Elevated plasma prostaglandins and acetylated histone in monocytes in Type 1 diabetes patients

Chen, S. S. H.; Jenkins, Alicia J.; Majewski, H.

doi:10.1111/j.1464-5491.2008.02658.x

Cited by 41 publications

(28 citation statements)

References 20 publications

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“…Results from related in vivo studies confirmed that the increased histone acetylation can lead to inflammatory gene transcription under diabetic conditions [40]. Moreover, data from a clinical trial suggested that elevated acetylated histone levels play an important role in both vascular injury and remodeling in Type 1 diabetes [41]. Similar to these collective findings, our study of the STZ-induced diabetes mouse model showed that the diabetic condition was associated with significant increases in total HAT activity and H3K9/14Ac level.…”

Section: Discussionmentioning

confidence: 98%

Novel curcumin analog C66 prevents diabetic nephropathy via JNK pathway with the involvement of p300/CBP-mediated histone acetylation

Wang

Luo

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Glomerulosclerosis and interstitial fibrosis represent the key events in development of diabetic nephropathy (DN), with connective tissue growth factor (CTGF), plasminogen activator inhibitor-1 (PAI-1) and fibronectin 1 (FN-1) playing important roles in these pathogenic processes. To investigate whether the plant metabolite curcumin, which exerts epigenetic modulatory properties when applied as a pharmacologic agent, may prevent DN via inhibition of the JNK pathway and epigenetic histone acetylation, diabetic and age-matched non-diabetic control mice were administered a 3-month course of curcumin analogue (C66), c-Jun N-terminal kinase inhibitor (JNKi, sp600125), or vehicle alone. At treatment end, half of the mice were sacrificed for analysis and the other half were maintained without treatment for an additional 3 months. Renal JNK phosphorylation was found to be significantly increased in the vehicle-treated diabetic mice, but not the C66- and JNKi-treated diabetic mice, at both the 3-month and 6-month time points. C66 and JNKi treatment also significantly prevented diabetes-induced renal fibrosis and dysfunction. Diabetes-related increases in histone acetylation, histone acetyl transferases’ (HATs) activity, and the p300/CBP HAT expression were also significantly attenuated by C66 or JNKi treatment. Chromatin immunoprecipitation assays showed that C66 and JNKi treatments decreased H3-lysine9/14-acetylation (H3K9/14Ac) level and p300/CBP occupancy at the CTGF, PAI-1 and FN-1 gene promoters. Thus, C66 may significantly and persistently prevent renal injury and dysfunction in diabetic mice via down-regulation of diabetes-related JNK activation and consequent suppression of the diabetes-related increases in HAT activity, p300/CBP expression, and histone acetylation.

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Section: Discussionmentioning

confidence: 98%

Novel curcumin analog C66 prevents diabetic nephropathy via JNK pathway with the involvement of p300/CBP-mediated histone acetylation

Wang

Luo

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…Acetylated histone H4 levels in the circulating monocytes were significantly elevated in complication-free diabetic patients, but not in patients with complications, suggesting that protein acetylation in the monocytes may be a protective mechanism. 28 …”

Section: Discussionmentioning

confidence: 99%

Inhibition of histone deacetylase 6 restores innate immune cells in the bone marrow in a lethal septic model

Zhao

Liu

et al. 2016

Journal of Trauma and Acute Care Surgery

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Background We have previously demonstrated that Tubastatin A, a selective inhibitor of histone deacetylase (HDAC) 6, improves survival, and increases circulating monocyte count and bacterial clearance in a lethal model of cecal ligation and puncture (CLP) in mice. The aim of the present study was to characterize the effects of inhibition of HDAC6 on the bone marrow cell population. Methods C57BL/6J mice were subjected to CLP, and 1 h later given an intraperitoneal injection of either Tubastatin A (70 mg/kg) dissolved in dimethyl sulfoxide (DMSO), or DMSO alone (n=9/group). Sham-operated animals were treated in an identical fashion, without CLP. Forty-eight hours later, bone marrow cells were flushed out from the femurs and tibias. Erythrocytes were lysed, and a single-cell suspension was made for analysis. Cells were washed, blocked with anti-mouse CD16/32, stained with anti-mouse B220 PE-Cy7, CD3 APC-eFluor® 780, CD11b FITC, Gr-1 PerCP-Cy5.5 and F4/80 Antigen APC, and subjected to flow cytometry. Data was acquired on an LSRII Flow Cytometer (BD Biosciences) and analyzed with FlowJo (Flowjo, LLC). Results In comparison to the sham group, CLP animals showed decreased percentage of innate immune cells (CD11b+; 62.1±3.1 vs. 32.9±4.9%, p=0.0025) and macrophages (CD11b+ F4/80+; 44.6±3.4 vs. 19.8±2.6%, p=0.0002), and increased percentage of T lymphocytes (CD3+; 1.1±0.2 vs. 3.3±0.4%, p=0.0082) in the bone marrow 48 h after CLP. Treatment with Tubastatin A restored the innate immune cells (32.9±4.9 vs. 54.0±4.1%, p=0.0112) and macrophages (19.8±2.6 vs. 47.1±4.6%, p=0.0001), and increased the percentage of neutrophils (CD11b+ Gr-1+; 28.4±3.9 vs. 48.0±4.0%, p=0.0075). The percentages of B (B220+) and T lymphocytes were not significantly altered by Tubastatin A, compared to the vehicle-treated CLP animals. Conclusions Selective inhibition of HDAC6 in this lethal septic model restored the innate immune cell and macrophage populations, and increased the neutrophil composition in the bone marrow. These results may explain the previously reported beneficial effects of Tubastatin A treatment in a septic model. Levels of Evidence not applicable (animal study).

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“…Elevated PGs have been observed in type 1 and type 2 diabetes (3,4). Epidemiological studies have indicated that the use of nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid (ASA), is associated with a significant reduction in the risk of diabetes in healthy populations (5).…”

mentioning

confidence: 99%

I Prostanoid Receptor–Mediated Inflammatory Pathway Promotes Hepatic Gluconeogenesis Through Activation of PKA and Inhibition of AKT

et al. 2014

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Nonsteroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid (ASA), improve glucose metabolism in diabetic subjects, although the underlying mechanisms remain unclear. In this study, we observed dysregulated expression of cyclooxygenase-2, prostacyclin biosynthesis, and the I prostanoid receptor (IP) in the liver's response to diabetic stresses. High doses of ASA reduced hepatic prostaglandin generation and suppressed hepatic gluconeogenesis in mice during fasting, and the hypoglycemic effect of ASA could be restored by IP agonist treatment. IP deficiency inhibited starvationinduced hepatic gluconeogenesis, thus inhibiting the progression of diabetes, whereas hepatic overexpression of IP increased gluconeogenesis. IP deletion depressed cAMP-dependent CREB phosphorylation and elevated AKT phosphorylation by suppressing PI3K-g/PKC-z-mediated TRB3 expression, which subsequently downregulated the gluconeogenic genes for glucose-6-phosphatase (G6Pase) and phosphoenol pyruvate carboxykinase 1 in hepatocytes. We therefore conclude that suppression of IP modulation of hepatic gluconeogenesis through the PKA/CREB and PI3K-g/PKC-z/TRB3/AKT pathways contributes to the effects of NSAIDs in diabetes.Glucose is the major source of energy required by most mammalian cells to maintain normal physiological functions. Glucose homeostasis is tightly regulated within a relatively narrow range by hormones such as glucagon and insulin and through balancing of glucose output by the liver and its utilization by peripheral tissues such as skeletal muscle, heart, and adipocytes. Liver is the dominant organ in the maintenance of glucose homeostasis, which is regulated by way of glucose production through glycogenolysis and gluconeogenesis, glucose uptake by glycogenesis, and glycolytic conversion to pyruvate (1). Circulating insulin increases in response to feeding, leading to glycogenesis and lipogenesis and the suppression of hepatic glucose production (HGP). Conversely, during fasting conditions or in the case of untreated type 1 diabetes, insulin secretion drops and glucagon secretion rises, prompting hepatic glycogenolysis and gluconeogenesis. The key regulatory enzymes for hepatic gluconeogenesis include glucose 6 phosphatase (G6Pase), fructose-1, 6-bisphosphatase, and phosphoenolpyruvate carboxykinase 1 (PEPCK), also known as PCK1. However, in patients with type 2 diabetes, the rate of hepatic gluconeogenesis is considerably elevated, contributing to fasting hyperglycemia and to exaggerated postprandial hyperglycemia.Prostaglandins (PGs) play important roles in inflammation-mediated diseases, including diabetes (2).

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Elevated plasma prostaglandins and acetylated histone in monocytes in Type 1 diabetes patients

Cited by 41 publications

References 20 publications

Novel curcumin analog C66 prevents diabetic nephropathy via JNK pathway with the involvement of p300/CBP-mediated histone acetylation

Novel curcumin analog C66 prevents diabetic nephropathy via JNK pathway with the involvement of p300/CBP-mediated histone acetylation

Inhibition of histone deacetylase 6 restores innate immune cells in the bone marrow in a lethal septic model

I Prostanoid Receptor–Mediated Inflammatory Pathway Promotes Hepatic Gluconeogenesis Through Activation of PKA and Inhibition of AKT

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