Biomedical subjects

Yi-Tang Tseng

Publications and source records attributed to Yi-Tang Tseng.

4 recordsLinked to original sources

PubMed2005

Ontogeny of phosphoinositide 3-kinase signaling in developing heart: effect of acute beta-adrenergic stimulation.

Signaling pathways underlying transition of cardiomyocyte growth from hyperplasia in fetal/newborn to hypertrophy in postnatal/adult hearts are not well understood. We have shown that beta-adrenergic receptor (beta-AR)-mediated regulation of neonatal cardiomyocyte proliferation involves p70 ribosomal protein S6 kinase (p70S6K). Here we examined the ontogeny of phosphoinositide 3-kinase (PI3K)/p70S6K signaling pathway in rat hearts and investigated the influence of beta-AR on this pathway during development. Cardiac PI3K and p70S6K1 activities were high in the embryonic day 20 fetus, decreased gradually postnatally, and were low in the adult. In contrast, p70S6K2 was barely detectable. Phosphorylation of p70S6K1, Akt, and phosphoinositide-dependent protein kinase 1 were markedly increased in late gestation and early postnatal life but not in adult hearts. Phosphatase and tensin homolog on chromosome 10 (PTEN), a negative regulator of PI3K, was highly expressed in adult hearts but only at low levels and mostly in the phosphorylated (inactivated) form in the fetus. Beta-AR stimulation resulted in increased cardiac p70S6K1 activity only in animals > or = 2 wk old, whereas Akt level was increased in all developmental stages tested. These increases were accompanied by increased Bcl-2 associated death promoter (Ser136) phosphorylation without changes in PTEN level. Thus there is globally high input of cardiac PI3K signaling during the fetal-neonatal transition period. Inactivation of PTEN may in part contribute to the high activity of PI3K signaling, which coincides with the period of high cardiomyocyte proliferation. Beta-AR stimulation activates cardiac p70S6K1 and Akt in postnatal animals and may activate cardiac survival signals. These data provide further evidence for the importance of beta-AR and PI3K signaling in the regulation of cardiac growth during development.

Adrenergic beta-Agonists↗

PubMed2004

Evidence for cyclin D3 as a novel target of rapamycin in human T lymphocytes.

The immunosuppressant rapamycin has been shown to inhibit G(1)/S transition of the cell cycle. This inhibition is thought to be mediated by maintenance of the threshold levels of cyclin-dependent kinase (CDK) inhibitor p27(Kip1) (p27) and inhibition of p70 s6 kinase (p70(s6k)). However, recent evidence suggests that cells still remain sensitive to rapamycin in the absence of functional p27 or p70(s6k). Here, we show that rapamycin represses cyclin D3 levels in activated human T lymphocytes with no inhibitory effects on cyclin D2. Furthermore, rapamycin elicits similar cyclin D3 modulatory effects in B lymphocytes. The overall effect of rapamycin on cyclin D3 leads to impaired formation of active complexes with Cdk4 or Cdk6 and subsequent inhibition of cyclin D3/CDK kinase activity. Decrease in cyclin D3 protein levels is due to translational repression and not due to attenuated transcription of the cyclin D3 gene. Importantly, stable overexpression of cyclin D3 (2-2.5 fold) in Jurkat T cell transfectants renders them resistant to lower doses (1-10 ng/ml) of rapamycin. These results point to a critical role of cyclin D3 in rapamycin-mediated immunosuppressive effects in T cells and cell cycle regulation in lymphocytes in general.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2003

Regulation of cardiac beta 1-adrenergic receptor transcription during the developmental transition.

The beta(1)-adrenergic receptor (beta(1)AR) gene contains binding sites for myc/max proteins within a glucocorticoid response element. Transcriptional activation of the beta(1)AR is the result of cooperative binding between c-myc and the glucocorticoid receptor on the beta(1)AR promoter. The transcriptional regulation of both beta(1)AR and c-myc are developmentally regulated. We used transcription rate assays of nuclei isolated from fetal hearts to demonstrate a fivefold increase in the transcription rate of beta(1)AR vs. postnatal hearts (P < 0.01). This was associated with a fourfold increase in c-myc transcription. Transcription rate assays performed in a rat fibroblast cell line that overexpresses c-myc (myc(+/+)) showed similarly increased beta(1)AR expression compared with the wild-type cell line. Transient transfection experiments in the myc(+/+) cells demonstrated robust expression of beta(1)AR promoter constructs, which was abrogated by mutation of the myc/max binding site or by cotransfection with a c-myc antisense expression vector. These results suggest that the regulation of cardiac beta(1)AR transcription and the expression of c-myc are tightly integrated.

Animals↗

PubMed2002

Molecular interactions between glucocorticoid and catecholamine signaling pathways.

To study the mechanism underlying glucocorticoid regulation of the beta(1)-adrenergic receptor (beta(1)AR), we identified a 43-bp region (-1274 to -1232 from the translation start site) that contains a novel glucocorticoid regulatory unit (GRU) that confers glucocorticoid responsiveness. The sequence encompassing the GRU is (5')TAATTA(3'), which is a core-binding motif for the homeodomain proteins; an E-box ((5')CACGTG(3')) binding site for the Myc/Max family proteins, and an overlapping glucocorticoid response element half-site ((5')TGTTCT(3')). We showed that the half-site is critical for GRU-protein interactions, which also require binding of proteins to the E-box and the homeodomain region. Expression of proteins binding to the GRU was shown to be developmentally regulated, being high in embryonic hearts, reduced in newborn hearts, and undetectable in adult hearts. Overexpression of c-myc antisense significantly reduced glucocorticoid responsiveness of the beta(1)AR gene. We further demonstrated that transcriptional regulation of the beta(1)AR gene is closely related to that of the c-myc gene and that the beta(1)AR may be a potential target of c-myc. We conclude that the ovine beta(1)AR gene contains a novel, functional GRU and that the nuclear factors that transactivate through this element may have important developmental implications.

Animals↗