published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

Abstract not available

<p>Plant natriuretic peptides (PNPs) are a novel class of extracellular, systemically mobile molecules that elicit a number of plant responses important in homeostasis and growth. Natriuretic peptides were first identified in vertebrates where they play a role in the regulation of salt and water balance. Subsequent experimental investigations have identified the presence of a natriuretic peptide hormone system in plants. While PNPs have been implicated in various physiological responses such as stomatal guard cell movements and regulation of net water uptake, its biological role has remained elusive. Here we have used co-expression and promoter content analysis tools to understand the biological role of the Arabidopsis thaliana PNP (AtPNP-A). The analysis of AtPNP-A and its co-expressed genes revealed that genes annotated as part of the systemic acquired resistance (SAR) pathway were over-represented, thus suggesting that AtPNP-A may function as a component of plant defense responses and specifically, SAR. The results further show that AtPNP-A shares many characteristics with pathogenesis related (PR) proteins in that its transcription is strongly induced in response to pathogen challenges, thus implying a newly described role for AtPNP-A in pathogen attack. Additional tissue expression analysis also indicated distinct localization of PNP activity in sepals and transcriptional meta-analysis showed that AtPNP-A may play a role in starch breakdown. Therefore, together with the finding that AtPNP-A plays a role in regulating phloem transport, we also hypothesize that AtPNP-A may play a role in phloem unloading in sepals to assist processes such as seed formation in plants. In plants, the second messenger, guanosine 3&rsquo / ,5&rsquo / -cyclic monophosphate (cGMP) mediates a whole range of important processes including salinity tolerance, disease resistance, drought tolerance and responses to light. Since PNPs regulate water and salt homeostasis via a cGMP-dependent signaling pathways, it is thus important to analyse the transcriptome induced by the second messenger (cGMP) in Arabidopsis thaliana to give a better understanding of its mechanism of action. This study was also supplemented by the analysis of the gibberellic acid (GA) dependent transcriptome, since cGMP also plays a role its transcription pathway. This data analysis, together with promoter content investigation, revealed that genes upregulated after cGMP treatment and down-regulated in the GA insensitive mutant (ga1-3) were enriched with a GA response element (GARE), while no GARE enrichment were observed in genes up-regulated in the ga1-3 mutant. These findings suggest that GARE is indicative of GA-induced and cGMP-dependent transcriptional up-regulation. Gene ontology analysis confirmed previous reports that cGMP is involved in ion homeostasis and indicated that the transcriptional cGMP response is bi-polar in the sense that both genes up- and down-regulated in response to cGMP is involved in cation transport. Additionally, ab initio analysis of genes transcriptionally dependent on cGMP identified CHX8 as a hub gene and promoter content of CHX8 co-expressed genes show enrichment of the GARE motif. The fact that CHX8 has its highest expression levels during male gametogenesis and pollen tube growth, together with our findings, suggest that GA-induced and cGMP- dependent genes may play a key role in ion and water homeostasis in the male gametophyte. Finally, we propose that the type of analysis undertaken here can yield new insights into gene regulation networks and inform experimental strategies to unravel complex transcription regulatory systems under different developmental and stimulus specific conditions.</p>

Some aspects of the stress response during acute intensive care for severe burns are described and quantified by measuring hormonal and neuroendocrine patterns and relating these to organ function in the short term. This includes an assessment of whether there are markers for the severity of stress that are better than conventional descriptors of the severity of a burn in predicting failing organ function. P-CgA after a major burn injury is an independent and better predictor of organ dysfunction assessed as SOFA score than the traditionally used TBSA% burned. The results also suggest that the extent of neuroendocrine activation is related to organ dysfunction, and this motivates a more extensive effort to evaluate P-CgA as a prognostic marker with respect to mortality and long-term outcome. P-NT-proBNP exhibited a complex pattern with considerable inter-individual and day-to-day variations. Values of P-NT-proBNP were related to size of burn, water accumulation and systemic inflammatory response. A considerable covariation with trauma response and SOFA scores was observed in day by day analyses, but with weight change only on day 2. Maximum P-NT-proBNP showed a stronger correlation with SOFA score on day 14, with mortality, and with LOS, than did age and TBSA% burned. High values were also independent predictors of all subsequent SOFA scores up to two weeks after injury. P-NT-proBNP and NT-proANP reflect and predict organ function after burn injury similarly, notwithstanding a significantly larger intra-individual variability for P-NT-proBNP. P-NT-proBNP, but not NT-proANP, reflects the systemic inflammatory trauma response. Free cortisol concentration was related to the size of burns, as was the circadian cortisol rhythm. This effect of burn size was, at least in part, related to its effect on organ function. This thesis points to the fact that the stress response is richly interwoven, and cannot be adequately assessed by one biomarker only. All biomarkers studied here can be viewed as representing efferent limbs of the stress reaction, and they would need to be supplemented by biomarkers representing individual physiologic responses that follow the stress signaling.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

<p>Plant natriuretic peptides (PNPs) are a novel class of extracellular, systemically mobile molecules that elicit a number of plant responses important in homeostasis and growth. Natriuretic peptides were first identified in vertebrates where they play a role in the regulation of salt and water balance. Subsequent experimental investigations have identified the presence of a natriuretic peptide hormone system in plants. While PNPs have been implicated in various physiological responses such as stomatal guard cell movements and regulation of net water uptake, its biological role has remained elusive. Here we have used co-expression and promoter content analysis tools to understand the biological role of the Arabidopsis thaliana PNP (AtPNP-A). The analysis of AtPNP-A and its co-expressed genes revealed that genes annotated as part of the systemic acquired resistance (SAR) pathway were over-represented, thus suggesting that AtPNP-A may function as a component of plant defense responses and specifically, SAR. The results further show that AtPNP-A shares many characteristics with pathogenesis related (PR) proteins in that its transcription is strongly induced in response to pathogen challenges, thus implying a newly described role for AtPNP-A in pathogen attack. Additional tissue expression analysis also indicated distinct localization of PNP activity in sepals and transcriptional meta-analysis showed that AtPNP-A may play a role in starch breakdown. Therefore, together with the finding that AtPNP-A plays a role in regulating phloem transport, we also hypothesize that AtPNP-A may play a role in phloem unloading in sepals to assist processes such as seed formation in plants. In plants, the second messenger, guanosine 3&rsquo / ,5&rsquo / -cyclic monophosphate (cGMP) mediates a whole range of important processes including salinity tolerance, disease resistance, drought tolerance and responses to light. Since PNPs regulate water and salt homeostasis via a cGMP-dependent signaling pathways, it is thus important to analyse the transcriptome induced by the second messenger (cGMP) in Arabidopsis thaliana to give a better understanding of its mechanism of action. This study was also supplemented by the analysis of the gibberellic acid (GA) dependent transcriptome, since cGMP also plays a role its transcription pathway. This data analysis, together with promoter content investigation, revealed that genes upregulated after cGMP treatment and down-regulated in the GA insensitive mutant (ga1-3) were enriched with a GA response element (GARE), while no GARE enrichment were observed in genes up-regulated in the ga1-3 mutant. These findings suggest that GARE is indicative of GA-induced and cGMP-dependent transcriptional up-regulation. Gene ontology analysis confirmed previous reports that cGMP is involved in ion homeostasis and indicated that the transcriptional cGMP response is bi-polar in the sense that both genes up- and down-regulated in response to cGMP is involved in cation transport. Additionally, ab initio analysis of genes transcriptionally dependent on cGMP identified CHX8 as a hub gene and promoter content of CHX8 co-expressed genes show enrichment of the GARE motif. The fact that CHX8 has its highest expression levels during male gametogenesis and pollen tube growth, together with our findings, suggest that GA-induced and cGMP- dependent genes may play a key role in ion and water homeostasis in the male gametophyte. Finally, we propose that the type of analysis undertaken here can yield new insights into gene regulation networks and inform experimental strategies to unravel complex transcription regulatory systems under different developmental and stimulus specific conditions.</p>

No description available.

Thesis (M. Med. Sc.)--University of Hong Kong, 2005.

Abstract Cardiac pathologies, including ventricular hypertrophy, are the primary cause of death in industrialized countries. Cardiac hypertrophy is often the consequence of work overload on the heart and characterizes several cardiovascular diseases, including atherosclerosis and hypertension. Cardiac hypertrophy is accompanied by genetic reprogramming characterized by the reexpression of several embryonic and growth response genes. Two of these genes encode A- and B-type natriuretic peptides (ANP and BNP), two cardiac-specific hormones secreted by myocytes, which play an important role in blood pressure regulation. The aim of the present study was to study the effect of acute pressure overload on BNP gene expression in the hearts of normal and hypertensive rats and then to examine the role of a passerine factor, angiotensin II (Ang II), on volume and pressure overload -induced ANP and BNP secretion and synthesis. Further, the aim was to characterize elements on the BNP promoter mediating hemodynamic stress in vivo. BNP gene expression was studied in conscious spontaneously hypertensive (SHR) rats and together with ANP in two hypertensive, ream Transgenic rat models. The increased workload of the heart was produced by the infusion of vasopressin (AVP), phenylephrine (PHE) or bolus saline infusion. The increased workload caused rapid increases in cardiac BNP mRNA levels. Daring both AVP and PHE infusions, substantial increases in ventricular BNP mRNA levels were already evident after I h, and peak levels of BNP mRNA were reached at 4 h. Transgenic rats carrying one extra mouse renin gene showed impaired secretion and synthesis of ANP and BNP, while double transgenic rats carrying both human angiotensinogen and human renin genes showed augmentation of left atrial, but not ventricular BNP gene expression in response ta acute pressure overload. To characterize the elements mediating hemodynamic stress, bi-lateral nephrectomy was performed. GATA motif transduced the hemodynamic stress stimulus 26–28 hrs postnephrectomy in BNP gene expression.In conclusion, these results show that pressure overload abruptly stimulates the cardiac expression of a noncontractile protein gene BNP, suggesting that it may be used as a myocyte-specific marker of mechanical loading. BNP gene expression was augmented in atria hut nut in ventricles in response to pressure overload in an experimental model of hypertension, suggesting that high local levels of Ang II may differentially regulate cardiac gene expression in atrial and ventricular myocytes in double transgenic rats. At the transcriptional level, acute hemodynamic stress produced by nephrectomy increases BNP reporter expression through a GATA-dependent pathway.

Abstract The natriuretic peptides are a family of hormones secreted by the heart. They play a fundamental role in salt and water balance and blood pressure regulation. Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) are the known members of the mammalian natriuretic peptide family. A major stimulus for the secretion of cardiac natriuretic peptides is myocyte stretch. Therefore, the secretion of natriuretic peptides is increased in response to elevated blood volume. Natriuretic peptide production and release is also affected by several other factors, such as endothelin-1 (ET-1), acting in paracrine fashion. The aim of this study was to elucidate factors regulating the novel cardiac peptide hormone, salmon cardiac peptide (sCP), belonging to the family of natriuretic peptides. The role of mechanical load, temperature and ET-1 in sCP secretion and production was studied using in vitro (isolated perfused ventricle preparation) and in vivo methods. Comparisons between the natriuretic peptide systems in fish and mammals were done to clarify functional evolution of this hormone family. Salmon (Salmo salar) was selected as a model, since it has an outstanding adaptability to wide variations in environmental salinity and has developed defence mechanisms against volume or salt load. The results showed that salmon ventricle stores large amounts of the prohormone of sCP, whereas the secreted form is the mature 29-amino acid form. The N-terminal fragment of pro-sCP is co-secreted with sCP in equimolar amounts. sCP is released rapidly in response to appropriate stimulus, whereas induction of its gene expression is slower. Mechanical load is an important regulator of sCP secretion. Temperature also plays a major role in regulating sCP plasma concentration by affecting its elimination from circulation. Additionally, ET-1 is a potent secretagogue of the sCP system and an inotropic agent in salmon heart. Furthermore, the present results reveal remarkable synergism between the cardiac effects of ET-1 and β-adrenergic stimulation. In conclusion, the sCP system in salmon ventricle largely resembles the ANP system in mammalian atrium, while also having specific characteristics, such as a regulated ventricular natriuretic peptide secretion pathway. Therefore, the sCP system offers a unique model for studying mechanisms of natriuretic peptide biology.