GPR39 promotes cardiac hypertrophy by regulating the AMPK–mTOR pathway and protein synthesis

Liao, Haojie; Gao, Weinian; Ma, Jie; Xue, Hongyuan; Wang, Yi; Huang, Dai; Yan, Fang; Ye, Yuquan

doi:10.1002/cbin.11566

Cited by 11 publications

(8 citation statements)

References 38 publications

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“…Recent studies have suggested that ribosome biogenesis plays an important role in cardiac hypertrophy by promoting or inhibiting the pathological process. 149 , 150 …”

Section: Ribosomes and Cardiovascular Diseases (Cvds)mentioning

confidence: 99%

“…Recent studies have suggested that ribosome biogenesis plays an important role in cardiac hypertrophy by promoting or inhibiting the pathological process. 149,150 The rDNA transcription rate is positively correlated with the degree of phosphorylation of RNA Pol I and the upstream binding factor (UBF). Studies have shown that the hypophosphorylated form of UBF blocks rDNA transcription by disrupting the UBF/SL1 complex.…”

Section: Ribosome and Cardiac Hypertrophymentioning

confidence: 99%

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Ribosome biogenesis in disease: new players and therapeutic targets

Jiao

Liu

et al. 2023

Sig Transduct Target Ther

101

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The ribosome is a multi-unit complex that translates mRNA into protein. Ribosome biogenesis is the process that generates ribosomes and plays an essential role in cell proliferation, differentiation, apoptosis, development, and transformation. The mTORC1, Myc, and noncoding RNA signaling pathways are the primary mediators that work jointly with RNA polymerases and ribosome proteins to control ribosome biogenesis and protein synthesis. Activation of mTORC1 is required for normal fetal growth and development and tissue regeneration after birth. Myc is implicated in cancer development by enhancing RNA Pol II activity, leading to uncontrolled cancer cell growth. The deregulation of noncoding RNAs such as microRNAs, long noncoding RNAs, and circular RNAs is involved in developing blood, neurodegenerative diseases, and atherosclerosis. We review the similarities and differences between eukaryotic and bacterial ribosomes and the molecular mechanism of ribosome-targeting antibiotics and bacterial resistance. We also review the most recent findings of ribosome dysfunction in COVID-19 and other conditions and discuss the consequences of ribosome frameshifting, ribosome-stalling, and ribosome-collision. We summarize the role of ribosome biogenesis in the development of various diseases. Furthermore, we review the current clinical trials, prospective vaccines for COVID-19, and therapies targeting ribosome biogenesis in cancer, cardiovascular disease, aging, and neurodegenerative disease.

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“…Recent studies have suggested that ribosome biogenesis plays an important role in cardiac hypertrophy by promoting or inhibiting the pathological process. 149 , 150 …”

Section: Ribosomes and Cardiovascular Diseases (Cvds)mentioning

confidence: 99%

Section: Ribosome and Cardiac Hypertrophymentioning

confidence: 99%

Ribosome biogenesis in disease: new players and therapeutic targets

Jiao

Liu

et al. 2023

Sig Transduct Target Ther

101

View full text Add to dashboard Cite

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“…Furthermore, a screen of repurposed drugs found gandotinib as a potential contraceptive [ 74 ]. On the other hand, antagonism was recently suggested as beneficial in the treatment of myocardial infarction [ 14 ] or cardiac hypertrophy [ 15 ]. Enhanced expression of GPR39 has been documented in the aging human brain [ 17 ] and cancers [ 75 ].…”

Section: Discussionmentioning

confidence: 99%

TC-G 1008 facilitates epileptogenesis by acting selectively at the GPR39 receptor but non-selectively activates CREB in the hippocampus of pentylenetetrazole-kindled mice

Doboszewska

Socała

Pieróg

et al. 2023

Cell. Mol. Life Sci.

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The pharmacological activation of the GPR39 receptor has been proposed as a novel strategy for treating seizures; however, this hypothesis has not been verified experimentally. TC-G 1008 is a small molecule agonist increasingly used to study GPR39 receptor function but has not been validated using gene knockout. Our aim was to assess whether TC-G 1008 produces anti-seizure/anti-epileptogenic effects in vivo and whether the effects are mediated by GPR39. To obtain this goal we utilized various animal models of seizures/epileptogenesis and GPR39 knockout mice model. Generally, TC-G 1008 exacerbated behavioral seizures. Furthermore, it increased the mean duration of local field potential recordings in response to pentylenetetrazole (PTZ) in zebrafish larvae. It facilitated the development of epileptogenesis in the PTZ-induced kindling model of epilepsy in mice. We demonstrated that TC-G 1008 aggravated PTZ-epileptogenesis by selectively acting at GPR39. However, a concomitant analysis of the downstream effects on the cyclic-AMP-response element binding protein in the hippocampus of GPR39 knockout mice suggested that the molecule also acts via other targets. Our data argue against GPR39 activation being a viable therapeutic strategy for treating epilepsy and suggest investigating whether TC-G 1008 is a selective agonist of the GPR39 receptor.

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“…Liao et al demonstrated that GPR39 inhibited AMPK signaling with mTOR and S6k1 activation, which induced the activation of de novo protein synthesis, leading to cardiac hypertrophy in mice. GPR39 overexpression in neonatal cardiomyocytes exacerbates angiotensin II-induced cardiac hypertrophy [ 65 ].…”

Section: Membrane Proteins Regulating Zinc Homeostasis In Calcium Hom...mentioning

confidence: 99%

Zinc in Cardiovascular Functions and Diseases: Epidemiology and Molecular Mechanisms for Therapeutic Development

Hara

Yoshigai

Ohashi

et al. 2023

IJMS

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Zinc is an essential trace element that plays an important physiological role in numerous cellular processes. Zinc deficiency can result in diverse symptoms, such as impairment of the immune response, skin disorders, and impairments in cardiovascular functions. Recent reports have demonstrated that zinc acts as a signaling molecule, and its signaling pathways, referred to as zinc signals, are related to the molecular mechanisms of cardiovascular functions. Therefore, comprehensive understanding of the significance of zinc-mediated signaling pathways is vital as a function of zinc as a nutritional component and of its molecular mechanisms and targets. Several basic and clinical studies have reported the relationship between zinc level and the onset and pathology of cardiovascular diseases, which has attracted much attention in recent years. In this review, we summarize the recent findings regarding the effects of zinc on cardiovascular function. We also discuss the importance of maintaining zinc homeostasis in the cardiovascular system and its therapeutic potential as a novel drug target.

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GPR39 promotes cardiac hypertrophy by regulating the AMPK–mTOR pathway and protein synthesis

Cited by 11 publications

References 38 publications

Ribosome biogenesis in disease: new players and therapeutic targets

Ribosome biogenesis in disease: new players and therapeutic targets

TC-G 1008 facilitates epileptogenesis by acting selectively at the GPR39 receptor but non-selectively activates CREB in the hippocampus of pentylenetetrazole-kindled mice

Zinc in Cardiovascular Functions and Diseases: Epidemiology and Molecular Mechanisms for Therapeutic Development

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