pPKCα mediated-HIF-1α activation related to the morphological modifications occurring in neonatal myocardial tissue in response to severe and mild hyperoxia
In premature babies birth an high oxygen level exposure can occur and newborn hyperoxia exposure can be associated with free radical oxygen release with impairment of myocardial function, while in adult animal models short exposure to hyperoxia seems to protect heart against ischemic injury. Thus,...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
PAGEPress Publications
2012-01-01
|
| Series: | European Journal of Histochemistry |
| Subjects: | |
| Online Access: | http://www.ejh.it/index.php/ejh/article/view/1929 |
| _version_ | 1818749777578295296 |
|---|---|
| author | S. Zara V. Macchi R. De Caro M. Rapino A. Cataldi A. Porzionato |
| author_facet | S. Zara V. Macchi R. De Caro M. Rapino A. Cataldi A. Porzionato |
| author_sort | S. Zara |
| collection | DOAJ |
| description | In premature babies birth an high oxygen level exposure can occur and newborn hyperoxia exposure can be associated with free radical oxygen release with impairment of myocardial function, while in adult animal models short exposure to hyperoxia seems to protect heart against ischemic injury. Thus, the mechanisms and consequences which take place after hyperoxia exposure are different and related to animals age. The aim of our work has been to analyze the role played by HIF-1α in the occurrence of the morphological modifications upon hyperoxia exposure in neonatal rat heart. Hyperoxia exposure induces connective compartment increase which seems to allow enhanced blood vessels growth. An increased hypoxia inducible factor-1α (HIF-1α) translocation and vascular endothelial growth factor (VEGF) expression has been found upon 95% oxygen exposure to induce morphological modifications. Upstream pPKC-α expression increase in newborn rats exposed to 95% oxygen can suggest PKC involvement in HIF-1α activation. Since nitric oxide synthase (NOS) are involved in heart vascular regulation, endothelial NOS (e-NOS) and inducible NOS (i-NOS) expression has been investigated: a lower eNOS and an higher iNOS expression has been found in newborn rats exposed to 95% oxygen related to the evidence that hyperoxia provokes a systemic vasoconstriction and to the iNOS pro-apoptotic action, respectively. The occurrence of apoptotic events, evaluated by TUNEL and Bax expression analyses, seems more evident in sample exposed to severe hyperoxia. All in all such results suggest that in newborn rats hyperoxia can trigger oxygen free radical mediated membrane injury through a pPKCα mediated HIF-1α signalling system, even though specificity of such response could be obtained by <em>in vivo</em> administration to the rats of specific inhibitors of PKCα. This intracellular signalling can switch molecular events leading to blood vessels development in parallel to pro-apoptotic events due to an immature anti-oxidant defensive system in newborn rat hearts. |
| first_indexed | 2024-12-18T04:09:10Z |
| format | Article |
| id | doaj.art-12a28cd705ec40d7bd66e7b66a7a7adb |
| institution | Directory Open Access Journal |
| issn | 1121-760X 2038-8306 |
| language | English |
| last_indexed | 2024-12-18T04:09:10Z |
| publishDate | 2012-01-01 |
| publisher | PAGEPress Publications |
| record_format | Article |
| series | European Journal of Histochemistry |
| spelling | doaj.art-12a28cd705ec40d7bd66e7b66a7a7adb2022-12-21T21:21:30ZengPAGEPress PublicationsEuropean Journal of Histochemistry1121-760X2038-83062012-01-01561e2e210.4081/ejh.2012.e21246pPKCα mediated-HIF-1α activation related to the morphological modifications occurring in neonatal myocardial tissue in response to severe and mild hyperoxiaS. Zara0V. Macchi1R. De Caro2M. Rapino3A. Cataldi4A. Porzionato5University “G. d’Annunzio” Chieti-PescaraUniversity of PaduaUniversity of PaduaInstitute of Molecular Genetics CNRUniversity “G. d’Annunzio” Chieti-PescaraUniversity of PaduaIn premature babies birth an high oxygen level exposure can occur and newborn hyperoxia exposure can be associated with free radical oxygen release with impairment of myocardial function, while in adult animal models short exposure to hyperoxia seems to protect heart against ischemic injury. Thus, the mechanisms and consequences which take place after hyperoxia exposure are different and related to animals age. The aim of our work has been to analyze the role played by HIF-1α in the occurrence of the morphological modifications upon hyperoxia exposure in neonatal rat heart. Hyperoxia exposure induces connective compartment increase which seems to allow enhanced blood vessels growth. An increased hypoxia inducible factor-1α (HIF-1α) translocation and vascular endothelial growth factor (VEGF) expression has been found upon 95% oxygen exposure to induce morphological modifications. Upstream pPKC-α expression increase in newborn rats exposed to 95% oxygen can suggest PKC involvement in HIF-1α activation. Since nitric oxide synthase (NOS) are involved in heart vascular regulation, endothelial NOS (e-NOS) and inducible NOS (i-NOS) expression has been investigated: a lower eNOS and an higher iNOS expression has been found in newborn rats exposed to 95% oxygen related to the evidence that hyperoxia provokes a systemic vasoconstriction and to the iNOS pro-apoptotic action, respectively. The occurrence of apoptotic events, evaluated by TUNEL and Bax expression analyses, seems more evident in sample exposed to severe hyperoxia. All in all such results suggest that in newborn rats hyperoxia can trigger oxygen free radical mediated membrane injury through a pPKCα mediated HIF-1α signalling system, even though specificity of such response could be obtained by <em>in vivo</em> administration to the rats of specific inhibitors of PKCα. This intracellular signalling can switch molecular events leading to blood vessels development in parallel to pro-apoptotic events due to an immature anti-oxidant defensive system in newborn rat hearts.http://www.ejh.it/index.php/ejh/article/view/1929HIF-1α, pPKCα, neonatal myocardial tissue, hyperoxia |
| spellingShingle | S. Zara V. Macchi R. De Caro M. Rapino A. Cataldi A. Porzionato pPKCα mediated-HIF-1α activation related to the morphological modifications occurring in neonatal myocardial tissue in response to severe and mild hyperoxia European Journal of Histochemistry HIF-1α, pPKCα, neonatal myocardial tissue, hyperoxia |
| title | pPKCα mediated-HIF-1α activation related to the morphological modifications occurring in neonatal myocardial tissue in response to severe and mild hyperoxia |
| title_full | pPKCα mediated-HIF-1α activation related to the morphological modifications occurring in neonatal myocardial tissue in response to severe and mild hyperoxia |
| title_fullStr | pPKCα mediated-HIF-1α activation related to the morphological modifications occurring in neonatal myocardial tissue in response to severe and mild hyperoxia |
| title_full_unstemmed | pPKCα mediated-HIF-1α activation related to the morphological modifications occurring in neonatal myocardial tissue in response to severe and mild hyperoxia |
| title_short | pPKCα mediated-HIF-1α activation related to the morphological modifications occurring in neonatal myocardial tissue in response to severe and mild hyperoxia |
| title_sort | ppkcα mediated hif 1α activation related to the morphological modifications occurring in neonatal myocardial tissue in response to severe and mild hyperoxia |
| topic | HIF-1α, pPKCα, neonatal myocardial tissue, hyperoxia |
| url | http://www.ejh.it/index.php/ejh/article/view/1929 |
| work_keys_str_mv | AT szara ppkcamediatedhif1aactivationrelatedtothemorphologicalmodificationsoccurringinneonatalmyocardialtissueinresponsetosevereandmildhyperoxia AT vmacchi ppkcamediatedhif1aactivationrelatedtothemorphologicalmodificationsoccurringinneonatalmyocardialtissueinresponsetosevereandmildhyperoxia AT rdecaro ppkcamediatedhif1aactivationrelatedtothemorphologicalmodificationsoccurringinneonatalmyocardialtissueinresponsetosevereandmildhyperoxia AT mrapino ppkcamediatedhif1aactivationrelatedtothemorphologicalmodificationsoccurringinneonatalmyocardialtissueinresponsetosevereandmildhyperoxia AT acataldi ppkcamediatedhif1aactivationrelatedtothemorphologicalmodificationsoccurringinneonatalmyocardialtissueinresponsetosevereandmildhyperoxia AT aporzionato ppkcamediatedhif1aactivationrelatedtothemorphologicalmodificationsoccurringinneonatalmyocardialtissueinresponsetosevereandmildhyperoxia |