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Alicia Torriglia - One of the best experts on this subject based on the ideXlab platform.
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the hidden side of serpinb1 Leukocyte Elastase Inhibitor
Seminars in Cell & Developmental Biology, 2017Co-Authors: Alicia Torriglia, Imene Jaadane, Elisabeth MartinAbstract:SERPINB1, also called Leukocyte Elastase Inhibitor (LEI) is a member of the clade B of SERPINS. It is an intracellular protein and acts primarily to protect the cell from proteases released into the cytoplasm during stress. Its role in inflammation is clear due to its involvement in the resolution of chronic inflammatory lung and bowel diseases. LEI/SERPINB1 intrinsically possesses two enzymatic activities: an antiprotease activity dependent on its reactive site loop, which is analogous to the other proteins of the family and an endonuclease activity which is unveiled by the cleavage of the reactive site loop. The conformational change induced by this cleavage also unveils a bipartite nuclear localization signal allowing the protein to translocate to the nucleus. Recent data indicate that it has also a role in cell migration suggesting that it could be involved in diverse processes like wound healing and malignant metastases.
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Increase in the expression of Leukocyte Elastase Inhibitor during wound healing in corneal endothelial cells
Cell and Tissue Research, 2015Co-Authors: Cristian Justet, Alicia Torriglia, Frances Evans, Silvia ChiffletAbstract:Tissue injury triggers a complex network of cellular and molecular responses. Although cell migration and proliferation are the most conspicuous, several other responses, such as apoptosis and increased protease activity, are necessary for a proper restitution of the tissue. In this work, we study the Leukocyte Elastase Inhibitor (LEI) expression during wound healing of bovine corneal endothelial monolayers in culture. LEI is a multifunctional protein with anti-protease and anti-apoptotic activity. When properly cleaved, it is transformed into L-DNase II, a pro-apoptotic enzyme and translocated to the nucleus. We found that early after injury LEI increases its protein and mRNA expressions, without nuclear translocation and returns to basal levels immediately after wound closure. This increase is blocked by N-acetylcysteine, suggesting that production of reactive oxygen species immediately after wounding is involved in the LEI increase. Another finding of this work is that there is an acidification of the cells at the wound border which, in contrast to other cell types, does not determine nuclear translocation of the protein. Taken together, the results of this work suggest that the function of LEI during wound healing is related to its activity as a protease Inhibitor and/or to its anti-apoptotic activity.
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interaction of Leukocyte Elastase Inhibitor l dnase ii with bcl 2 and bax
Biochimica et Biophysica Acta, 2014Co-Authors: Imene Jaadane, Atf Nagbou, Francine Beharcohen, Alicia TorrigliaAbstract:Abstract Leukocyte Elastase Inhibitor (LEI, also called serpin B1) is a protein involved in apoptosis among other physiological processes. We have previously shown that upon cleavage by its cognate protease, LEI is transformed into L-DNase II, a protein with a pro-apoptotic activity. The caspase independent apoptotic pathway, in which L-DNase II is the final effector, interacts with other pro-apoptotic molecules like Poly-ADP-Ribose polymerase (PARP) or Apoptosis Inducing Factor (AIF). The screening of LEI/L-DNase II interactions showed a possible interaction with several members of the BCL-2 family of proteins which are known to have a central role in the regulation of caspase dependent cell death. In this study, we investigated the regulation of LEI/L-DNase II pathway by two members of this family of proteins: BAX and BCL-2, which have opposite effects on cell survival. We show that, in both BHK and HeLa cells, LEI/L-DNase II can interact with BCL-2 and BAX in apoptotic and non-apoptotic conditions. These proteins which are usually thought to be anti-apoptotic and pro-apoptotic respectively, both inhibit the L-DNase II pro-apoptotic activity. These results give further insight in the regulation of caspase independent pathways and highlight the involvement of the intracellular environment of a given protein in the determinism of its function. They also add a link between caspase-dependent and independent pathways of apoptosis.
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apoptosis inducing factor aif and Leukocyte Elastase Inhibitor l dnase ii lei ldnaseii can interact to conduct caspase independent cell death
Apoptosis, 2013Co-Authors: Chloé Leprêtre, Alicia Torriglia, Guergana Tchakarska, Hounayda Blibech, Cecile LebonAbstract:Programmed cell death is an important factor in tissue homeostasis. Lot of work has been performed to characterize the caspase-dependent cell death. Caspase-independent cell death, although important in many physiological situations, is less investigated. In this work we show that two caspase-independent effectors of cell death, namely apoptosis-inducing factor and Leukocyte Elastase Inhibitor derived DNase II interact and can cooperate to induce cell death. These results contribute to the knowledge of molecular pathways of cell death, an important issue in the development of new therapeutic strategies for the treatment of cancer or neurodegenerative diseases.
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Leukocyte Elastase Inhibitor a new regulator of parp 1
Annals of the New York Academy of Sciences, 2009Co-Authors: Chloé Leprêtre, Alicia Torriglia, Giuseppina Sidoli, Ivana A ScovassiAbstract:Poly(ADP-ribose) polymerase-1 (PARP-1) uses NAD(+) as a substrate to form ADP-ribose. During apoptosis, caspases cleave PARP-1 to avoid excessive NAD consumption. Because PARP-1 is a key regulator of the activity of DNases involved in caspase-dependent apoptosis, its cleavage is required to promote DNA degradation. To explore the situation in caspase-independent cell death, we investigated the effect of PARP-1 on the acid endonuclease Leukocyte Elastase Inhibitor (LEI)-derived DNase II (L-DNase II). We found for the first time an association between PARP-1 and LEI/L-DNase II. Unexpectedly, we observed that LEI influenced the automodification of PARP-1.
Chloé Leprêtre - One of the best experts on this subject based on the ideXlab platform.
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apoptosis inducing factor aif and Leukocyte Elastase Inhibitor l dnase ii lei ldnaseii can interact to conduct caspase independent cell death
Apoptosis, 2013Co-Authors: Chloé Leprêtre, Alicia Torriglia, Guergana Tchakarska, Hounayda Blibech, Cecile LebonAbstract:Programmed cell death is an important factor in tissue homeostasis. Lot of work has been performed to characterize the caspase-dependent cell death. Caspase-independent cell death, although important in many physiological situations, is less investigated. In this work we show that two caspase-independent effectors of cell death, namely apoptosis-inducing factor and Leukocyte Elastase Inhibitor derived DNase II interact and can cooperate to induce cell death. These results contribute to the knowledge of molecular pathways of cell death, an important issue in the development of new therapeutic strategies for the treatment of cancer or neurodegenerative diseases.
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Leukocyte Elastase Inhibitor a new regulator of parp 1
Annals of the New York Academy of Sciences, 2009Co-Authors: Chloé Leprêtre, Alicia Torriglia, Giuseppina Sidoli, Ivana A ScovassiAbstract:Poly(ADP-ribose) polymerase-1 (PARP-1) uses NAD(+) as a substrate to form ADP-ribose. During apoptosis, caspases cleave PARP-1 to avoid excessive NAD consumption. Because PARP-1 is a key regulator of the activity of DNases involved in caspase-dependent apoptosis, its cleavage is required to promote DNA degradation. To explore the situation in caspase-independent cell death, we investigated the effect of PARP-1 on the acid endonuclease Leukocyte Elastase Inhibitor (LEI)-derived DNase II (L-DNase II). We found for the first time an association between PARP-1 and LEI/L-DNase II. Unexpectedly, we observed that LEI influenced the automodification of PARP-1.
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Leukocyte Elastase Inhibitor a new regulator of parp 1
Annals of the New York Academy of Sciences, 2009Co-Authors: Chloé Leprêtre, Alicia Torriglia, Giuseppina Sidoli, Ivana A ScovassiAbstract:as a substrate to for m A DP-ribose .During apoptosis , caspases clea ve P A RP-1 to avoid ex cessiv e N A D consumption. B e-cause P ARP-1 is a k ey reg ulator o f the activity of DNases in vo lv ed in caspase-de pendentapoptosis ,its clea va ge is required to promote D N A de g radation. T o ex plore the situationin caspase-inde pendent cell death, w e in vestigated the effect o f P ARP-1 o n the acid en-don u clease leuk ocyte Elastase Inhibitor (LEI)Ðderiv ed DNase II (L-DNase II). W e foundfor the Þr st time an association b etw een P A RP-1 and LEI/L-DNase II. Une x pectedl y,w eobser ved that LEI insuenced the a utomodiÞcation of P A RP-1.Key words: apoptosis; L-DNase II; LEI; P A RP-1; p ol y(ADP-ribosylation)
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regulation of poly adp ribose polymerase 1 functions by Leukocyte Elastase Inhibitor lei derived dnase ii during caspase independent apoptosis
The International Journal of Biochemistry & Cell Biology, 2009Co-Authors: Chloé Leprêtre, Alicia Torriglia, A I Scovassi, G M ShahAbstract:Abstract Poly(ADP-ribose) polymerase-1 (PARP-1) is an important regulator of apoptosis. Its over-activation at the onset of apoptosis can inhibit the action of apoptotic endonucleases like caspase-activated DNase and DNAS1L3. Therefore, controlled PARP-1 proteolysis during caspase-dependent apoptosis is considered essential to promote DNA degradation. Yet, little is known about the interplay of PARP-1 and endonucleases that operate during caspase-independent cell death. Here we show that in the long-term cultured HeLa cells which undergo caspase-independent death, PARP-1 co-immunoprecipitates with Leukocyte Elastase Inhibitor-derived DNase II (L-DNase II), an acid DNase implicated in this death pathway and activated by serine proteases. Our results indicate that, despite having putative poly(ADP-ribose)-acceptor sites, LEI/L-DNase II is neither significantly poly(ADP-ribosyl)ated nor inhibited by PARP-1 during caspase-independent apoptosis. Unexpectedly, caspase-independent apoptosis induced by hexa-methylene amiloride, LEI/L-DNase II can activate PARP-1 and promote its auto-poly(ADP-ribosyl)ation, thus inhibiting PARP-1 activity. Moreover, overexpression of LEI blocks the pro-survival effect of PARP-1 in this model of cell death. Our results provide the original evidence for a new mechanism of PARP-1 activity regulation in the caspase-independent death pathway involving LEI/L-DNase II.
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Leukocyte Elastase Inhibitor the precursor of l dnase ii inhibits apoptosis by interfering with caspase 8 activation
Biochimica et Biophysica Acta, 2008Co-Authors: Laura Padronbarthe, Chloé Leprêtre, Jacqueline Courta, Atf NagbouAbstract:Abstract LEI (Leukocyte Elastase Inhibitor), the precursor of the pro-apoptotic molecule L-DNase II, belongs to the ovalbumin subgroup of serpins. Several serpins can inhibit apoptosis: the viral serpin Crm A inhibits Fas or TNFα-induced apoptosis, and overexpression of PAI-2 or PI-9 protects cells from TNFα or granzyme B induced apoptosis. We have previously shown that LEI overexpression protects cells from etoposide-induced apoptosis. The molecular reason of this anti-apoptotic activity is now investigated. We show that, in BHK-21 and HeLa cells, LEI anti-protease activity is essential for its anti-apoptotic effect. The protease inhibited is cathepsin D, released from the lysosome during etoposide treatment. Cathepsin D enhances caspase activity in the cell by cleaving procaspase-8 and LEI overexpression slows down this cleavage, protecting cells from apoptosis. This let us presume that high expression of LEI in tumor cells may reduce the efficiency of etoposide as a chemotherapeutic agent.
Atf Nagbou - One of the best experts on this subject based on the ideXlab platform.
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interaction of Leukocyte Elastase Inhibitor l dnase ii with bcl 2 and bax
Biochimica et Biophysica Acta, 2014Co-Authors: Imene Jaadane, Atf Nagbou, Francine Beharcohen, Alicia TorrigliaAbstract:Abstract Leukocyte Elastase Inhibitor (LEI, also called serpin B1) is a protein involved in apoptosis among other physiological processes. We have previously shown that upon cleavage by its cognate protease, LEI is transformed into L-DNase II, a protein with a pro-apoptotic activity. The caspase independent apoptotic pathway, in which L-DNase II is the final effector, interacts with other pro-apoptotic molecules like Poly-ADP-Ribose polymerase (PARP) or Apoptosis Inducing Factor (AIF). The screening of LEI/L-DNase II interactions showed a possible interaction with several members of the BCL-2 family of proteins which are known to have a central role in the regulation of caspase dependent cell death. In this study, we investigated the regulation of LEI/L-DNase II pathway by two members of this family of proteins: BAX and BCL-2, which have opposite effects on cell survival. We show that, in both BHK and HeLa cells, LEI/L-DNase II can interact with BCL-2 and BAX in apoptotic and non-apoptotic conditions. These proteins which are usually thought to be anti-apoptotic and pro-apoptotic respectively, both inhibit the L-DNase II pro-apoptotic activity. These results give further insight in the regulation of caspase independent pathways and highlight the involvement of the intracellular environment of a given protein in the determinism of its function. They also add a link between caspase-dependent and independent pathways of apoptosis.
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Leukocyte Elastase Inhibitor the precursor of l dnase ii inhibits apoptosis by interfering with caspase 8 activation
Biochimica et Biophysica Acta, 2008Co-Authors: Laura Padronbarthe, Chloé Leprêtre, Jacqueline Courta, Atf NagbouAbstract:Abstract LEI (Leukocyte Elastase Inhibitor), the precursor of the pro-apoptotic molecule L-DNase II, belongs to the ovalbumin subgroup of serpins. Several serpins can inhibit apoptosis: the viral serpin Crm A inhibits Fas or TNFα-induced apoptosis, and overexpression of PAI-2 or PI-9 protects cells from TNFα or granzyme B induced apoptosis. We have previously shown that LEI overexpression protects cells from etoposide-induced apoptosis. The molecular reason of this anti-apoptotic activity is now investigated. We show that, in BHK-21 and HeLa cells, LEI anti-protease activity is essential for its anti-apoptotic effect. The protease inhibited is cathepsin D, released from the lysosome during etoposide treatment. Cathepsin D enhances caspase activity in the cell by cleaving procaspase-8 and LEI overexpression slows down this cleavage, protecting cells from apoptosis. This let us presume that high expression of LEI in tumor cells may reduce the efficiency of etoposide as a chemotherapeutic agent.
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Leukocyte Elastase Inhibitor the precursor of l dnase ii inhibits apoptosis by interfering with caspase 8 activation
Biochimica et Biophysica Acta, 2008Co-Authors: Laura Padronbarthe, Chloé Leprêtre, Jacqueline Courta, Atf NagbouAbstract:article i nfo LEI (Leukocyte Elastase Inhibitor), the precursor of the pro-apoptotic molecule L-DNase II, belongs to the ovalbumin subgroup of serpins. Several serpins can inhibit apoptosis: the viral serpin Crm A inhibits Fas or TNFα-induced apoptosis, and overexpression of PAI-2 or PI-9 protects cells from TNFα or granzyme B induced apoptosis. We have previously shown that LEI overexpression protects cells from etoposide-induced apoptosis. The molecular reason of this anti-apoptotic activity is now investigated. We show that, in BHK-21 and HeLa cells, LEI anti-protease activity is essential for its anti-apoptotic effect. The protease inhibited is cathepsin D, released from the lysosome during etoposide treatment. Cathepsin D enhances caspase activity in the cell by cleaving procaspase-8 and LEI overexpression slows down this cleavage, protecting cells from apoptosis. This let us presume that high expression of LEI in tumor cells may reduce the efficiency of etoposide as a chemotherapeutic agent.
Imene Jaadane - One of the best experts on this subject based on the ideXlab platform.
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the hidden side of serpinb1 Leukocyte Elastase Inhibitor
Seminars in Cell & Developmental Biology, 2017Co-Authors: Alicia Torriglia, Imene Jaadane, Elisabeth MartinAbstract:SERPINB1, also called Leukocyte Elastase Inhibitor (LEI) is a member of the clade B of SERPINS. It is an intracellular protein and acts primarily to protect the cell from proteases released into the cytoplasm during stress. Its role in inflammation is clear due to its involvement in the resolution of chronic inflammatory lung and bowel diseases. LEI/SERPINB1 intrinsically possesses two enzymatic activities: an antiprotease activity dependent on its reactive site loop, which is analogous to the other proteins of the family and an endonuclease activity which is unveiled by the cleavage of the reactive site loop. The conformational change induced by this cleavage also unveils a bipartite nuclear localization signal allowing the protein to translocate to the nucleus. Recent data indicate that it has also a role in cell migration suggesting that it could be involved in diverse processes like wound healing and malignant metastases.
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interaction of Leukocyte Elastase Inhibitor l dnase ii with bcl 2 and bax
Biochimica et Biophysica Acta, 2014Co-Authors: Imene Jaadane, Atf Nagbou, Francine Beharcohen, Alicia TorrigliaAbstract:Abstract Leukocyte Elastase Inhibitor (LEI, also called serpin B1) is a protein involved in apoptosis among other physiological processes. We have previously shown that upon cleavage by its cognate protease, LEI is transformed into L-DNase II, a protein with a pro-apoptotic activity. The caspase independent apoptotic pathway, in which L-DNase II is the final effector, interacts with other pro-apoptotic molecules like Poly-ADP-Ribose polymerase (PARP) or Apoptosis Inducing Factor (AIF). The screening of LEI/L-DNase II interactions showed a possible interaction with several members of the BCL-2 family of proteins which are known to have a central role in the regulation of caspase dependent cell death. In this study, we investigated the regulation of LEI/L-DNase II pathway by two members of this family of proteins: BAX and BCL-2, which have opposite effects on cell survival. We show that, in both BHK and HeLa cells, LEI/L-DNase II can interact with BCL-2 and BAX in apoptotic and non-apoptotic conditions. These proteins which are usually thought to be anti-apoptotic and pro-apoptotic respectively, both inhibit the L-DNase II pro-apoptotic activity. These results give further insight in the regulation of caspase independent pathways and highlight the involvement of the intracellular environment of a given protein in the determinism of its function. They also add a link between caspase-dependent and independent pathways of apoptosis.
Ke Won Kang - One of the best experts on this subject based on the ideXlab platform.
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isolation and characterization of guamerin a new human Leukocyte Elastase Inhibitor from hirudo nipponia
Journal of Biological Chemistry, 1995Co-Authors: Hyo Il Jung, Kwonsoo Ha, Ke Won KangAbstract:Abstract A new human Leukocyte Elastase Inhibitor was extracted and purified from a Korean native leech Hirudo nipponia. The Inhibitor, called guamerin, has a molecular weight of 6,110 and shows inhibition constant (K) of 8.1 10M. It is stable at a wide range of pH from 1 to 11 and heat-stable up to 90°C. The complete amino acid sequence of guamerin reveals a cysteine-rich polypeptide of 57 amino acid residues that shows no similarity to any known Elastase Inhibitors but has 51% sequence homology with hirustasin. Guamerin has identical spacing of 10 cysteine residues as antistasin-type serine proteinase Inhibitors, but the P1 reactive site residue is Met instead of Arg. The neighboring sequence of the reactive site consists primarily of hydrophobic amino acid residues. Based on examinations of the target proteinases and the reactive site specificity, guamerin is a new low molecular weight protein that inhibits Elastases.
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isolation and characterization of guamerin a new human Leukocyte Elastase Inhibitor from hirudo nipponia
Journal of Biological Chemistry, 1995Co-Authors: Hyo Il Jung, Seung Il Kim, Cheol O Joe, Ke Won KangAbstract:A new human Leukocyte Elastase Inhibitor was extracted and purified from a Korean native leech Hirudo nipponia. The Inhibitor, called guamerin, has a molecular weight of 6,110 and shows inhibition constant (Ki) of 8.1 x 10(-14) M. It is stable at a wide range of pH from 1 to 11 and heat-stable up to 90 degrees C. The complete amino acid sequence of guamerin reveals a cysteine-rich polypeptide of 57 amino acid residues that shows no similarity to any known Elastase Inhibitors but has 51% sequence homology with hirustasin. Guamerin has identical spacing of 10 cysteine residues as antistasin-type serine proteinase Inhibitors, but the P1 reactive site residue is Met36 instead of Arg. The neighboring sequence of the reactive site consists primarily of hydrophobic amino acid residues. Based on examinations of the target proteinases and the reactive site specificity, guamerin is a new low molecular weight protein that inhibits Elastases.