Treatment of Neuropathic Pain
Published in Cherry Bhargava, Amit Sachdeva, Nanotechnology, 2020
Pankaj Prashar, Ankita Sood, Anamika Gautam, Pardeep Kumar Sharma, Bimlesh Kumar, Indu Melkani, Sakshi Panchal, Sachin Kumar Singh, Monica Gulati, Narendra Kumar Pandey, Linu Dash, Anupriya, Varimadugu Bhanukirankumar Reddy
Histone deacetylase enzymes (HDAC) together with histone acetyltransferase (HAT) regulate the acetylation cycle of histone lysine residues (like lysine residue9), that further amplify transcription, expression and also facilitate transcriptional elongation. Histone acetylation is among the epigenetic pathways which are believed to trigger NP, the reasons for which are mainly focused on impaired transcriptional function (Khangura et al. 2017). Histone deacetylase 4 is gradually released as a consequence of spinal nerve ligation in rats. Histone deacetylase 4 inhibition, utilizing LMK 235, stopped allodynia. A rise in histone deacetylase 1 and reduction in histone (H3) acetylation has been shown in the spinal nerve ligation model (Elsherbiny et al. 2019; Zhao and Wu 2018). Treatment with baicalin (anti-inflammatory flavonoid) greatly decreased production of deacetylase 1 and reverse pain response. Nerve disruption can be speculated to contribute to epigenetic modifications attributable to the stimulation of histone-deacetylase enzymes. This can reduce histone acetylation induction, and inhibitors of histone-deacetylase can be used to prevent NP (Z. Li et al. 2019; Van Helleputte 2018).
Epigenetic control of cell fate and behavior
Published in David M. Gardiner, Regenerative Engineering and Developmental Biology, 2017
Acetylation of histones is nearly always associated with genes that are actively transcribed. The most commonly studied sites of acetylation are on lysine residues of histones 3 and 4. Lysine is a positively charged amino acid, which facilitates binding with negatively charged DNA. The acetylation of lysine effectively neutralizes the positive charge and weakens the affinity of DNA for the histone (Struhl 1998). In doing so, the DNA becomes more accessible to positively regulating transcription factors and, in some cases, recruits the transcription factors directly. Enzymes known as histone acetyltransferases (HATs) perform the placement of acetyl groups on histones, and the removal of acetyl groups is performed by histone deacetylases (HDACs).
Epigenetic and Metabolic Alterations in Cancer Cells: Mechanisms and Therapeutic Approaches
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Aberrant histone acetylation has been consistently associated with tumorigenesis. Histone acetylation diminishes the electrostatic repulsion between DNA and histones, leading to an open chromatin structure permissive for gene transcription (Grunstein, 1997). Histone acetylation is regulated by the opposing actions of histone acetyltransferases (HATs) and deacetylases (HDACs). Overexpression of HDACs, in particular, has been detected in multiple cancers (Glozak and Seto, 2007). HDACs are thought to promote histone deacetylation and transcriptionally repress the expression of tumor suppressor genes (Kim et al., 2001; Zhang et al., 2003). Key tumor suppressor genes, including p21WAF1, E-cadherin, and others, have been shown to be silenced by HDACs in cancers (Aghdassi et al., 2012; Wilson et al., 2006). Apart from acetylation, histone methylation is another histone modification that has an impact on gene expression. Up to 19 lysine residues on Histone H3 can be methylated, and each of these lysine residues can be mono-, di-, or tri-methylated, thus giving rise to a highly complex histone code (Greer and Shi, 2012). Histone methylation is also tightly regulated through the action of methyltransferases and demethylases. Much remains to be understood with regard to the effect of aberrant histone methylation on cancer development, but it is clear that this will be methylation site-specific and context dependent. A well-known example is the H3K79 histone methyltransferase DOT1-like (DOT1L) protein, whose mistargeting triggers aberrant H3K79 methylation at homeobox genes in MLL re-arranged leukemia (Bernt et al., 2011; Onder et al., 2012). Therapeutic agents targeting histone acetylation or methylation have been under active development. HDAC inhibitors (HDACi) have been put forward for cancer therapy, based on the premise that HDACi might reverse HDAC-mediated repression of tumor suppressor genes. HDACi such as Vorinostat and Romidepsin have been approved for the treatment of cutaneous T cell lymphoma (CTCL) and HDACi are undergoing Phase II/III clinical trials for CTCL, and solid tumors (Moskowitz and Horwitz, 2017). Drugs targeting DOT1L (Pinometostat, EPZ-5676) have been described, showing dramatic effects in preclinical models of MLL-rearranged leukemia and is currently undergoing phase I/II trials.
Benzo[a]pyrene osteotoxicity and the regulatory roles of genetic and epigenetic factors: A review
Published in Critical Reviews in Environmental Science and Technology, 2022
Jiezhang Mo, Doris Wai-Ting Au, Jiahua Guo, Christoph Winkler, Richard Yuen-Chong Kong, Frauke Seemann
Histone modification can also regulate gene expression epigenetically. Notably, DNA is complexed with histones, which results in its compaction and assembly into nucleosomes of the chromatin. Histone modifications are heavily involved in the regulation of gene transcription, DNA replication and DNA repair, and modifications that occur on accessible histone tails, which regulate the chromatin structure (Bártová et al., 2008). In addition to well-characterized histone modifications, including acetylation, methylation, phosphorylation, and ubiquitylation modification (Lennartsson & Ekwall, 2009), recent studies have identified new types of histone modifications, such as propionylation, butyrylation, malonylation and glycosylation (Wang et al., 2019). Specifically, histone acetyltransferases (HATs) and histone deacetylases (HDACs) are responsible for the acetylation and deacetylation of histones, respectively (Lennartsson & Ekwall, 2009). The deacetylation of histones (hyperacetylated histones) leads to uncompressed chromatin and increased accessibility of DNA binding, which facilitates gene transcription. In contrast, the acetylation of histones (hypoacetylated histones) results in condensed chromatin and transcription repression. Additionally, the methylation and demethylation of histones are catalyzed by lysine methyltransferases and arginine methyltransferases, respectively (Bártová et al., 2008).
Time-concentration-dependent profile of histone modifications on human hepatocytes treated by trichloroacetic acid
Published in International Journal of Environmental Health Research, 2022
Xinyue Peng, Susu Yu, Hui Lin, Fan Wu, Jiani Yang, Cheng Zhou, Luyun Zhang, Jianping Yang, Wenjuan Zhang
In normal cells, histone acetylation keeps balance by HDACs and histone acetyltransferases (HATs). HADCs usually remove acetyl groups from DNA-binding histone proteins, which is associated with repressive effects on gene expression. HDACs are involved in physiological processes such as development and cellular homeostasis, and play an important role in pathological scenarios (Milazzo et al. 2020). PCAF is one of a HATs, which mainly acetylates H3 histones and is strongly related to the initiation and development of tumors. And it also involves in a variety of metabolic and pathogenic of hepatopathy (Wang et al. 2018). Therefore, it is of great significance to maintain the normal expression of HDACs and HATs.