Abstract：
:Increased expression of DNA methyltransferase-1 (DNMT1) associates with the progression of many human diseases. Because DNMT1 induces cell proliferation, drugs that inhibit DNMT1 have been used to treat proliferative diseases. Because these drugs are nonspecific inhibitors of DNMT1, subsidiary events or the compensatory mechanisms that are activated in the absence of DNMT1 limit their therapeutic application. Here, we studied the molecular mechanisms that occur during angioplasty-induced restenosis and found that DNMT1 inhibition in both in vitro and in vivo approaches resulted in the induction of DNA methyltransferase-3a (DNMT3a) expression. In vascular smooth muscle cells (VSMCs), the microRNA hsa-miR-1264 mimic, specifically inhibiting DNMT1, induced nuclear expression of DNMT3a. On the contrary, there was no induced expression of DNMT3a in VSMCs that were transfected with hsa-miR-1264 inhibitor. Further, ectopic expression of suppressor of cytokine signaling 3 (SOCS3) through adeno-associated virus (AAV)-mediated gene delivery in the coronary arteries of Yucatan microswine showed inhibition of both DNMT1 and DNMT3a in vivo. These findings show the existence of an inter-regulatory mechanism between DNMT1 and DNMT3a where, in the absence of DNMT1, induction of DNMT3a compensates for the loss of DNMT1 functions, suggesting that the inhibition of both DNMT1 and DNMT3a are required to prevent restenosis.
journal_name
Can J Physiol Pharmacoljournal_title
Canadian journal of physiology and pharmacologyauthors
Boosani CS,Gunasekar P,Block M,Jiang W,Zhang Z,Radwan MM,Agrawal DKdoi
10.1139/cjpp-2018-0111subject
Has Abstractpub_date
2018-10-01 00:00:00pages
1030-1039issue
10eissn
0008-4212issn
1205-7541journal_volume
96pub_type
杂志文章abstract：:The purpose of this study was to explore the protective effect of BW373U86 (a δ-opioid receptor (DOR) agonist) on ischemia-reperfusion (I/R) injury in rat cardiomyocytes and its underlying mechanism. Primary rat cardiomyocytes were cultured and pretreated with BW373U86 for intervention. The cardiomyocytes were culture...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2019-0684
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abstract：:This review presents, from the author's viewpoint, avenues of histamine research likely to produce new information. One potentially useful approach may be to attempt to relate histamine's function to its occurrence in different body tissues such as the pituitary and hypothalamus, the gastrointestinal mucosa, and the b...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：
更新日期：1985-06-01 00:00:00
abstract：:Although mitochondrial transcription factor A (TFAM) is a protective component of mitochondrial DNA and a regulator of calcium and reactive oxygen species (ROS) production, the mechanism remains unclear. In heart failure, TFAM is significantly decreased and cardiomyocyte instability ensues. TFAM inhibits nuclear facto...
journal_title：Canadian journal of physiology and pharmacology
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doi：10.1139/cjpp-2016-0718
更新日期：2018-02-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
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journal_title：Canadian journal of physiology and pharmacology
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doi：
更新日期：2001-08-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2018-0266
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y81-080
更新日期：1981-06-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y87-327
更新日期：1987-10-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y93-003
更新日期：1993-01-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y85-083
更新日期：1985-05-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y91-173
更新日期：1991-08-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：
更新日期：1999-11-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：10.1139/y06-077
更新日期：2006-12-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2019-0679
更新日期：2020-09-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2019-0686
更新日期：2020-09-01 00:00:00
abstract：:Endometritis is one of the main diseases that harms the dairy cow industry. Tanshinone IIA (TIIA), a fat-soluble alkaloid isolated from Salviae miltiorrhizae, has been reported to have potent anti-inflammatory properties. However, the anti-inflammatory effects of TIIA on a mouse model of lipopolysaccharide (LPS)-induc...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2015-0003
更新日期：2015-11-01 00:00:00
abstract：:The our objective was to investigate the adaptations induced by a low-protein, high-carbohydrate (LPHC) diet in growing rats, which by comparison with the rats fed a control (C) diet at displayed lower fasting glycemia and similar fasting insulinemia, despite impairment in insulin signaling in adipose tissues. In the ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2013-0346
更新日期：2014-06-01 00:00:00
abstract：:Ten minutes after KCl-depolarization of rat myometrial strips, at which time the muscles were in a state of sustained contracture, tissue levels of adenosine 3',5'-cyclic monophosphate (cyclic AMP) were increased by approximately 40% over relaxed controls, and levels of guanosine 3',5'-cyclic monophosphate (cyclic GMP...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y75-153
更新日期：1975-12-01 00:00:00
abstract：:The world-wide increase in cancer incidence imposes a corresponding significant increase in the use of chemotherapeutic agents. Nephrotoxicity is a side effect frequently encountered with cyclophosphamide (CP), which is also well-known to cause acute and chronic lung toxicities. The current study focuses on the evalua...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2015-0070
更新日期：2016-04-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y89-041
更新日期：1989-03-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y86-237
更新日期：1986-11-01 00:00:00
abstract：:In this study, we examined the effect of hydrogen peroxide on the accumulation of various mRNAs encoding heat shock proteins (hsps) and proto-oncogenes in Xenopus A6 kidney epithelial cells. Hydrogen peroxide treatment enhanced the accumulation of hsp90, hsp70, hsp30, c-jun, c-fos, and actin mRNAs with distinct tempor...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y04-059
更新日期：2004-07-01 00:00:00
abstract：:The aim of this study was to determine if there was a synergistic or additive effect of a thiazolidinedione derivative (rosiglitazone (ROS)) and a vanadium compound (bis(ethylmaltolato)oxovanadium(IV) (BEOV)) on plasma glucose and insulin levels following chronic oral administration to Zucker diabetic fatty (ZDF) rats...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y03-094
更新日期：2003-11-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y80-030
更新日期：1980-02-01 00:00:00
abstract：:The activity of the lipolytic system of the obese hyperglycemic mouse was assessed after treatment with physiological doses of thyroxin (T4). The treatment significantly increased fatty acid mobilization in response to adrenaline over the levels observed in the control mice under all conditions studied. The activities...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y77-177
更新日期：1977-12-01 00:00:00
abstract：:The neural connections from the medial prefrontal cortex to the ventral pallidum were investigated in urethane-anesthetized rats. Extracellular recordings were made from 124 spontaneously firing neurons in the ventral pallidum while the medial prefrontal cortex was electrically stimulated. The most frequent response t...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y93-053
更新日期：1993-05-01 00:00:00
abstract：:The direct effects of extrinsic nerve stimulation on coronary artery tone are unclear because of the complications arising from alterations in myocardial dynamics which themselves alter flow. An isolated and perfused nonbeating slab of beef ventricle was utilized in the present experiments to eliminate secondary compl...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y79-043
更新日期：1979-03-01 00:00:00
abstract：:A study of the relationship between the mechanical response of human iliac arteries subjected to sinusoidally varying dynamic pressures superimposed on a static pressure of 100 mm Hg (1mm Hg = 133 N/m2) and the development of arterial dilatation, with particular reference to poststenotic dilatation has been conducted....
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y75-138
更新日期：1975-12-01 00:00:00
abstract：:Sensorimotor mechanisms were studied on the basis of kinematic and electromyographic data as well as the static torque developed by the muscles as a function of joint angle. The latter relationship is known as the torque/angle characteristic. Fast single-joint movement may result from a shift in this characteristic an...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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更新日期：1995-02-01 00:00:00
abstract：:Pioglitazone (Pio) and swimming exercise (SE) are insulin sensitisers. This investigation was suggested because of the significant side effects associated with Pio treatment in metabolic syndrome (MetS). This study was, therefore, designed to investigate the preventive role of Pio treatment and SE in terms of efficien...
journal_title：Canadian journal of physiology and pharmacology
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更新日期：2014-02-01 00:00:00
