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Herbertsson, Helena
Publications (8 of 8) Show all publications
Svensson Holm, A.-C., Berg, C., Herbertsson, H., Söderström, M., Hammarström, S., Lindström, E. & Bengtsson, T. (2006). 5-Lipoxygenase activity is involved in platelet-induced fibroblast proliferation. Paper presented at Kardiovaskulära vårmötet, Linköping.
Open this publication in new window or tab >>5-Lipoxygenase activity is involved in platelet-induced fibroblast proliferation
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2006 (English)Conference paper, Published paper (Refereed)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-69447 (URN)
Conference
Kardiovaskulära vårmötet, Linköping
Available from: 2011-06-28 Created: 2011-06-28 Last updated: 2013-10-23
Svensson Holm, A.-C., Berg, C., Herbertsson, H., Söderström, M., Hammarström, S., Lindström, E. & Bengtsson, T. (2006). 5-Lipoxygenase activity is involved in platelet-induced fibroblast proliferation. Paper presented at XIV International Symposium on Atherosclerosis, Rom.
Open this publication in new window or tab >>5-Lipoxygenase activity is involved in platelet-induced fibroblast proliferation
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2006 (English)Conference paper, Published paper (Refereed)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-69442 (URN)
Conference
XIV International Symposium on Atherosclerosis, Rom
Available from: 2011-06-28 Created: 2011-06-28 Last updated: 2013-10-23
Berg, C., Hammarström, S., Herbertsson, H., Lindström, E., Svensson, A.-C., Söderström, M., . . . Bengtsson, T. (2006). Platelet-induced growth of human fibroblasts is associated with an increased expression of 5-lipoxygenase. Thrombosis and Haemostasis, 96(5), 652-659
Open this publication in new window or tab >>Platelet-induced growth of human fibroblasts is associated with an increased expression of 5-lipoxygenase
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2006 (English)In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 96, no 5, p. 652-659Article in journal (Refereed) Published
Abstract [en]

Proliferation of fibroblasts is vital for adequate wound healing but is probably also involved in different hyperproliferative disorders such as atherosclerosis and cancer. The regeneration of tissue usually starts with coagulation, involving release of mitogenic and inflammatory factors from activated platelets. This study focuses on the role of eicosanoids in the proliferative effects of platelets on human fibroblasts. We show that the phospholipase A2 inhibitor 7,7-dimethyl-5,8-eicosadienoic acid (DMDA), the combined cyclooxygenase (COX) and lipoxygenase (LOX) inhibitor 5,8,11,14-eicosatetraynoic acid (ETYA) and the LOX inhibitor 5,8,11-eicosatriynoic acid (ETI) block the platelet-induced proliferation of serum starved subconfluent human fibroblasts. Anti-proliferative effects were also obtained by specific inhibition of 5-LOX with 5,6-dehydro arachidonic acid (5,6-dAA), whereas the 12-LOX inhibitor cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC) did not affect the platelet-stimulated growth of fibroblasts. The expression of 5-LOX was analyzed by reverse-transcriptase-mediated PCR (RT-PCR), Western blotting and HPLC. 5-LOX message and protein was detected in fibroblasts but not in platelets. Incubation with platelets markedly increased, already after one hour, the expression of 5-LOX in the fibroblast culture. The increased 5-LOX activity was associated with an elevated level of the 5-LOX metabolite 5-hydroxyeicosatetraenoic acid (5-HETE) reaching its maximum after 1-2 hours of co-incubation of fibroblasts and platelets. The 5-HETE production was reduced by the inhibitors DMDA, ETYA and ETI. In conclusion, this study suggests that platelet-stimulated proliferation of fibroblasts is mediated by an increased 5-LOX activity, which supports recent findings indicating a crucial role for this enzyme in proliferative disorders such as atherosclerosis. © 2006 Schattauer GmbH, Stuttgart.

National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-36111 (URN)10.1160/TH06-02-0069 (DOI)000242168400016 ()29986 (Local ID)29986 (Archive number)29986 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
Kurahashi, Y., Herbertsson, H., Söderström, M., Rosenfeld, M. G. & Hammarström, S. (2000). A 12(S)-hydroxyeicosatetraenoic acid receptor interacts with steroid receptor coactivator-1. Proceedings of the National Academy of Sciences of the United States of America, 97(11), 5779-5783
Open this publication in new window or tab >>A 12(S)-hydroxyeicosatetraenoic acid receptor interacts with steroid receptor coactivator-1
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2000 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 97, no 11, p. 5779-5783Article in journal (Refereed) Published
Abstract [en]

Lewis lung carcinoma cells contain specific high-affinity binding sites for the eicosanoid 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid [12(S)-HETE]. These binding sites have a cytosolic/nuclear localization and contain the heat shock proteins hsp70 and hsp90 as components of a high molecular weight cytosolic binding complex. The ligand binding subunit of this complex is a protein with an apparent molecular mass of ÿ50 kDa as judged by gel permeation chromatography. In this report, we present data showing that the 50-kDa 12(S)-HETE binding protein interacts as a homodimer with steroid receptor coactivator-1 (SRC-1) in the presence of 12(S)-HETE. Two putative interaction domains were mapped. One of these (amino acids 701-781) was within the nuclear receptor interaction domain in SRC-1 required for binding of various steroid and thyroid hormone receptors. It contains the most C-terminal of the three copies of LXXLL motif present in the nuclear receptor interaction domain. The second interaction domain was present in the N-terminal part of SRC-1 (amino acids 1-221). This region has two LXXLL motifs, one does not bind and the other binds only weakly to steroid and thyroid hormone receptors. Glutathione S-transferase (GST) pulldown experiments and far Western analyses demonstrated that the N-terminal region of SRC-1 (amino acids 1-212) alone does not bind the 50-kDa 12(S)-HETE binding protein, whereas GST/?SRC-11-1138 ligand-dependently pulled down a protein of ÿ50 kDa in size. Our results suggest that the 50-kDa 12(S)-HETE binding protein is a receptor that may signal through interaction with a nuclear receptor coactivator protein.

Place, publisher, year, edition, pages
National Academy of Sciences, 2000
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25055 (URN)10.1073/pnas.97.11.5779 (DOI)000087318700022 ()10823935 (PubMedID)9483 (Local ID)9483 (Archive number)9483 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
Herbertsson, H., Kühme, T. & Hammarström, S. (2000). Subunits and cellular occurrence of the 12(S)-HETE binding complex. Advances in Experimental Medicine and Biology, 469, 253-258
Open this publication in new window or tab >>Subunits and cellular occurrence of the 12(S)-HETE binding complex
2000 (English)In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 469, p. 253-258Article in journal (Other academic) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25472 (URN)9918 (Local ID)9918 (Archive number)9918 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
Herbertsson, H., Kühme, T. & Hammarström, S. (1999). A 12(S)-HETE receptor in Lewis lung carcinoma cells.. Advances in Experimental Medicine and Biology, 447, 193-198
Open this publication in new window or tab >>A 12(S)-HETE receptor in Lewis lung carcinoma cells.
1999 (English)In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 447, p. 193-198Article in journal (Other academic) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25471 (URN)9917 (Local ID)9917 (Archive number)9917 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
Herbertsson, H., Kyhme, T. & Hammarström, S. (1999). The 650-kDA 12(S)-Hydroxyeicosatetraenoic acid binding complex: Occurrence in human platelets, identification of Hsp90 as a constituent, and binding properties of its 50-kDa subunit.. Archives of Biochemistry and Biophysics, 367, 33-38
Open this publication in new window or tab >>The 650-kDA 12(S)-Hydroxyeicosatetraenoic acid binding complex: Occurrence in human platelets, identification of Hsp90 as a constituent, and binding properties of its 50-kDa subunit.
1999 (English)In: Archives of Biochemistry and Biophysics, ISSN 0003-9861, E-ISSN 1096-0384, Vol. 367, p. 33-38Article in journal (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25059 (URN)9487 (Local ID)9487 (Archive number)9487 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
Herbertsson, H. (1998). Studies on a novel cytosolic/nuclear binding protein for the eicosanoid 12(S)-hydroxyeicosatetraenoic acid. (Doctoral dissertation). Linköping: Linköpings universitet
Open this publication in new window or tab >>Studies on a novel cytosolic/nuclear binding protein for the eicosanoid 12(S)-hydroxyeicosatetraenoic acid
1998 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Hydroxyeicosatetraenoic acids (HETEs) are lipoxygenase metabolites of arachidonic acid. HETEs were long considered to have few or no important biological function - a view that proved to be incorrect. These compounds have now been identified in many different types of cells, and they have been attributed several important actions, the molecular mechanisms of which are largely unclear. This thesis describes the discovery of a putative receptor for 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(S)-HETE).

Specific high-affinity binding sites for 12(S)-HETE were detected in the cytosol (52%) and the nuclei (18%) of cells of the Lewis lung carcinoma (LLC) line. Similar l2(S)-HETE binding sites were detected in the cytosol of several other kinds of cells and in human platelets. Gel permeation chromatography and density gradient centrifugation indicated an apparent molecular weight of about 650 kDa and a sedimentation coefficient of20.5 S for the binding sites in the cytosol ofLLC cells. Treatment with ATP caused the 650 kDa component to dissociate into subunits. The actuall2(S)-HETE binding subunit was subsequently shown to have a molecular weight of about 50 kDa.

The subcellular distribution of l2(S)-HETE binding sites in LLC cells was found to resemble the distribution of some nuclear receptors of the steroid hormone receptor superfamily. The untransformed glucocorticoid receptor has been reported to be located in cytosol in association with heat shock proteins 70 and 90, and Western blot analyses and immunoprecipitation revealed the same two proteins in the cytosolic 650 kDa l2(S)-HETE binding complex.

A possible relationship to the steroid hormone receptor superfamily was also suggested by the observation that the 50 kDa l2(S)-HETE binding protein interacted with steroid receptor coactivator-l (SRC-l), which is known to be recruited to the site of transcriptional activity by several nuclear receptors. The interaction with SRC-1 occurred only when l2(S)-HETE was bound to its 50 kDa binding protein.

In summary, the research presented in this thesis led to the discovery of a novel type of eicosanoid receptor. This binding site resembles the nuclear receptors for steroids and related compounds by virtue of its subcellular distribution, the inclusion of heat shock proteins in its binding complex, and its strictly ligand-dependent interaction with SRC-l.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 1998. p. 48
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 575
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25658 (URN)10034 (Local ID)91-7219-061-2 (ISBN)10034 (Archive number)10034 (OAI)
Public defence
1998-12-04, Berzeliussalen, Universitetssjukhuset, Linköping, 09:00 (Swedish)
Opponent
Note

Papers, included in the Ph.D. thesis, are not registered and included in the posts from 1999 and backwards.

Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-11-09Bibliographically approved
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