HDAC inhibitor prevents LPS mediated inhibition of CYP19A1 expression and 17β-estradiol production in granulosa cells

Mehta, Anu; Ravinder,; Onteru, Suneel Kumar; Singh, Dheer

doi:10.1016/j.mce.2015.07.002

Cited by 25 publications

(23 citation statements)

References 51 publications

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“…(53,59) and also various transcription factors. Our studies and several other studies indicate the possible evidence of the expression of TLR4 on granulosa cells (7). LPS, through TLR4, activated the pro-inflammatory cytokines production and thus modulated the primary functions of granulosa cells, such as steroidogenesis (6,7).…”

Section: Uterine Infections Lead To Ovarian Dysfunctionsupporting

confidence: 68%

“…HDACi are known for the ability to reverse the LPS mediated down regulation of CYP19 gene. Experiments using Trichosanthin A (TSA), a HDACi, have observed that TSA attenuated LPS induced immune response, and thus could prevent the negative effects of LPS on CYP19A1 expression and estradiol synthesis in buffalo GCs (7).…”

Section: Hdaci and Its Therapeutics Applicationmentioning

confidence: 99%

“…Bacterial endotoxins, DNA and lipids are known to initiate a signaling cascade in host cells via Toll-like receptors (TLR4), resulting in the production of various pro-inflammatory cytokines, chemokines, anti-microbial peptides and various transcription factors. Activation of pro-inflammatory cytokines as a result of TLR response was reported to modulate the primary function of granulosa cells, such as steroidogenesis (6,7). Such changes could slow down the follicular development and lead to ovarian dysfunction.…”

Section: Introductionmentioning

confidence: 99%

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Histone deacetylase A potential therapeutic target for ovarian dysfunction

et al. 2018

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Post-partum uterine disorders and reproductive tract infections cause ovarian dysfunction and infertility. Histone deacetylases (HDACs) prevent the relaxation of chromatin, and positively or negatively regulate transcription. Hence, HDACs play a pivotal role in altering the gene expression that impact different signalling pathways underling ovarian dysfunction. Thus, HDAC inhibitors (HDACi) may act as potential therapeutic targets in the treatment of an array of disorders impacting ovarian function.

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Section: Uterine Infections Lead To Ovarian Dysfunctionsupporting

confidence: 68%

Section: Hdaci and Its Therapeutics Applicationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Histone deacetylase A potential therapeutic target for ovarian dysfunction

et al. 2018

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“…The transient increase in pro-inflammatory cytokines was associated with HDACs. Trichostatin A (TSA) ( Table 2 ), a HDAC inhibitor, can attenuate LPS-induced pro-inflammatory cytokine gene expression and can prevent LPS-mediated downregulation of CYP19A1 expression and E2 in GCs [ 200 ].…”

Section: Pharmacoepigeneticsmentioning

confidence: 99%

Epigenetics of Aging and Alzheimer’s Disease: Implications for Pharmacogenomics and Drug Response

Cacabelos

Torrellas

2015

IJMS

104

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Epigenetic variability (DNA methylation/demethylation, histone modifications, microRNA regulation) is common in physiological and pathological conditions. Epigenetic alterations are present in different tissues along the aging process and in neurodegenerative disorders, such as Alzheimer’s disease (AD). Epigenetics affect life span and longevity. AD-related genes exhibit epigenetic changes, indicating that epigenetics might exert a pathogenic role in dementia. Epigenetic modifications are reversible and can potentially be targeted by pharmacological intervention. Epigenetic drugs may be useful for the treatment of major problems of health (e.g., cancer, cardiovascular disorders, brain disorders). The efficacy and safety of these and other medications depend upon the efficiency of the pharmacogenetic process in which different clusters of genes (pathogenic, mechanistic, metabolic, transporter, pleiotropic) are involved. Most of these genes are also under the influence of the epigenetic machinery. The information available on the pharmacoepigenomics of most drugs is very limited; however, growing evidence indicates that epigenetic changes are determinant in the pathogenesis of many medical conditions and in drug response and drug resistance. Consequently, pharmacoepigenetic studies should be incorporated in drug development and personalized treatments.

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“…Inflammatory burden is a primary cellular event in many liver diseases, and IL-6 is a major proinflammatory cytokines ( Azher et al, 2017 ; Prystupa et al, 2017 ). We and other investigators clarify that this very cytokine downregulated genes involved in drug elimination ( Yang et al, 2007 ; Mehta et al, 2015 ; Kawauchi et al, 2016 ). In this study we used primary hepatocytes (human and mouse) as well as cell line and demonstrated that IL-6 induced DEC1, enhanced DEC1 interaction with RXRα and suppressed the expression of PXR, CAR and their target genes: CYP2B6, CYP3A4, and MDR1.…”

Section: Discussionmentioning

confidence: 51%

Interleukin-6 Induces DEC1, Promotes DEC1 Interaction with RXRα and Suppresses the Expression of PXR, CAR and Their Target Genes

Ning

Zhan

et al. 2017

Front. Pharmacol.

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Inflammatory burden is a primary cellular event in many liver diseases, and the overall capacity of drug elimination is decreased. PXR (pregnane X receptor) and CAR (constitutive androstane receptor) are two master regulators of genes encoding drug-metabolizing enzymes and transporters. DEC1 (differentiated embryonic chondrocyte-expressed gene 1) is a ligand-independent transcription factor and reportedly is induced by many inflammatory cytokines including IL-6. In this study, we used primary hepatocytes (human and mouse) as well as HepG2 cell line and demonstrated that IL-6 increased DEC1 expression and decreased the expressions of PXR, CAR, and their target genes. Overexpression of DEC1 had similar effect as IL-6 on the expression of these genes, and knockdown of DEC1 reversed their downregulation by IL-6. Interestingly, neither IL-6 nor DEC1 altered the expression of RXRα, a common dimerization partner for many nuclear receptors including PXR and CAR. Instead, DEC1 was found to interact with RXRα and IL-6 enhanced the interaction. These results conclude that DEC1 uses diverse mechanisms of action and supports IL-6 downregulation of drug-elimination genes and their regulators.

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HDAC inhibitor prevents LPS mediated inhibition of CYP19A1 expression and 17β-estradiol production in granulosa cells

Cited by 25 publications

References 51 publications

Histone deacetylase A potential therapeutic target for ovarian dysfunction

Histone deacetylase A potential therapeutic target for ovarian dysfunction

Epigenetics of Aging and Alzheimer’s Disease: Implications for Pharmacogenomics and Drug Response

Interleukin-6 Induces DEC1, Promotes DEC1 Interaction with RXRα and Suppresses the Expression of PXR, CAR and Their Target Genes

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