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Vincent Healy

Publications and source records attributed to Vincent Healy.

4 recordsLinked to original sources
PubMed2005

17beta-Estradiol rapidly stimulates c-fos expression via the MAPK pathway in T84 cells.

In this study, we show that 17beta-Estradiol (E2) induced the proliferation of T84 colonic carcinoma cells. We, further, investigated the mechanisms underlying this proliferation and show that E2 induced c-fos protooncogene expression in T84 cells in a timescale consistent with a rapid non-genomic action of the hormone. Furthermore, E2 rapidly phosphorylated both CREB and ELK1, transcription factors that bind to the c-fos promoter and stimulate transcription. Pretreatment with PD98059 and H89, mitogen-activated protein kinase (MAPK) pathway and protein kinase A (PKA) inhibitors, respectively showed that phosphorylation of CREB and ELK1 and subsequent c-fos induction was mediated by the MAPK pathway only. Finally, the estrogen receptor (ER) antagonist, ICI 182,780, blocked the activation of MAPK pathway, subsequent CREB and ELK1 phosphorylation and c-fos induction in T84 cells suggesting an ER dependent mechanism. Consistent with this finding, ICI 182,780 caused a substantial reduction in the proliferative effects of E2 on T84 cells.

Antineoplastic Agents↗
PubMed2005

Aldosterone rapidly activates Na+/H+ exchange in M-1 cortical collecting duct cells via a PKC-MAPK pathway.

BACKGROUND: In this study, the mechanism of the rapid non-genomic effect of aldosterone on Na(+)/H(+) exchanger (NHE)-mediated intracellular pH (pH(i)) recovery from an acid load in murine M-1 cortical collecting duct cells was assessed. METHODS: Spectrofluorescence microscopy and Western blot analysis was carried out and NH(4)Cl was used to induce the acid load. RESULTS: Aldosterone (10 nM) induced a rapid (<5 min) concentration-dependent increase in pH(i) recovery in M-1 cells, an effect mimicked by its precursor deoxycorticosterone (1 nM). This response was unaffected by the mineralocorticoid receptor (MR) antagonist spironolactone (10 microM) but was significantly reduced by the NHE antagonists 5'-(N-ethyl- N-isopropyl)amiloride (EIPA) (20 microM) and cariporide (1 microM). The PKC inhibitor chelerythrine chloride (1 microM) significantly attenuated the aldosterone-induced increase in NHE1 activity. HBDDE (80 microM), a PKC(alpha) inhibitor, inhibited the rapid aldosterone effect whereas rottlerin (15 microM), a PKC(delta) antagonist, did not. The glucocorticoid receptor agonists hydrocortisone (1 microM) and dexamethasone (100 nM) decreased NHE activity, whereas the synthetic mineralocorticoid fludrocortisone (1 nM) had no significant effect. MAPK inhibition using PD98059 (25 microM) significantly attenuated the rapid aldosterone effect; Western blot analysis showed that aldosterone activation of ERK 1/2 was unaffected by pretreatment with spironolactone but was inhibited following chelerythrine chloride. CONCLUSION: Aldosterone causes a rapid non-genomic increase in NHE1 activity in M-1 cells via a PKC(alpha )/MAPK pathway independent of the classical MR.

Aldosterone↗
PubMed2002

Rapid responses to steroid hormones: from frog skin to human colon. A homage to Hans Ussing.

Fifty years ago, Hans Ussing described the mechanism by which ions are actively transported across frog skin. Since then, an enormous amount of effort has been invested in determining the cellular and molecular specifics of the transport mechanisms and their regulatory pathways. Ion transport in high-resistance epithelia is regulated by a variety of hormonal and non-hormonal factors. In vertebrates, steroid hormones such as mineralocorticoids, glucocorticoids and estrogens are major regulators of ion and water transport and hence are central to the control of extracellular fluid volume and blood pressure. Steroid hormones act through nuclear receptors to control the transcriptional activity of specific target genes, such as ion channels, ion transporters and ion pumps. These effects are observed after a latency of several hours and can last for days leading to cellular differentiation that allows a higher transport activity. This pathway is the so-called genomic phase. However, in the past 10 years, it has become apparent that steroid hormones can regulate electrolyte and water transport in tight epithelia independently of the transcription of these ion channels and transporters by regulating ion transporter activity in a non-genomic fashion via modulation of various signal transduction pathways. The molecular mechanisms underlying the steroid hormone-induced activation of signal transduction pathways such as protein kinase C (PKC), protein kinase A (PKA), intracellular calcium, intracellular pH and mitogen-activated protein kinases (MAPKs) and how non-genomic activation of these pathways influences epithelial ion transport will be discussed in this review.

Animals↗