PMA-induced dissociation of Ku86 from the promoter causes transcriptional up-regulation of histamine H1 receptor

Mizuguchi, Hiroyuki; Miyagi, Kohei; Terao, T.; Sakamoto, Noriko; Yamawaki, Yosuke; Adachi, Tsubasa; Ono, Shohei; Sasaki, Yohei; Yoshimura, Yoshiyuki; Kitamura, Yoshiaki; Takeda, Noriaki; Fukui, Hirokazu

doi:10.1038/srep00916

Cited by 25 publications

(12 citation statements)

References 53 publications

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“…This observation is in agreement with the data showing that inhibition of PKC signaling by the pan PKC inhibitor GF109203X led to a significant increase in H 2 O 2 -induced PAR formation. Indeed, PKC has been previously shown to phosphorylate ARTD1 in vitro ( 38 ) and its inhibition resulted in increased PAR induction upon alkylation stress ( 37 ), while there are also studies that have reported a positive regulation of ARTD1 by PKCδ in response to histamine ( 39 , 75 ). Thus, reported studies so far have identified two seemingly opposing (positively and negatively), Ca 2+ -dependent and -independent regulatory mechanisms for PAR formation upon H 2 O 2 -induced oxidative stress within the PKC family of proteins in human primary fibroblasts as well as in murine NIH/3T3 cells and MEFs.…”

Section: Discussionmentioning

confidence: 99%

PKCα and HMGB1 antagonistically control hydrogen peroxide-induced poly-ADP-ribose formation

et al. 2016

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Harmful oxidation of proteins, lipids and nucleic acids is observed when reactive oxygen species (ROS) are produced excessively and/or the antioxidant capacity is reduced, causing ‘oxidative stress’. Nuclear poly-ADP-ribose (PAR) formation is thought to be induced in response to oxidative DNA damage and to promote cell death under sustained oxidative stress conditions. However, what exactly triggers PAR induction in response to oxidative stress is incompletely understood. Using reverse phase protein array (RPPA) and in-depth analysis of key stress signaling components, we observed that PAR formation induced by H2O2 was mediated by the PLC/IP3R/Ca2+/PKCα signaling axis. Mechanistically, H2O2-induced PAR formation correlated with Ca2+-dependent DNA damage, which, however, was PKCα-independent. In contrast, PAR formation was completely lost upon knockdown of PKCα, suggesting that DNA damage alone was not sufficient for inducing PAR formation, but required a PKCα-dependent process. Intriguingly, the loss of PAR formation observed upon PKCα depletion was overcome when the chromatin structure-modifying protein HMGB1 was co-depleted with PKCα, suggesting that activation and nuclear translocation of PKCα releases the inhibitory effect of HMGB1 on PAR formation. Together, these results identify PKCα and HMGB1 as important co-regulators involved in H2O2-induced PAR formation, a finding that may have important relevance for oxidative stress-associated pathophysiological conditions.

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Section: Discussionmentioning

confidence: 99%

PKCα and HMGB1 antagonistically control hydrogen peroxide-induced poly-ADP-ribose formation

et al. 2016

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“…These compounds also inhibit the phosphorylation of Tyr 311 on PKC δ (Mizuguchi et al. ; Hattori et al. ).…”

Section: Discussionmentioning

confidence: 99%

Maackiain is a novel antiallergic compound that suppresses transcriptional upregulation of the histamine H₁ receptor and interleukin‐4 genes

Mizuguchi

Nariai

Kato

et al. 2015

Pharmacology Res & Perspec

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Kujin contains antiallergic compounds that inhibit upregulation of histamine H1 receptor (H1R) and interleukin (IL)-4 gene expression. However, the underlying mechanism remains unknown. We sought to identify a Kujin-derived antiallergic compound and investigate its mechanism of action. The H1R and IL-4 mRNA levels were determined by real-time quantitative RT-PCR. To investigate the effects of maackiain in vivo, toluene-2,4-diisocyanate (TDI)-sensitized rats were used as a nasal hypersensitivity animal model. We identified (−)-maackiain as the responsible component. Synthetic maackiain showed stereoselectivity for the suppression of IL-4 gene expression but not for H1R gene expression, suggesting distinct target proteins for transcriptional signaling. (−)-Maackiain inhibited of PKCδ translocation to the Golgi and phosphorylation of Tyr311 on PKCδ, which led to the suppression of H1R gene transcription. However, (−)-maackiain did not show any antioxidant activity or inhibition of PKCδ enzymatic activity per se. Pretreatment with maackiain alleviated nasal symptoms and suppressed TDI-induced upregulations of H1R and IL-4 gene expressions in TDI-sensitized rats. These data suggest that (−)-maackiain is a novel antiallergic compound that alleviates nasal symptoms in TDI-sensitized allergy model rats through the inhibition of H1R and IL-4 gene expression. The molecular mechanism underlying its suppressive effect for H1R gene expression is mediated by the inhibition of PKCδ activation.

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“…There are numerous studies showing the participation of Ku protein in the transcription regulation of cellular and viral genes [40,[78][79][80][81][82][83][84], and it is supposed that there is a specific mechanism of Ku-dependent regulation for each particular gene. Among the mechanisms proposed, there is no either involving the interaction of Ku with RNA, but we cannot completely rule out such a possibility.…”

Section: Interactions Of Ku With Protein Components Of the 7sk Ribonumentioning

confidence: 99%

Analysis of RNA binding properties of human Ku protein reveals its interactions with 7SK snRNA and protein components of 7SK snRNP complex

et al. 2020

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PMA-induced dissociation of Ku86 from the promoter causes transcriptional up-regulation of histamine H1 receptor

Cited by 25 publications

References 53 publications

PKCα and HMGB1 antagonistically control hydrogen peroxide-induced poly-ADP-ribose formation

PKCα and HMGB1 antagonistically control hydrogen peroxide-induced poly-ADP-ribose formation

Maackiain is a novel antiallergic compound that suppresses transcriptional upregulation of the histamine H₁ receptor and interleukin‐4 genes

Analysis of RNA binding properties of human Ku protein reveals its interactions with 7SK snRNA and protein components of 7SK snRNP complex

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PMA-induced dissociation of Ku86 from the promoter causes transcriptional up-regulation of histamine H1 receptor

Cited by 25 publications

References 53 publications

PKCα and HMGB1 antagonistically control hydrogen peroxide-induced poly-ADP-ribose formation

PKCα and HMGB1 antagonistically control hydrogen peroxide-induced poly-ADP-ribose formation

Maackiain is a novel antiallergic compound that suppresses transcriptional upregulation of the histamine H1 receptor and interleukin‐4 genes

Analysis of RNA binding properties of human Ku protein reveals its interactions with 7SK snRNA and protein components of 7SK snRNP complex

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Maackiain is a novel antiallergic compound that suppresses transcriptional upregulation of the histamine H₁ receptor and interleukin‐4 genes