Clenbuterol upregulates histone demethylase JHDM2a via the β2-adrenoceptor/cAMP/PKA/p-CREB signaling pathway

Li, Yang; He, Jin; Sui, Shunchao; Hu, Xiaoxiang; Zhao, Yaofeng; Li, Ning

doi:10.1016/j.cellsig.2012.07.010

Cited by 18 publications

(17 citation statements)

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“…Previous studies have observed deficiencies in adrenergic signaling in central respiratory centers (13,34), which are related to alterations in cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), and cAMP response element-binding protein (CREB) phosphorylation (35) that are downstream of β2-adrenergic receptor signaling (29,36). Consistent with relatively normal early development, no significant changes in respiratory frequency were observed at 4 wk (Fig.…”

Section: Resultsmentioning

confidence: 69%

“…Furthermore, it has been proposed that respiratory brainstem networks have a disruption in cAMP/PKA/CREB signaling (35). Because β2-adrenergic receptor activation engages the same molecular pathway (29,36), it could be related to clenbuterol's positive effect on respiratory function. In addition, treatment with desipramine, which inhibits the reuptake of adrenaline and serotonin, has proven effective in restoring respiratory function (49).…”

Section: Discussionmentioning

confidence: 99%

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β2-Adrenergic receptor agonist ameliorates phenotypes and corrects microRNA-mediated IGF1 deficits in a mouse model of Rett syndrome

Mellios

Woodson

Garcia

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Rett syndrome is a severe childhood onset neurodevelopmental disorder caused by mutations in methyl-CpG-binding protein 2 (MECP2), with known disturbances in catecholamine synthesis. Here, we show that treatment with the β2-adrenergic receptor agonist clenbuterol increases survival, rescues abnormalities in respiratory function and social recognition, and improves motor coordination in young male Mecp2-null (Mecp2 −/y ) mice. Importantly, we demonstrate that short-term treatment with clenbuterol in older symptomatic female heterozygous (Mecp2 −/+ ) mice rescues respiratory, cognitive, and motor coordination deficits, and induces an anxiolytic effect. In addition, we reveal abnormalities in a microRNA-mediated pathway, downstream of brain-derived neurotrophic factor that affects insulin-like growth factor 1 (IGF1) expression in Mecp2 −/y mice, and show that treatment with clenbuterol restores the observed molecular alterations. Finally, cotreatment with clenbuterol and recombinant human IGF1 results in additional increases in survival in male null mice. Collectively, our data support a role for IGF1 and other growth factor deficits as an underlying mechanism of Rett syndrome and introduce β2-adrenergic receptor agonists as potential therapeutic agents for the treatment of the disorder.let-7f | LIN28A

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Section: Resultsmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

β2-Adrenergic receptor agonist ameliorates phenotypes and corrects microRNA-mediated IGF1 deficits in a mouse model of Rett syndrome

Mellios

Woodson

Garcia

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Recently, Li et al . () reported that clenbuterol upregulates the H3K9‐specific demethylase Jhdm2a (JmjC‐containing H3K9 demethylase), which epigenetically regulates metabolic gene expression in porcine LLC‐PK1 cells and human 293 T cells. However, in chickens clenbuterol injections did not affect avian Jhdm2a mRNA expression in the skeletal muscle (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Epigenetic regulation may be one possible explanation for these findings, because this process can switch genes on and off by DNA methylation or histone modification (Simmons 2008). Recently, Li et al (2012) reported that clenbuterol upregulates the H3K9-specific demethylase Jhdm2a (JmjC-containing H3K9 demethylase), which epigenetically regulates metabolic gene expression in porcine LLC-PK1 cells and human 293 T cells. However, in chickens clenbuterol injections did not affect avian Jhdm2a mRNA expression in the skeletal muscle (Fig.…”

Section: Resultsmentioning

confidence: 99%

Single injection of clenbuterol into newly hatched chicks decreases abdominal fat pad weight in growing broiler chickens

Ijiri

Ishitani

El-Deep

et al. 2015

Animal Science Journal

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The aim of the current study was to examine the effects of clenbuterol injection into newly hatched chicks on both the abdominal fat pad tissue weight and the skeletal muscle weight during subsequent growth. Twenty-seven 1-day-old chicks were divided into two groups, receiving either a single intraperitoneal (i.p.) injection of clenbuterol (0.1 mg/kg body weight) or phosphate-buffered saline (PBS). Body weight gain, feed intake and feed conversion ratio were not affected by clenbuterol injection during the 5-week experimental period, while the abdominal fat pad tissue weight of the clenbuterol-injected chicks was lower than that of the control chicks at 5 weeks post-injection. Plasma non-esterified fatty acid concentrations were significantly increased in the clenbuterol-injected chicks, while plasma triacylglycerol concentrations did not differ. Additionally, the enzymatic activity of fatty acid synthase was lower in the liver of the clenbuterol-injected chicks. Conversely, the skeletal muscle weights were not affected by clenbuterol injection. These results suggest that a single clenbuterol injection into 1-day-old chicks decreases the abdominal fat pad tissue weight, but may not affect skeletal muscle weights during growth. © 2015 Japanese Society of Animal Science.

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“…Interestingly, an interaction between AR activation and epigenetic modulation has been revealed. Acute β AR/PKA activation protects against hypertrophic signaling by delaying Gq-mediated transcriptional activation via HDAC5 nuclear export, and upstream histone demethylase JHDM2a [76]. The expression of α1D ARs is under control of the methylation-dependent disruption of Sp1 binding in a cell-specific manner [77].…”

Section: Epigenetic Modification Of Drg Neuronal Genes: Etiological Cmentioning

confidence: 99%

Epigenetic modification of DRG neuronal gene expression subsequent to nerve injury: Etiological contribution to Complex Regional Pain Syndromes (Part II)

Kream

2014

Med Sci Monit

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Cumulating evidence indicated that nerve injury-associated cellular and molecular changes play an essential role in contributing to the development of pathological pain, and more recent findings implicated the critical role of epigenetic mechanisms in pain-related sensitization in the DRG subsequent to nerve injury. In this part of the dyad review (Part II), we reviewed and paid special attention on the etiological contribution of DGR gene expression modulated by epigenetic mechanisms of CRPS. As essential effectors to different molecular activation, we first discussed the activation of various signaling pathways that subsequently from nerve injury, and in further illustrated the fundamental and functional underpinnings of nerve injury-induced pain, in which we argued for the potential epigenetic mechanisms in response to sensitizing stimuli or injury. Therefore, understanding the specific mediating factors that influence individual epigenetic differences contributing to pain sensitivity and responsiveness to analgesics possesses crucial clinical implications.

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Clenbuterol upregulates histone demethylase JHDM2a via the β2-adrenoceptor/cAMP/PKA/p-CREB signaling pathway

Cited by 18 publications

References 50 publications

β2-Adrenergic receptor agonist ameliorates phenotypes and corrects microRNA-mediated IGF1 deficits in a mouse model of Rett syndrome

β2-Adrenergic receptor agonist ameliorates phenotypes and corrects microRNA-mediated IGF1 deficits in a mouse model of Rett syndrome

Single injection of clenbuterol into newly hatched chicks decreases abdominal fat pad weight in growing broiler chickens

Epigenetic modification of DRG neuronal gene expression subsequent to nerve injury: Etiological contribution to Complex Regional Pain Syndromes (Part II)

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