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J-Y Wang

Publications and source records attributed to J-Y Wang.

24 records · Page 2Linked to original sources
PubMed2004

Genetic effect of two polymorphisms in the apolipoprotein A5 gene and apolipoprotein C3 gene on serum lipids and lipoproteins levels in a Chinese population.

Two polymorphisms, apolipoprotein A5 (APOA5) -1131T>C and apolipoprotein C3 (APOC3) -482C>T, were examined in a healthy Chinese group. Analysis of covariance (ancova) showed that both -1131T>C and -482C>T minor alleles were associated with triglyceride (TG)-raising effects (p < 0.001 and p = 0.012, respectively) after adjustment of sex, age, and body mass index (BMI). Moreover, -1131T>C minor alleles were also found to be associated with total cholesterol (TC)-raising effects (p = 0.045). However, the relationship between -482C>T minor alleles and TC-raising effects was not observed after adjustment of sex, age, and BMI. By contrast, significant inverse associations were noted between minor alleles (-1131T>C and -482C>T) and high-density lipoprotein cholesterol (HDL-C) concentrations (p = 0.021 and p = 0.021, respectively). Linear regression analysis showed that the effects of -1131T>C and -482C>T polymorphisms on TG and HDL-C (0.001 and 0.008; 0.041 and 0.005, respectively) are independent and additive and that -1131T>C can seriously affect the levels of TG (0.001 vs 0.008). The additive effect of the two polymorphisms was confirmed further by haplotype analysis. Our results strongly support that the two single nucleotide polymorphisms, -1131T>C in APOA5 and -482C>T in APOC3, are related to the levels of serum TG and HDL-C and those of other several lipids and lipoproteins in the Chinese population.

Apolipoprotein A-V↗
PubMed2003

Retinoblastoma protein (pRB) was significantly phosphorylated through a Ras-to-MAPK pathway in mutant K-ras stably transfected human adrenocortical cells.

Our previous studies have shown that the cell proliferation rate, mRNA levels of p450scc, p450c17, and 3betaHSD, and secretion of cortisol were significantly increased in human adrenocortical cells stably transfected with mutated K-ras expression plasmid "pK568MRSV" after being inducted with IPTG. In addition, the increased level was a time-dependent manner. However, the levels of p450, p450scc, p450c17, 3betaHSD, cortisol, and cell proliferation rate were inhibited by a MEK phospholation inhibitor, PD098059. The above results prove that mutated K-ras oncogene is able to regulate tumorigenesis and steroidogenesis through a Ras-RAF-MEK-MAPK signal transduction pathway. The aim of this study was to investigate regulated factors in this pathway and also examine whether the other signal transduction pathways or other moles involved in tumorigenesis or steroidogenesis. In the first year, we analyzed gene profiles of mutant K-ras-transfected adrenocortical cells by DNA microarray to determine the gene expression related to cell cycle, signal transduction, apoptosis, tumorigenesis, steroidogenesis, and other expressed sequence tag. After being affected by the K-ras mutant, gene expression was significantly increased in some upregulated genes. Human zinc-finger protein 22 increased by 28.5 times, Osteopontin increased by 5.8 times, LIM domain Kinase 2 (LIMK2) increased by 3.3 times, Homo sapiens dual-specificity tyrosine-(Y)-phosphorylation regulated Kinase 2 (DYRK2) increased by 2.2 times, and human syntaxin 3 increased by two times. On the other hand, significant decreases in gene expression were also observed in some downregulated genes. Retinoblastoma binding protein 1 (RBBP1) decreased by four times, Homo sapiens craniofacial development protein 1 (CFDP1) decreased by 2.4 times, DAP Kinase-related apoptosis-inducing protein Kinase 1 (DRAK1) decreased by 2.3 times, SKI-interacting protein (SKIP) decreased by 2.2 times, and human poly(A)-Binding protein (PABP) decreased by 2.1 times. In all significant differentially expressed genes, preliminary analysis by bioinformatics revealed that after induced K-ras mutant expression by isopropyl thiogalctoside (IPTG), the downregulation of RBBP1 gene was most correlated to cell proliferation. RBBP1 can bind with RB/E2F to form a mSIN3-HDAC complex, which induces cell cycle arrest in the G1/G0 stage by repressing transcription of E2F-regulated genes. The result of a Northern blot showed that RBBP1 were inhibited after an induction of IPTG for 36 h. Another Northern blot analysis proved that mRNA levels of cyclin D1 and c-myc increased in proportion to K-ras expression. Finally, Western blot was carried out, and the results showed that phosphorylated pRB also increased. Taken together, we infer that the mutant K-ras oncogene promoted the cells to proceed to the G1/S stage by the inhibiting the formation of RB/RBBP1-dependent repressor complex from binding with the SIN3-HDAC complex, which resulted in the acetylation of histone to active transcription of E2F-regulated genes. However, the roles of the other differentially expressed genes involved in cell proliferation, cell morphologic change, tumorigenesis, or steroidogenesis still need further investigation.

Adrenal Cortex↗
PubMed2003

Vasoactive mediators and renal haemodynamics in exertional heat stroke complicated by acute renal failure.

BACKGROUND: Although vasoactive substances may be important in the pathogenesis of some types of acute renal failure (ARF), their potential role in exertional heat stroke (ExHS) with ARF has not been explored. AIM: To evaluate whether changes in concentration of individual vasoactive mediators correlated with alterations in renal function and haemodynamics in patients with ExHS and ARF. DESIGN: Prospective case-control study. METHODS: Systemic and renal haemodynamics, circulating vasoactive hormones and urinary vasodilator metabolites were determined in 12 military recruits who developed ExHS with ARF but without other organ failure during a three-year period. The control group consisted of 12 recruits who performed similar exercise under the same conditions without developing ExHS. RESULTS: There were significant elevations in circulating pressor hormones (catecholamines, renin, aldosterone and endothelin-1 (ET-1)) and significant decreases in the vasodilatory hormone prostaglandin E(2) (PGE(2)) in the acute phase of ExHS with ARF when compared to ExC. There was also a significant rise in nitric oxide metabolites (NOx) in the acute phase of ExHS. All of these abnormalities in circulating hormones returned to normal range during the recovery phase of ExHS. The ERPF correlated positively with GFR and urinary PGE(2) and negatively with plasma catecholamines, renin, ET-1 and NOx. DISCUSSION: The changes in the plasma levels of these hormones, together with enhanced NO production, may both contribute to the pathophysiology of ARF in ExHS.

Acute Kidney Injury↗
PubMed2002

Mutant K-ras oncogene regulates steroidogenesis of normal human adrenocortical cells by the RAF-MEK-MAPK pathway.

The result of our previous study has shown that the K-ras mutant (pK568MRSV) transfected human adrenocortical cells can significantly increase cortisol production and independently cause cell transformation. The aim of this study is to investigate the effect of the active K-ras oncogene on the cortisol production in normal human adrenocortical cells. First we used isopropyl thiogalactoside to induce the inducible mutant K-ras expression plasmid, pK568MRSV, in the stable transfected human adrenocortical cells. The result showed that the increase of RasGTP levels in transfected cells was time-dependent after isopropyl thiogalactoside induction. Additionally, results from Western blot analysis revealed significant elevation in phosphorylation of c-Raf-1 and Mitogen-activated protein kinase. We also detected the levels of mRNA encoding Cholesterol side-chain cleavage enzyme (P450(SCC)), 17alpha-Hydroxylase/17,20-lyase (P450(c17)) and 3beta-Hydroxysteroid dehydrogenase (3betaHSD) were increased in human adrenocortical cells transfected with mutant K-ras after IPTG treatment. The increase of mRNA amount in P450(scc) P450(c17) and 3betaHSD and the elevation of cortisol level were inhibited with a pretreatment of PD098059, a specific extracellular signal-regulated kinase inhibitor. In our previous report, we proved that lovastatin, a pharmacological inhibitor of p21(ras) function, also reversed the increase of cortisol level in mutant K-ras stably transfected human adrenocortical cells. Taken together, these findings proved that the active mutant Ras enhanced not only cell proliferation but also steroidogenesis in steroidogenic phenotype cells by activating Raf-MEK-MAPK related signal transduction pathway. Therefore, we believe that K-ras mutants influence regulation of steroidogenesis in adrenocortical cells through RAF-MEK-MAPK pathway.

Adrenal Cortex↗
PubMed2002

Granulocytes mediates the Fas-L-associated apoptosis during lung metastasis of melanoma that determines the metastatic behaviour.

The survival of tumour cells in a new tissue environment is crucial for tumour metastasis. Factors contributing to the death of tumour cells during metastasis are not completely understood. In murine melanoma model, activation of Fas (CD95, APO-1) signal in tumour cells reduces their lung metastasis potential, which may be associated with an induction of apoptosis in tumours. To elucidate the cellular mechanism, we used a Fas-ligand (Fas-L) specific ribozyme (Fas-L(ribozyme)) to suppress the expression of Fas-L but not Fas or TNF-alpha in B16F10 melanoma cells. The Fas-L(ribozyme)-carrying cells grew slightly faster in vitro with better viability than controls. Suppression of Fas-L in B16F10 melanoma cells by Fas-L(ribozyme) enhanced lung metastasis of the cells in C57BL/6 mice, and that was correlated with reductions in both apoptotic tumour cells and granulocytic infiltration. Mice depleted of granulocytes, but not CD4+ and CD8+ cells, showed a greatly elevated susceptibility to lung metastasis. Moreover, apoptosis in tumour cells was significantly reduced in granulocyte-depleted mice during the course of tumour formation. Taken together, our findings indicate that Fas-L-associated apoptosis in tumour cells determines the metastasis behaviour of melanoma in the lung and this apoptosis is primarily mediated by the cytotoxicity of recruited granulocytes.

Apoptosis↗