ATF3 in atherosclerosis: a controversial transcription factor

Wang, Bingyu; Yang, Xi; Sun, Xi; Liu, Jianhui; Fu, Yin; Liu, Bingyang; Qiu, Jun; Lian, Jing; Zhou, Jian

doi:10.1007/s00109-022-02263-7

Cited by 9 publications

(3 citation statements)

References 97 publications

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“…This indicated the pathological effect of ATF3 in diabetes [ 39 , 40 , 41 ]. There is a positive feedback loop between ATF3 and oxidative stress [ 42 , 43 ]. Moreover, ATF3 could promote erastin-induced ferroptosis by repressing SLC7A11 expression and suppressing system Xc [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

ATF3/SPI1/SLC31A1 Signaling Promotes Cuproptosis Induced by Advanced Glycosylation End Products in Diabetic Myocardial Injury

Huo

Wang

Shi

et al. 2023

IJMS

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Cuproptosis resulting from copper (Cu) overload has not yet been investigated in diabetic cardiomyopathy (DCM). Advanced glycosylation end products (AGEs) induced by persistent hyperglycemia play an essential role in cardiotoxicity. To clarify whether cuproptosis was involved in AGEs-induced cardiotoxicity, we analyzed the toxicity of AGEs and copper in AC16 cardiomyocytes and in STZ-induced or db/db-diabetic mouse models. The results showed that copper ionophore elesclomol induced cuproptosis in cardiomyocytes. It was only rescued by copper chelator tetrathiomolybdate rather than by other cell death inhibitors. Intriguingly, AGEs triggered cardiomyocyte death and aggravated it when incubated with CuCl2 or elesclomol–CuCl2. Moreover, AGEs increased intracellular copper accumulation and exhibited features of cuproptosis, including loss of Fe–S cluster proteins (FDX1, LIAS, NDUFS8 and ACO2) and decreased lipoylation of DLAT and DLST. These effects were accompanied by decreased mitochondrial oxidative respiration, including downregulated mitochondrial respiratory chain complex, decreased ATP production and suppressed mitochondrial complex I and III activity. Additionally, AGEs promoted the upregulation of copper importer SLC31A1. We predicted that ATF3 and/or SPI1 might be transcriptional factors of SLC31A1 by online databases and validated that by ATF3/SPI1 overexpression. In diabetic mice, copper and AGEs increases in the blood and heart were observed and accompanied by cardiac dysfunction. The protein and mRNA profile changes in diabetic hearts were consistent with cuproptosis. Our findings showed, for the first time, that excessive AGEs and copper in diabetes upregulated ATF3/SPI1/SLC31A1 signaling, thereby disturbing copper homeostasis and promoting cuproptosis. Collectively, the novel mechanism might be an alternative potential therapeutic target for DCM.

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Section: Discussionmentioning

confidence: 99%

ATF3/SPI1/SLC31A1 Signaling Promotes Cuproptosis Induced by Advanced Glycosylation End Products in Diabetic Myocardial Injury

Huo

Wang

Shi

et al. 2023

IJMS

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“…[53][54][55][56] As an important transcription factor, ATF3 interacts with a complex metabolic-immune response network in various cells, such as macrophages and ECs. 57 Several studies have suggested that the ATF3 function in metabolic, tumor, and cardiovascular diseases in part originates from its influence on cell metabolism. 1,[58][59][60] Abnormal metabolism induces stress reactions and subsequently influences ATF3-mediated inflammatory responses.…”

Section: Atf3 Mediates Inflammatory Responses By Interacting With a C...mentioning

confidence: 99%

“…31,32 Similarly, the expression of ATF3 in peripheral immune cells, such as macrophages, is involved in peripheral inflammation. 57 Thus, the underlying regulatory mechanism of ATF3 in inflammation is highly correlated with its participation in neuroinflammation.…”

Section: The Emerging Role Of Atf3 In Abi Associated Neuroinflammationmentioning

confidence: 99%

The multifaceted roles of activating transcription factor 3 (ATF3) in inflammatory responses – Potential target to regulate neuroinflammation in acute brain injury

Li,

Fan,

et al. 2023

J Cereb Blood Flow Metab

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Activating transcription factor 3 (ATF3) is one of the most important transcription factors that respond to and exert dual effects on inflammatory responses. Recently, the involvement of ATF3 in the neuroinflammatory response to acute brain injury (ABI) has been highlighted. It functions by regulating neuroimmune activation and the production of neuroinflammatory mediators. Notably, recent clinical evidence suggests that ATF3 may serve as a potential ideal biomarker of the long-term prognosis of ABI patients. This mini-review describes the essential inflammation modulatory roles of ATF3 in different disease contexts and summarizes the regulatory mechanisms of ATF3 in the ABI-induced neuroinflammation.

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The role of microglia heterogeneity in synaptic plasticity and brain disorders: Will sequencing shed light on the discovery of new therapeutic targets?

You,

Chen,

2024

Pharmacology & Therapeutics

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ATF3 in atherosclerosis: a controversial transcription factor

Cited by 9 publications

References 97 publications

ATF3/SPI1/SLC31A1 Signaling Promotes Cuproptosis Induced by Advanced Glycosylation End Products in Diabetic Myocardial Injury

ATF3/SPI1/SLC31A1 Signaling Promotes Cuproptosis Induced by Advanced Glycosylation End Products in Diabetic Myocardial Injury

The multifaceted roles of activating transcription factor 3 (ATF3) in inflammatory responses – Potential target to regulate neuroinflammation in acute brain injury

The role of microglia heterogeneity in synaptic plasticity and brain disorders: Will sequencing shed light on the discovery of new therapeutic targets?

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