The Involvement of NFAT Transcriptional Activity Suppression in SIRT1-Mediated Inhibition of COX-2 Expression Induced by PMA/Ionomycin

Jia, Yong; Lu, Jie; Huang, Yue; Liu, Guang; Gao, Peng; Wan, Yong; Zhang, Ran; Zhang, Zhu-Qin; Yang, Ruifeng; Tang, Xiaoqiang; Xu, Jing; Wang, Xu; Chen, Hou-Zao; Liu, De-Pei

doi:10.1371/journal.pone.0097999

Cited by 27 publications

(20 citation statements)

References 41 publications

(52 reference statements)

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“…Abbreviation: VEGF, vascular endothelial cell growth factor. and VSMCs in CVDs [150][151][152]. As thus, β-hydroxybutyrate-mediated protection of vascular cell senescence may be partially mediated by p53 β-hydroxybutyrylation.…”

Section: Figure 7 Succinate In Cvdsmentioning

confidence: 92%

Short-chain fatty acid, acylation and cardiovascular diseases

2020

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Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Metabolic dysfunction is a fundamental core mechanism underlying CVDs. Previous studies generally focused on the roles of long-chain fatty acids (LCFAs) in CVDs. However, a growing body of study has implied that short-chain fatty acids (SCFAs: namely propionate, malonate, butyrate, 2-hydroxyisobutyrate (2-HIBA), β-hydroxybutyrate, crotonate, succinate, and glutarate) and their cognate acylations (propionylation, malonylation, butyrylation, 2-hydroxyisobutyrylation, β-hydroxybutyrylation, crotonylation, succinylation, and glutarylation) participate in CVDs. Here, we attempt to provide an overview landscape of the metabolic pattern of SCFAs in CVDs. Especially, we would focus on the SCFAs and newly identified acylations and their roles in CVDs, including atherosclerosis, hypertension, and heart failure. Clinical Science (2020) 134 657-676 https://doi.org/10.1042/CS20200128 cofactors in certain protein acylations, such as propionylation [14], malonylation [15], butyrylation [14], 2-hydroxyisobutyrylation [16], β-hydroxybutyrylation [17], crotonylation [18], succinylation [19], and glutarylation [20]. These discoveries give us a deeper understanding of PTM. Among PTMs, protein acetylation is the earliest discovered and most studied. Similar to protein acetylation, various studies have shown that these newly discovered PTMs are also involved in physiological and pathophysiological processes, including cardiovascular homeostasis.Here in this review, we will summarize SCFAs, protein acylations, and their emerging roles in CVDs, including atherosclerosis, hypertension, and heart failure. The metabolic pattern and FAs in CVDsThe heart is an 'omnivore' , using FAs, glucose, lactate, ketone bodies, and amino acids as metabolic substrates [5,6]. The substrates utilized by the embryonic heart are significantly different from those used by the adult heart. The embryonic heart depends primarily on glycolysis as well as lactate oxidation to produce energy [21]. The newborn and adult heart shift toward the remarkable utilization of FAs to meet cardiac energy demand [5,9]. In failing hearts, a decrease in FA oxidation and an increase in glycolysis are critically involved in cardiac dysfunction [22]. As thus, the metabolic pattern is essential for maintaining cardiac and vascular functions.Diabetes, hypertension, and obesity contribute to heart failure syndrome. Accumulating evidence suggests that hypertension, ischemic hearts, and heart failure induce a shift in substrate toward the remarkable utilization of glucose to generate energy. Despite this shift, the FA oxidation remains to make much energy for the diseased heart [23]. Since FAs are the predominant substrates for cardiomyocytes, alterations in FA metabolism have been implicated as causal in cardiac diseases. FAs within cells and in the circulation are critically involved in cardiometabolic diseases. CVDs are closely associated with lifestyle and metabolic status, which affect circul...

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Section: Figure 7 Succinate In Cvdsmentioning

confidence: 92%

Short-chain fatty acid, acylation and cardiovascular diseases

2020

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“…SIRT1 is a NAD + dependent histone/protein deacetylase which has been implicated in a wide array of cellular events including starvation, inflammation, oxidative stress and senescence [21]. SIRT1 mediates these cellular events in part through directly deacetylating several transcription factors such as p53 [22], FOXOs [23], Egr-1 [24], p65 [25], and NFATc3 [26]. Among these transcription factors, Rel family members p65 and NFATc3 were identified to be negatively regulated by direct SIRT1 dependent deacetylation [25,26].…”

Section: Introductionmentioning

confidence: 99%

“…SIRT1 mediates these cellular events in part through directly deacetylating several transcription factors such as p53 [22], FOXOs [23], Egr-1 [24], p65 [25], and NFATc3 [26]. Among these transcription factors, Rel family members p65 and NFATc3 were identified to be negatively regulated by direct SIRT1 dependent deacetylation [25,26]. Yet, presence of such mechanism and its consequence in another Rel family member, NFAT5, remain unsettled.…”

Section: Introductionmentioning

confidence: 99%

SIRT1 contributes to aldose reductase expression through modulating NFAT5 under osmotic stress: In vitro and in silico insights

Timuçin

Bodur

Başağa

2015

Cellular Signalling

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“…Sirt1 activates PGC-1a and negatively regulates NFAT, mTOR, and HIF-1a activity (149, 153, 154). This effect could reduce metabolic cell stresses and improve the effectiveness of PD-1 blockade therapy.…”

Section: Targeting Cell Regulatory Pathways and Immune Checkpoints Asmentioning

confidence: 99%

Adjunct Strategies for Tuberculosis Vaccines: Modulating Key Immune Cell Regulatory Mechanisms to Potentiate Vaccination

Jayashankar

Hafner

2016

Front. Immunol.

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Tuberculosis (TB) remains a global health threat of alarming proportions, resulting in 1.5 million deaths worldwide. The only available licensed vaccine, Bacillus Calmette–Guérin, does not confer lifelong protection against active TB. To date, development of an effective vaccine against TB has proven to be elusive, and devising newer approaches for improved vaccination outcomes is an essential goal. Insights gained over the last several years have revealed multiple mechanisms of immune manipulation by Mycobacterium tuberculosis (Mtb) in infected macrophages and dendritic cells that support disease progression and block development of protective immunity. This review provides an assessment of the known immunoregulatory mechanisms altered by Mtb, and how new interventions may reverse these effects. Examples include blocking of inhibitory immune cell coreceptor checkpoints (e.g., programed death-1). Conversely, immune mechanisms that strengthen immune cell effector functions may be enhanced by interventions, including stimulatory immune cell coreceptors (e.g., OX40). Modification of the activity of key cell “immunometabolism” signaling pathway molecules, including mechanistic target of rapamycin, glycogen synthase kinase-3β, wnt/β-catenin, adenosine monophosophate-activated protein kinase, and sirtuins, related epigenetic changes, and preventing induction of immune regulatory cells (e.g., regulatory T cells, myeloid-derived suppressor cells) are powerful new approaches to improve vaccine responses. Interventions to favorably modulate these components have been studied primarily in oncology to induce efficient antitumor immune responses, often by potentiation of cancer vaccines. These agents include antibodies and a rapidly increasing number of small molecule drug classes that have contributed to the dramatic immune-based advances in treatment of cancer and other diseases. Because immune responses to malignancies and to Mtb share many similar mechanisms, studies to improve TB vaccine responses using interventions based on “immuno-oncology” are needed to guide possible repurposing. Understanding the regulation of immune cell functions appropriated by Mtb to promote the imbalance between protective and pathogenic immune responses may guide the development of innovative drug-based adjunct approaches to substantially enhance the clinical efficacy of TB vaccines.

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The Involvement of NFAT Transcriptional Activity Suppression in SIRT1-Mediated Inhibition of COX-2 Expression Induced by PMA/Ionomycin

Cited by 27 publications

References 41 publications

Short-chain fatty acid, acylation and cardiovascular diseases

Short-chain fatty acid, acylation and cardiovascular diseases

SIRT1 contributes to aldose reductase expression through modulating NFAT5 under osmotic stress: In vitro and in silico insights

Adjunct Strategies for Tuberculosis Vaccines: Modulating Key Immune Cell Regulatory Mechanisms to Potentiate Vaccination

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