HIF-1 alpha response to hypoxia is functionally separated from the glucocorticoid stress response in the in vitro regenerating human skeletal muscle
Апстракт
Pirkmajer S, Filipovic D, Mars T, Mis K, Grubic Z. HIF-1 alpha response to hypoxia is functionally separated from the glucocorticoid stress response in the in vitro regenerating human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 299: R1693-R1700, 2010. First published October 13, 2010; doi:10.1152/ajpregu.00133.2010.-Injury of skeletal muscle is followed by muscle regeneration in which new muscle tissue is formed from the proliferating mononuclear myoblasts, and by systemic response to stress that exposes proliferating myoblasts to increased glucocorticoid (GC) concentration. Because of its various causes, hypoxia is a frequent condition affecting skeletal muscle, and therefore both processes, which importantly determine the outcome of the injury, often proceed under hypoxic conditions. It is therefore important to identify and characterize in proliferating human myoblasts: 1) response to hypoxia which is generally organized by hypoxia-inducible factor-1 alpha (HIF-1 alpha);... 2) response to GCs which is mediated through the isoforms of glucocorticoid receptors (GRs) and 11 beta-hydroxysteroid dehydrogenases (11 beta-HSDs), and 3) the response to GCs under the hypoxic conditions and the influence of this combination on the factors controlling myoblast proliferation. Using real-time PCR, Western blotting, and HIF-1 alpha small-interfering RNA silencing, we demonstrated that cultured human myoblasts possess both, the HIF-1 alpha-based response to hypoxia, and the GC response system composed of GR alpha and types 1 and 2 11 beta-HSDs. However, using combined dexamethasone and hypoxia treatments, we demonstrated that these two systems operate practically without mutual interactions. A seemingly surprising separation of the two systems that both organize response to hypoxic stress can be explained on the evolutionary basis: the phylogenetically older HIF-1 alpha response is a protection at the cellular level, whereas the GC stress response protects the organism as a whole. This necessitates actions, like downregulation of IL-6 secretion and vascular endothelial growth factor, that might not be of direct benefit for the affected myoblasts.
Кључне речи:
hypoxia-inducible factor-alpha / antisense version of hypoxia-inducible factor / vascular endothelial growth factor / glucocorticoid receptors / 11 beta-hydroxysteroid dehydrogenasesИзвор:
American Journal of Physiology: Regulatory Integrative and Comparative Physiology, 2010, 299, 6, R1693-R1700Финансирање / пројекти:
- Slovenian Research Agency, Federation of European Biochemical Societies, Ad Futura Agency of Slovenia
DOI: 10.1152/ajpregu.00133.2010
ISSN: 0363-6119
PubMed: 20943857
WoS: 000285047000030
Scopus: 2-s2.0-78649851593
Колекције
Институција/група
VinčaTY - JOUR AU - Pirkmajer, Sergej AU - Filipović, Dragana AU - Mars, Tomaz AU - Mis, Katarina AU - Grubic, Zoran PY - 2010 UR - https://vinar.vin.bg.ac.rs/handle/123456789/4162 AB - Pirkmajer S, Filipovic D, Mars T, Mis K, Grubic Z. HIF-1 alpha response to hypoxia is functionally separated from the glucocorticoid stress response in the in vitro regenerating human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 299: R1693-R1700, 2010. First published October 13, 2010; doi:10.1152/ajpregu.00133.2010.-Injury of skeletal muscle is followed by muscle regeneration in which new muscle tissue is formed from the proliferating mononuclear myoblasts, and by systemic response to stress that exposes proliferating myoblasts to increased glucocorticoid (GC) concentration. Because of its various causes, hypoxia is a frequent condition affecting skeletal muscle, and therefore both processes, which importantly determine the outcome of the injury, often proceed under hypoxic conditions. It is therefore important to identify and characterize in proliferating human myoblasts: 1) response to hypoxia which is generally organized by hypoxia-inducible factor-1 alpha (HIF-1 alpha); 2) response to GCs which is mediated through the isoforms of glucocorticoid receptors (GRs) and 11 beta-hydroxysteroid dehydrogenases (11 beta-HSDs), and 3) the response to GCs under the hypoxic conditions and the influence of this combination on the factors controlling myoblast proliferation. Using real-time PCR, Western blotting, and HIF-1 alpha small-interfering RNA silencing, we demonstrated that cultured human myoblasts possess both, the HIF-1 alpha-based response to hypoxia, and the GC response system composed of GR alpha and types 1 and 2 11 beta-HSDs. However, using combined dexamethasone and hypoxia treatments, we demonstrated that these two systems operate practically without mutual interactions. A seemingly surprising separation of the two systems that both organize response to hypoxic stress can be explained on the evolutionary basis: the phylogenetically older HIF-1 alpha response is a protection at the cellular level, whereas the GC stress response protects the organism as a whole. This necessitates actions, like downregulation of IL-6 secretion and vascular endothelial growth factor, that might not be of direct benefit for the affected myoblasts. T2 - American Journal of Physiology: Regulatory Integrative and Comparative Physiology T1 - HIF-1 alpha response to hypoxia is functionally separated from the glucocorticoid stress response in the in vitro regenerating human skeletal muscle VL - 299 IS - 6 SP - R1693 EP - R1700 DO - 10.1152/ajpregu.00133.2010 ER -
@article{ author = "Pirkmajer, Sergej and Filipović, Dragana and Mars, Tomaz and Mis, Katarina and Grubic, Zoran", year = "2010", abstract = "Pirkmajer S, Filipovic D, Mars T, Mis K, Grubic Z. HIF-1 alpha response to hypoxia is functionally separated from the glucocorticoid stress response in the in vitro regenerating human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 299: R1693-R1700, 2010. First published October 13, 2010; doi:10.1152/ajpregu.00133.2010.-Injury of skeletal muscle is followed by muscle regeneration in which new muscle tissue is formed from the proliferating mononuclear myoblasts, and by systemic response to stress that exposes proliferating myoblasts to increased glucocorticoid (GC) concentration. Because of its various causes, hypoxia is a frequent condition affecting skeletal muscle, and therefore both processes, which importantly determine the outcome of the injury, often proceed under hypoxic conditions. It is therefore important to identify and characterize in proliferating human myoblasts: 1) response to hypoxia which is generally organized by hypoxia-inducible factor-1 alpha (HIF-1 alpha); 2) response to GCs which is mediated through the isoforms of glucocorticoid receptors (GRs) and 11 beta-hydroxysteroid dehydrogenases (11 beta-HSDs), and 3) the response to GCs under the hypoxic conditions and the influence of this combination on the factors controlling myoblast proliferation. Using real-time PCR, Western blotting, and HIF-1 alpha small-interfering RNA silencing, we demonstrated that cultured human myoblasts possess both, the HIF-1 alpha-based response to hypoxia, and the GC response system composed of GR alpha and types 1 and 2 11 beta-HSDs. However, using combined dexamethasone and hypoxia treatments, we demonstrated that these two systems operate practically without mutual interactions. A seemingly surprising separation of the two systems that both organize response to hypoxic stress can be explained on the evolutionary basis: the phylogenetically older HIF-1 alpha response is a protection at the cellular level, whereas the GC stress response protects the organism as a whole. This necessitates actions, like downregulation of IL-6 secretion and vascular endothelial growth factor, that might not be of direct benefit for the affected myoblasts.", journal = "American Journal of Physiology: Regulatory Integrative and Comparative Physiology", title = "HIF-1 alpha response to hypoxia is functionally separated from the glucocorticoid stress response in the in vitro regenerating human skeletal muscle", volume = "299", number = "6", pages = "R1693-R1700", doi = "10.1152/ajpregu.00133.2010" }
Pirkmajer, S., Filipović, D., Mars, T., Mis, K.,& Grubic, Z.. (2010). HIF-1 alpha response to hypoxia is functionally separated from the glucocorticoid stress response in the in vitro regenerating human skeletal muscle. in American Journal of Physiology: Regulatory Integrative and Comparative Physiology, 299(6), R1693-R1700. https://doi.org/10.1152/ajpregu.00133.2010
Pirkmajer S, Filipović D, Mars T, Mis K, Grubic Z. HIF-1 alpha response to hypoxia is functionally separated from the glucocorticoid stress response in the in vitro regenerating human skeletal muscle. in American Journal of Physiology: Regulatory Integrative and Comparative Physiology. 2010;299(6):R1693-R1700. doi:10.1152/ajpregu.00133.2010 .
Pirkmajer, Sergej, Filipović, Dragana, Mars, Tomaz, Mis, Katarina, Grubic, Zoran, "HIF-1 alpha response to hypoxia is functionally separated from the glucocorticoid stress response in the in vitro regenerating human skeletal muscle" in American Journal of Physiology: Regulatory Integrative and Comparative Physiology, 299, no. 6 (2010):R1693-R1700, https://doi.org/10.1152/ajpregu.00133.2010 . .