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Biomedical subjects

Y Z Zhu

Publications and source records attributed to Y Z Zhu.

At least 19 recordsLinked to original sources
PubMed2003

cDNA microarray analysis of gene expression in anxious PVG and SD rats after cat-freezing test.

To identify genes involved in the development of anxiety or fear, we analyzed the gene expression profiles of the cortex of anxious hooded PVG and Sprague-Dawley (SD) rats after exposure to the cat-freezing test apparatus. These two rat strains showed a marked difference in the extent of anxious behavior on the cat-freezing test; the hooded PVG rats showed highly anxious behavior while a low anxiety state was observed in SD rats. A cDNA microarray consisting of 5,931 genes was employed to investigate the global mRNA expression profiles of anxiety-related genes. According to the assumption that an abundance ratio of > or =1.5 is indicative of a change in gene expression, we detected 16 upregulated and 38 downregulated genes in PVG hooded and SD rats. Some of these genes have not yet been associated with anxiety (e.g. FGF), while other genes were recently found to be expressed in an anxious state (e.g., rat nerve growth factor-induced gene, NGFI-A). Our study also focused on the expression of some neurotransmitter receptors that have already been proven to be relevant to anxiety or fear, e.g., gamma-aminobutyric acid (GABA), cholecystokinin (CCK) and 5-HT(3) receptors. To further confirm the microarray data, the mRNA expressions of three genes: rat activity-regulated cytoskeleton-associated gene (Arc), rat NGFI-A gene and rat 5-HT(3) receptor (5-HT(3)R) mRNA, were studied by reverse transcription-polymerase chain reaction (RT-PCR). The results of RT-PCR were basically consistent with those from cDNA microarray. Our study therefore demonstrated that the microarray technique is an efficient tool for analyzing global expression profiles of anxiety-related genes, which may also provide further insight into the molecular mechanisms underlying the states of anxiety and fear.

Animals↗
PubMed2003

Genetic variations in CCK2 receptor in PVG hooded and Sprague-Dawley rats and its mRNA expression on cat exposure.

This study examined differential freezing behavior, mediated by cholecystokinin-2 (CCK2) receptors (J. M. Farook et al., 2001), in PVG hooded and Sprague-Dawley (SD) rats exposed to a predator. The authors confirmed by reverse transcription polymerase chain reaction that CCK2 receptor expression in the PVG rats was increased in the hippocampus and cerebral cortex compared with that of SD rats. In addition, 4 variations in the coding region of the CCK2 receptor gene were detected between the PVG hooded and SD rats: 1 in Exon 4, 1 in Intron 2, and 2 in Intron 3. Acute treatment with a CCK2 agonist (CCK-4) or antagonist (LY225910) did not alter the level of CCK2 receptor expression, indicating no difference between the 2 strains in sensitivity of the CCK2 receptor to drugs.

Animals↗
PubMed2001

Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila.

Proteins with expanded polyglutamine repeats cause Huntington's disease and other neurodegenerative diseases. Transcriptional dysregulation and loss of function of transcriptional co-activator proteins have been implicated in the pathogenesis of these diseases. Huntington's disease is caused by expansion of a repeated sequence of the amino acid glutamine in the abnormal protein huntingtin (Htt). Here we show that the polyglutamine-containing domain of Htt, Htt exon 1 protein (Httex1p), directly binds the acetyltransferase domains of two distinct proteins: CREB-binding protein (CBP) and p300/CBP-associated factor (P/CAF). In cell-free assays, Httex1p also inhibits the acetyltransferase activity of at least three enzymes: p300, P/CAF and CBP. Expression of Httex1p in cultured cells reduces the level of the acetylated histones H3 and H4, and this reduction can be reversed by administering inhibitors of histone deacetylase (HDAC). In vivo, HDAC inhibitors arrest ongoing progressive neuronal degeneration induced by polyglutamine repeat expansion, and they reduce lethality in two Drosophila models of polyglutamine disease. These findings raise the possibility that therapy with HDAC inhibitors may slow or prevent the progressive neurodegeneration seen in Huntington's disease and other polyglutamine-repeat diseases, even after the onset of symptoms.

Acetylation↗
PubMed2001

Strain differences in freezing behavior of PVG hooded and Sprague-Dawley rats: differential cortical expression of cholecystokinin2 receptors.

PVG hooded, but not Sprague-Dawley (SD), rats showed remarkable freezing behavior on cat exposure. Experiments using cDNA microarray and reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated that cholecystokinin (CCK)2 receptors were expressed to a greater extent in the PVG hooded rats. A CCK2 antagonist, LY225910, inhibited freezing behavior in the PVG hooded rats while a CCK2 agonist, CCK-4, increased freezing behavior in the SD rats. These results strongly suggest that CCK2 receptors mediate the freezing behavior and the differential expression of these receptors underlie the strain difference in such behavior.

Animals↗
PubMed2001

Time-dependent apoptotic development and pro-apoptotic genes expression in rat heart after myocardial infarction.

We investigated the apoptotic development and apoptotic-related gene expression after myocardial infarction (MI) at different time points in the current study. Bax gene expression was increased at 12 h after MI and peaked at 24 h. Fas gene started to over-express at 12 h after MI as well but it reached maximum at 72 h. In the MI groups, strongest staining of apoptosis was detected in rats 3 days post operation. Our results demonstrate that apoptotic development after MI is time dependent in the ischemic area and there could be some linkage with the over expression of angiotensin II receptors post MI.

Animals↗
PubMed2001

[Experimental study on effect of fuzheng yiliu decoction on tumor cell cycle and telomerease].

OBJECTIVE: To study the mechanism of anti-tumor effect of Fuzheng Yiliu Decoction (FZYLD). METHODS: S180 neoplasm strain was inoculated in Kunming mice to establish model of S180 solid tumor. The model animals were treated with FZYLD by gastrogavage, the cell cycle of tumor were checked up by flow cytometer and the telomerease kit was used to test telomerease activity. RESULTS: The stage G0/1 ratio of tumor cells in model animals treated with FZYLD increased, while cells of S stage decreased, with telomerease activity inhibited. These changes were different significantly from those in the model animals treated with normal saline (P < 0.001). CONCLUSION: FZYLD could block the tumor cell proliferation procedure and inhibit the DNA synthesis and duplication in tumor cell. And the suppression of telomerease activity might be one of the mechanisms affecting the tumor cell proliferation cycle.

Animals↗
PubMed2000

The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription.

Huntington's Disease (HD) is caused by an expansion of a polyglutamine tract within the huntingtin (htt) protein. Pathogenesis in HD appears to include the cytoplasmic cleavage of htt and release of an amino-terminal fragment capable of nuclear localization. We have investigated potential consequences to nuclear function of a pathogenic amino-terminal region of htt (httex1p) including aggregation, protein-protein interactions, and transcription. httex1p was found to coaggregate with p53 in inclusions generated in cell culture and to interact with p53 in vitro and in cell culture. Expanded httex1p represses transcription of the p53-regulated promoters, p21(WAF1/CIP1) and MDR-1. httex1p was also found to interact in vitro with CREB-binding protein (CBP) and mSin3a, and CBP to localize to neuronal intranuclear inclusions in a transgenic mouse model of HD. These results raise the possibility that expanded repeat htt causes aberrant transcriptional regulation through its interaction with cellular transcription factors which may result in neuronal dysfunction and cell death in HD.

Animals↗
PubMed2000

Expression of angiotensin II AT2 receptor in the acute phase of stroke in rats.

A male Wistar rat model of stroke (middle cerebral artery occlusion; MCAO) was used to study the angiotensin II (Ang II) receptor subtype 2 (AT2) gene expression by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining. After permanent occlusion of the middle cerebral artery (MCA), AT2 receptor gene expression was found to increase in the infarct cortex by 2.7-fold (1 day) and 1.7-fold (3 days), respectively. Positive AT2 immunostaining was also observed in the infarct area of the cerebral cortex. Apoptotic markers were detected in the necrotic area of the stroke cerebral cortex 1 day after MCAO. This demonstrated up-regulation of AT2 receptor may be involved in the apoptosis of tissue repair after stroke.

Acute Disease↗
PubMed2000

Expanded polyglutamine peptides alone are intrinsically cytotoxic and cause neurodegeneration in Drosophila.

Several dominant, late-onset neurodegenerative diseases (e.g. Huntington's disease) are caused by expansion of polyglutamine (polyQ) repeats within specific proteins. The diverse, yet overlapping, pathology of these diseases could be due to novel deleterious functions unique to each protein or to a common pathophysiology mediated by the long polyQ chains themselves. By engineering Drosophila to express different polyQ peptides, we find that expanded polyQ chains alone are intrinsically cytotoxic and cause neuronal degeneration and early adult death. We further find that this intrinsic toxicity is dependent on cell type and polyQ length and that the inclusion of other amino acids modifies and reduces toxicity. This is the first in vivo evidence that polyQs, when removed from their disease gene context, cause neurotoxicity. These studies provide a basis for understanding the diverse clinical presentations in terms of the intrinsic cytotoxic effect of polyQ peptides being modulated by protein context. Parallel experiments in which cytotoxic polyQ expansions were engineered into Dishevelled, a Drosophila protein containing a naturally occurring polyQ tract, strongly suggest that the effect of a toxic polyQ peptide can be neutralized by protein context. This animal model provides a simple and effective means of screening for therapeutics that relieves the polyQ-induced lethality, independent of any particular disease gene. By quantifying the degree of lethality in several transgenic lines, we have identified a number of genetically modified strains that are suitable for eventual testing of compounds or genes that ameliorate the pathology of polyQ peptides.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Identification of regulated genes in rat heart after myocardial infarction by means of differential mRNA display.

In order to testify the hypothesis that unknown mechanisms are involved in the process of cardiac remodeling after myocardial infarction (MI), we employed differential display reverse transcription-polymerase chain reaction (DDRT-PCR) as our primary inspection tool. An animal model of MI was established by ligation of the left anterior descending coronary artery (LAD) in rat. Fifty upregulated candidate cDNA fragments were obtained in the right ventricle (RV) of the heart six weeks after MI. Eight cDNA fragments isolated from DD denaturing gel were extracted and reamplified, cloned into pCR II vector and sequenced. A Genbank search of these clones showed that three of them have a high homology with known genes not previously associated with cardiac remodeling, i.e., mouse interleukin-4 receptor gene, rat ferritin mRNA, and T-cell receptor beta chain V beta 5. The remaining clones have no similarity to known sequences. These data suggest that certain genes which were not previously being associated with cardiac hypertrophy are turned on during the process of cardiac remodeling after MI.

Animals↗
PubMed2000

Effects of losartan on haemodynamic parameters and angiotensin receptor mRNA levels in rat heart after myocardial infarction.

We investigated the haemodynamic parameters and the regulation of cardiac mRNA levels of the angiotensin receptor subtypes, AT1 and AT2, by the AT,-receptor antagonist losartan in rat heart during the acute phase of myocardial infarction. AT1- andAT2-receptor mRNA levels markedly increased at 30 minutes and peaked at 24 hours post myocardial infarction (12.6-fold increase for AT1- and 17.2-fold increase for AT2 compared with controls). Losartan significantly reduced mean blood pressure in sham-operated rats and decreased mean blood pressure and left ventricular end-diastolic pressure in myocardial infarction rats. However, the AT,- andAT2-receptor mRNA levels of losartan-treated rats showed a pattern similar to that of water-treated rats. The time-dependent increase of AT1- and AT2-receptor mRNA levels is associated with the early remodelling process of non-infarcted myocardium post MI and is independent of AT1-receptor blockade.

Angiotensin Receptor Antagonists↗
PubMed2000

Salvia miltiorrhiza and ischemic diseases.

The demonstration of beneficial effects of salvia miltiorrhiza (DanShen) on ischemic diseases has revolutionized the management of angina pectoris, myocardial infarction (MI) or stroke in Chinese society. Experimental studies have shown that DanShen dilated coronary arteries, increased coronary blood flow, and scavenged free radicals in ischemic diseases, so that it reduced the cellular damage from ischemia and improved heart functions. Clinical trials also indicated that DanShen was an effective medicine for angina pectoris, MI, and stroke. This review will focus on DanShen's effects in angina pectoris, MI and stroke.

Angina Pectoris↗
PubMed2000

[Clinical study of effects of submaxillary transcutaneous electrical stimulation of genioglossus on obstructive sleep apnea syndrome].

OBJECTIVE: To investigate the effect of submaxillary transcutaneous electric stimulation of genioglossus on obstructive sleep apnea syndrome (OSAS). METHOD: Nineteen patients (male) with OSAS were diagnosed by polysomnography previously. Fixed the provocative locus of genioglossus and its controlling nerve with local anatomy. Estimated obstructive level of pharyngeal cavity by observing muller's maneuver under fiberolaryngoscope. Determined the effects of electric stimulation on different levels of narrow pharyngeal cavity with control study method. RESULT: The effect of electrical stimulation was different in different narrow level. The best effect was found on the obstruction of retrotongue-base-pharynx level, data of breath disorder (P < 0.05), oxygen saturation (P < 0.05) and clinical symptoms were significantly improved. The data were partly improved on multilevel obstructions of retrotongue-base-pharynx or above, no improvement was found on the obstruction of retrotongue-base-pharynx level. Dormant index was not worse. CONCLUSION: Submaxillary electrical stimulation is effective to the treatment of OSAS and its curative effect perhaps has a close relationship with obstructive level of with upper-airway. Further research on the mechanism showed that stimulating upper-airway dilating muscle which formed mainly by genioglossus could push the tongue ahead and effectively open pharyngeal cavity. Maybe it is a reason that the best effect took place on the retrotongue-base-pharynx level. Sleep was not affected by electrical stimulation.

Adult↗
PubMed1999

Effects of ramipril on cardiac gene transcription levels of angiotensin II receptors after myocardial infarction.

AIM: To study the early changes of cardiac angiotensin (Ang) II receptor gene transcription after myocardial infarction (MI) in rats chronically treated with the angiotensin-converting enzyme (ACE) inhibitor ramipril. METHODS: MI was induced by left anterior descending coronary artery ligation in rats and sham-operated rats were used as control. Rats were treated daily with ramipril (1 mg.kg-1) or water, initiated 1 wk before surgery. Quantitative RT-PCR was applied to determine the Ang II receptors AT1, AT2 receptor gene mRNA levels in the non-infarcted myocardium. RESULTS: AT1 and AT2 mRNA levels increased time point-dependently in the cardiac septum after MI reaching a peak on d 1. There was no significant difference of the myocardial AT1 and AT2 receptor mRNA levels between the ramipril-treated and water-treated rats after MI. CONCLUSION: The AT1 and AT2 receptor gene transcription in the non-infarcted myocardium was associated with the process of cardiac remodeling after MI but not affected by ACE inhibition.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Effect of transmembrane and kinase domain mutations on fibroblast growth factor receptor 3 chimera signaling in PC12 cells. A model for the control of receptor tyrosine kinase activation.

The effect of six point mutations causing various human skeletal dysplasias, occurring in the transmembrane (TM) and kinase domains (KD) of fibroblast growth factor receptor 3, were introduced into a chimera composed of the extracellular domain of human platelet-derived growth factor beta and the TM and intracellular domains of hFGFR3. Stable transfectants in rat PC12 cells showed distinct differences in the two classes of mutations. The cells containing TM mutants displayed normal expression and activation but higher responsiveness to lower doses of ligand. The KD mutants showed significantly altered expression patterns. Normal amounts of a lower Mr receptor (p130) reflecting incomplete glycosylation, but only greatly decreased amounts of the mature (p170) form, were observed. However, the latter material showed normal ligand-dependent activation. In contrast, the p130 form, which is regularly observed in the expression of both native and chimeric receptors, exhibits strong ligand-independent tyrosine phosphorylation, particularly with the K650E mutation. Expression of two of the KD mutants (K650M and K650E), under control of an inducible metallothionein promoter, indicated that this receptor was sufficiently autoactivated to produce at least partial differentiation and, in the case of the K650E mutation, to induce ligand-independent neurite outgrowth. A model is presented that suggests that the low Mr (p130) KD mutants can, under the right conditions, signal intracellularly, but when they are fully glycosylated and move to the cell surface they adopt a normal, inhibited conformation, in the form of ligand-independent dimers, that neutralizes the effects of the mutations. When ligands bind, these dimeric receptors are activated in a normal manner. This model suggests that unliganded dimers may be a common intermediate in receptor tyrosine kinase signaling.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Effects of angiotensin-converting enzyme inhibition and angiotensin II AT1 receptor antagonism on cardiac parameters in left ventricular hypertrophy.

Left ventricular hypertrophy (LVH) is considered to be an independent risk factor giving rise to ischemia, arrhythmia, and left ventricular dysfunction. In this article, we summarize recent studies performed in our laboratory to investigate (1) the contribution of the renin-angiotensin system to the cardiac remodeling process, which is triggered by myocardial infarction (MI) or hypertension-induced cardiac hypertrophy; (2) the effects of angiotensin-converting enzyme (ACE) inhibition and angiotensin AT1 receptor antagonism on cardiac parameters, such as myocardial infarct size, cardiac hypertrophy, heart function, and myocardial metabolism; (3) the mechanism of an ACE inhibitor-induced increase in cardiac capillary density in spontaneously hypertensive rats (SHR) and stroke prone SHR (SHR-SP). We observed that AT1 receptor gene expression in rat vascular smooth muscle cells (but not in rat coronary endothelial cells) was markedly enhanced after an ischemic insult in vitro. In a rat model in which MI was induced by coronary artery ligation, the AT1 receptor mRNA levels were transiently increased after MI and reached a peak level 24 hours post-MI. The AT2 receptor gene expression increased in a pattern similar to that of the AT1 receptor. ACE expression at the protein level in the repairing scar, which was demonstrated by monoclonal antibody staining, started to increase 2 weeks after MI and reached a peak level 3 weeks post-MI. Furthermore, long-term treatment with an ACE inhibitor limited infarct size, prevented cardiac hypertrophy, and improved heart function in the rat MI model. In SHR-SP, long-term treatment with either an ACE inhibitor or an AT1 receptor antagonist improved cardiac function and metabolism. Cardiac metabolism was even improved after low-dose ACE inhibitor treatment, which did not prevent hypertension and cardiac hypertrophy. In both SHR and SHR-SP, we found that the ACE inhibitor ramipril significantly increased capillary length density independently of its antihypertensive and antihypertrophic actions. Most of the cardiac effects of the ACE inhibitor could be abolished by a bradykinin B2 receptor antagonist. Thus, these cardiac effects of ACE inhibitors can be ascribed, at least under our experimental conditions, to ACE inhibitor-induced bradykinin potentiation.

Angiotensin Receptor Antagonists↗
PubMed1997

Antihypertensive and cardioprotective effects after angiotensin-converting enzyme inhibition: role of kinins.

Kinins are potent bioactive peptides formed by the enzymatic action of kallikrein on kininogens. The discovery that angiotensin-converting enzyme, which generates angiotensin II, is also a major degrading enzyme of kinins, gave rise to the hypothesis that kinin potentiation, in addition to angiotensin II reduction, may be involved in the therapeutic actions of angiotensin-converting enzyme inhibitors. Angiotensin-converting enzyme inhibitors have become important drugs in the treatment of hypertension, congestive heart failure, postmyocardial infarction, and diabetic nephropathy. Although angiotensin II reduction appears to be the predominant mechanism of the antihypertensive effect of chronic angiotensin-converting enzyme inhibitor treatment, the role of kinins in the antihypertensive effects of angiotensin-converting enzyme inhibitors seems to be renin dependent and cannot be generalized for all models of hypertension. On the other hand, at least under experimental conditions, various cardioprotective effects of angiotensin-converting enzyme inhibitors appear to be due to the potentiation of endogenous kinins, including improved cardiac function, structural changes following myocardial ischemia, and induction of capillary growth in hypertension-induced left ventricular hypertrophy.

Angiotensin-Converting Enzyme Inhibitors↗