Wyniki wyszukiwania - Biblioteka Nauki

1

Effects of protoporphyrins on production of nitric oxide and expression of vascular endothelial growth factor in vascular smooth muscle cells and macrophages.

100%

Józkowicz A. , Dulak J.

Acta Biochimica Polonica

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2003

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tom 50

|

nr 1

69-79

EN

Heme oxygenase-1 (HO-1), an inducible enzyme degrading heme to biliverdin, iron and carbon monoxide, is involved in regulation of inflammation and angiogenesis. Tin protoporphyrin (SnPPIX) and zinc protoporphyrin (ZnPPIX) are commonly used as competitive inhibitors of HO-1. We aimed to compare the effects of SnPPIX and ZnPPIX on the production of vascular endothelial growth factor (VEGF), activity of inducible nitric oxide synthase (iNOS) and cell viability. All experiments were performed on rat vascular smooth muscle cells and murine RAW264.7 macrophages treated with 3-10 μM protoporphyrins. Some cells were additionally stimulated with IL-1β or with lipopolysaccharide. After a 24 h incubation period SnPPIX and ZnPPIX significantly reduced the generation of VEGF in vascular smooth muscle cells and RAW264.7, both in resting and stimulated cells. The inhibitory potentials of both protoporphyrins on VEGF synthesis were very similar. In contrast, analysis of iNOS activity revealed that results obtained with different HO-1 inhibitors are discrepant. Generation of nitric oxide by iNOS was significantly increased by SnPPIX but strongly decreased by ZnPPIX. Similar differences were observed when cell viability was compared. SnPPIX improved the cell survival rate, whereas the same doses of ZnPPIX exerted some cytotoxic effects. In summary, SnPPIX and ZnPPIX can be used as HO-1 inhibitors in some experimental models. However, these compounds produce also HO-independent effects, which can make the interpretation of experiments very uncertain. Thus the involvement of the HO-1 pathway should be always confirmed by more specific methods.

2

HIF-1: the knowns and unknowns of hypoxia sensing.

86%

Zagórska A. , Dulak J.

Acta Biochimica Polonica

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2004

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tom 51

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nr 3

563-585

EN

Hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator that functions as a master regulator of cellular and systemic oxygen homeostasis. It consists of two constitutively produced subunits: HIF-1α and HIF-1β. Under normoxic conditions HIF-1α undergoes hydroxylation at specific prolyl residues which leads to an immediate ubiquitination and subsequent proteasomal degradation of the α subunit. Additionally, hydroxylation of an asparaginyl residue blocks the transcriptional activity of HIF-1 due to inhibition of its interaction with co-activators. In contrast, under hypoxic conditions, abolition of prolyl hydroxylation results in HIF-1α stabilization, whereas the lack of asparaginyl hydroxylation allows the transcriptional activity. Additionally, the transcriptional activity may be modulated by phosphorylation or redox modification of HIF-1. Despite its name, HIF-1 is induced not only in response to reduced oxygen availability but also by other stimulants, such as nitric oxide, various growth factors, or direct inhibitors of prolyl and asparaginyl hydroxylases. Therefore, it seems to be a crucial transcription factor elicited by a wide range of stresses such as impaired oxygenation, inflammation, energy deprivation, or intensive proliferation. However, the mechanisms of normoxic activation, as well as of oxygen sensing, are not yet fully known. Further understanding of the processes that control HIF-1 activity will be crucial for the development of new diagnostic and therapeutic strategies.

3

Heme oxygenase-1 expression in disease states

86%

Deshane J. , Wright M. , Agarwal A.

Acta Biochimica Polonica

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2005

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tom 52

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nr 2

EN

Heme oxygenase-1 (HO-1) is an enzyme which catalyzes the rate-limiting step in heme degradation resulting in the formation of iron, carbon monoxide and biliverdin, which is subsequently converted to bilirubin by biliverdin reductase. The biological effects exerted by the products of this enzymatic reaction have gained much attention. The anti-oxidant, anti-inflammatory and cytoprotective functions associated with HO-1 are attributable to one or more of its degradation products. Induction of HO-1 occurs as an adaptive and beneficial response to several injurious stimuli including heme and this inducible nature of HO-1 signifies its importance in several pathophysiological disease states. The beneficial role of HO-1 has been implicated in several clinically relevant disease states involving multiple organ systems as well as significant biological processes such as ischemia-reperfusion injury, inflammation/immune dysfunction and transplantation. HO-1 has thus emerged as a key target molecule with therapeutic implications.

4

Effects of protoporphyrins on production of nitric oxide and expression of vascular endothelial growth factor in vascular smooth muscle cells and macrophages

86%

Jozkowicz A. , Dulak J.

|

nr 1

EN

Heme oxygenase-1 (HO-1), an inducible enzyme degrading heme to biliverdin, iron and carbon monoxide, is involved in regulation of inflammation and angiogenesis. Tin protoporphyrin (SnPPIX) and zinc protoporphyrin (ZnPPIX) are commonly used as competitive inhibitors of HO-1. We aimed to compare the effects of SnPPIX and ZnPPIX on the production of vascular endothelial growth factor (VEGF), activity of inducible nitric oxide synthase (iNOS) and cell viability. All experiments were performed on rat vascular smooth muscle cells and murine RAW264.7 macrophages treated with 3-10 ,uM protoporphyrins. Some cells were additionally stimulated with IL-1β or with lipopolysaccharide. After a 24 h incubation period SnPPIX and ZnPPIX significantly reduced the generation of VEGF in vascular smooth muscle cells and RAW264.7, both in resting and stimulated cells. The inhibitory potentials of both protoporphyrins on VEGF synthesis were very similar. In contrast, analysis of iNOS activity revealed that results obtained with different HO-1 inhibitors are discrepant.

5

The role of nitric oxide synthase, superoxide dismutase and heme oxygenase-1 in the synthesis of vascular endothelial growth factor

86%

Dulak J. , Grzenkowicz J. , Cisowski J. , Podhajska A. , Jozkowicz A.

Cellular and Molecular Biology Letters

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2002

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tom 07

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nr Suppl.

6

Carbon monoxide-mediated humoral pathway for the transmission of light signal to the hypothalamus

72%

Gilun P. , Stefanczyk-Krzymowska S. , Romerowicz-Misielak M. , Tabecka-Lonczynska A. , Przekop F. , Koziorowski M.

Journal of Physiology and Pharmacology

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2013

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tom 64

|

nr 6

7

HIF-1: the knowns and unknowns of hypoxia sensing

72%

Zagorska A. , Dulak J.

Acta Biochimica Polonica

|

2004

|

tom 51

|

nr 3

EN

Hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator that functions as a master regulator of cellular and systemic oxygen homeostasis. It consists of two con- stitutively produced subunits: HIF-1a and HIF-1ß. Under normoxic conditions HIF-1a undergoes hydroxylation at specific prolyl residues which leads to an immediate ubiquitination and subsequent proteasomal degradation of the a subunit. Additionally, hydroxylation of an asparaginyl residue blocks the transcriptional activity of HIF-1 due to inhibition of its interaction with co-activators. In contrast, under hypoxic conditions, abolition of prolyl hydroxylation results in HIF-1 stabilization, whereas the lack of asparaginyl hydroxylation allows the transcriptional activity. Additionally, the transcriptional activity may be modulated by phosphorylation or redox modification of HIF-1. Despite its name, HIF-1 is induced not only in response to reduced oxygen availability but also by other stimulants, such as nitric oxide, various growth factors, or direct inhibitors of prolyl and asparaginyl hydroxylases. Therefore, it seems to be a crucial transcription factor elicited by a wide range of stresses such as impaired oxygenation, inflammation, energy deprivation, or intensive proliferation. However, the mechanisms of normoxic activation, as well as of oxygen sensing, are not yet fully known. Further understanding of the processes that control HIF-1 activity will be crucial for the development of new diagnostic and therapeutic strategies.

8

Peroksydacja lipidow oraz wybrane antyoksydanty w watrobie szczurow po doustnej ekspozycji na chlorek niklu[II]

51%

Janicka K. , Cempel M.

Bromatologia i Chemia Toksykologiczna

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2001

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tom 34

|

nr 4

291-295

PL

Oznaczono peroksydację lipidów (poziom malonylodialdehydu-MDA) oraz niektóre antyoksydanty (glutation zredukowany-GSH, katalaza-CAT i oksygenaza hemowa-OH) w wątrobie szczurów, którym podawano w wodzie pitnej chlorek niklu(II) w stęż. 300 ppm Ni (180 dni) i 1200 ppm Ni (90 dni). Stwierdzono statystycznie istotne podwyższenie peroksydacji lipidów: przejściowe w przypadku stęż. 300 ppm (po 30 dniach) oraz stały wzrost w przypadku 1200 ppm. Nie wykazano istotnego wpływu badanego związku na poziom wybranych antyoksydantów.

EN

Male Wistar rats received nickel as nickel(II) chloride in drinking water at 300 and 1200 ppm for 180 and 90 days, respectively. The aim of this work was to examine the effect of that chemical on liver lipid peroxidation (in terms of malonyl dialdehyde) and some antioxidants (reduced glutathione-GSH, catalase-CAT, heme oxygenase-HO). A significant increase in lipid peroxidation was noted in the exposed rats. The rise in malonyl dialdehyde (ca. 50%) was temporary (30 days) for the 300 ppm Ni exposure and chronic (throughout the experiment) for 1200 ppm Ni. No significant changes were noted in the level of reduced glutathione, or catalase and heme oxygenase activity.