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Likus, W., Siemianowicz, K., Markowski, J., Wiaderkiewicz, J., Kostrzab-Zdebel, A., Jura-Szoltys, E., . . . Los, M. J. (2016). Bacterial Infections and Osteoclastogenesis Regulators in Men and Women with Cholesteatoma. Archivum Immunologiae et Therapiae Experimentalis, 64(3), 241-247
Open this publication in new window or tab >>Bacterial Infections and Osteoclastogenesis Regulators in Men and Women with Cholesteatoma
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2016 (English)In: Archivum Immunologiae et Therapiae Experimentalis, ISSN 0004-069X, E-ISSN 1661-4917, Vol. 64, no 3, p. 241-247Article, review/survey (Refereed) Published
Abstract [en]

One of the most distinct features of middle ear cholesteatoma is bone destruction. Aetiology of cholesteatoma is thought to be multifactorial. Endotoxins produced by bacteria are thought to initiate the inflammation process in the middle ear leading to cholesteatoma. There are physiological differences in bone metabolism between men and women. The aim of our study was the immunohistochemical evaluation of the contents of two key components of the OPG/RANK/RANKL triad-RANKL and OPG in cholesteatoma, to analyse if there are any differences between the sexes and to evaluate the bacteria species isolated from cholesteatoma just before surgical treatment and to evaluate their plausible influence on the expression of OPG and RANKL in cholesteatoma. Twenty-one adult patients with acquired cholesteatoma who underwent surgery were analysed. There were no statistically significant differences in the expression of both regulators of osteoclastogenesis between the sexes. In 38.1 % patients cholesteatoma was not infected, whereas in 61.9 % patients various bacterial infections or mycosis were found. The most frequently isolated species was Pseudomonas aeruginosa (14.29 % infections) followed by Staphylococcus aureus (9.52 % infections). There were no statistically significant differences in expression of both OPG and RANKL between uninfected and infected cholesteatomas.

Place, publisher, year, edition, pages
SPRINGER BASEL AG, 2016
Keywords
Cholesteatoma; Osteoprotegerin; RANKL; Bacterial infection; Sexes
National Category
Hematology
Identifiers
urn:nbn:se:liu:diva-129139 (URN)10.1007/s00005-015-0373-7 (DOI)000376060200005 ()26584851 (PubMedID)
Note

Funding Agencies|Medical University of Silesia in Katowice, Poland [KNW-1-096/P/2/0]

Available from: 2016-06-13 Created: 2016-06-13 Last updated: 2017-11-28
Gelmi, A., Cieslar-Pobuda, A., de Muinck, E., Los, M. J., Rafat, M. & Jager, E. (2016). Direct Mechanical Stimulation of Stem Cells: A Beating Electromechanically Active Scaffold for Cardiac Tissue Engineering. Advanced Healthcare Materials, 5(12), 1471-1480
Open this publication in new window or tab >>Direct Mechanical Stimulation of Stem Cells: A Beating Electromechanically Active Scaffold for Cardiac Tissue Engineering
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2016 (English)In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 5, no 12, p. 1471-1480Article in journal (Refereed) Published
Abstract [en]

The combination of stem cell therapy with a supportive scaffold is a promising approach to improving cardiac tissue engineering. Stem cell therapy can be used to repair nonfunctioning heart tissue and achieve myocardial regeneration, and scaffold materials can be utilized in order to successfully deliver and support stem cells in vivo. Current research describes passive scaffold materials; here an electroactive scaffold that provides electrical, mechanical, and topographical cues to induced human pluripotent stem cells (iPS) is presented. The poly(lactic-co-glycolic acid) fiber scaffold coated with conductive polymer polypyrrole (PPy) is capable of delivering direct electrical and mechanical stimulation to the iPS. The electroactive scaffolds demonstrate no cytotoxic effects on the iPS as well as an increased expression of cardiac markers for both stimulated and unstimulated protocols. This study demonstrates the first application of PPy as a supportive electroactive material for iPS and the first development of a fiber scaffold capable of dynamic mechanical actuation.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Inc., 2016
Keywords
actuators; conductive polymers; scaffolds; stem cells; tissue engineering
National Category
Biophysics
Identifiers
urn:nbn:se:liu:diva-130427 (URN)10.1002/adhm.201600307 (DOI)000379550400010 ()27126086 (PubMedID)
Note

Funding Agencies|Linkoping University, Integrative Regenerative Medicine (IGEN) Center; Swedish Research Council [VR-2014-3079]; COST-Action [MP1003]; Knut och Alice Wallenberg Commemorative Fund; GeCONiI [POIG.02.03.01-24-099/13]; European Research Agency

Available from: 2016-08-07 Created: 2016-08-05 Last updated: 2019-10-08Bibliographically approved
Magnusson, K., Appelqvist, H., Cieslar-Pobuda, A., Wigenius, J., Karlsson, T., Los, M. J., . . . Nilsson, P. (2015). Differential vital staining of normal fibroblasts and melanoma cells by an anionic conjugated polyelectrolyte. Cytometry Part A, 87(3), 262-272
Open this publication in new window or tab >>Differential vital staining of normal fibroblasts and melanoma cells by an anionic conjugated polyelectrolyte
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2015 (English)In: Cytometry Part A, ISSN 1552-4922, E-ISSN 1552-4930, Vol. 87, no 3, p. 262-272Article in journal (Refereed) Published
Abstract [en]

Molecular probes for imaging of live cells are of great interest for studying biological and pathological processes. The anionic luminescent conjugated polythiophene (LCP) polythiophene acetic acid (PTAA), has previously been used for vital staining of cultured fibroblasts as well as transformed cells with results indicating differential staining due to cell phenotype. Herein, we investigated the behavior of PTAA in two normal and five transformed cells lines. PTAA fluorescence in normal cells appeared in a peripheral punctated pattern whereas the probe was more concentrated in a one-sided perinuclear localization in the five transformed cell lines. In fibroblasts, PTAA fluorescence was initially associated with fibronectin and after 24 h partially localized to lysosomes. The uptake and intracellular target in malignant melanoma cells was more ambiguous and the intracellular target of PTAA in melanoma cells is still elusive. PTAA was well tolerated by both fibroblasts and melanoma cells, and microscopic analysis as well as viability assays showed no signs of negative influence on growth. Stained cells maintained their proliferation rate for at least 12 generations. Although the probe itself was nontoxic, photoinduced cellular toxicity was observed in both cell lines upon irradiation directly after staining. However, no cytotoxicity was detected when the cells were irradiated 24 h after staining, indicating that the photoinduced toxicity is dependent on the cellular location of the probe. Overall, these studies certified PTAA as a useful agent for vital staining of cells, and that PTAA can potentially be used to study cancer-related biological and pathological processes.

Place, publisher, year, edition, pages
Wiley: 12 months, 2015
Keywords
Conjugated polyelectrolyte; Fibroblast; Fluorescence; Luminescent conjugated polythiophene; Melanoma; Photoinduced toxicity
National Category
Structural Biology Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-115887 (URN)10.1002/cyto.a.22627 (DOI)000349984200009 ()25605326 (PubMedID)2-s2.0-84923259526 (Scopus ID)
Available from: 2015-03-23 Created: 2015-03-23 Last updated: 2018-09-14
Gelmi, A., Zhang, J., Cieslar-Pobuda, A., Ljunggren, M., Los, M., Rafat, M. & Jager, E. (2015). Electroactive polymer scaffolds for cardiac tissue engineering. In: Bar-Cohen (Ed.), Proc. SPIE 9430, Electroactive Polymer Actuators and Devices (EAPAD) 2015: . Paper presented at Electroactive Polymer Actuators and Devices (EAPAD) 2015 (pp. 94301T-1-94301T-7). SPIE - International Society for Optical Engineering, 9430
Open this publication in new window or tab >>Electroactive polymer scaffolds for cardiac tissue engineering
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2015 (English)In: Proc. SPIE 9430, Electroactive Polymer Actuators and Devices (EAPAD) 2015 / [ed] Bar-Cohen, SPIE - International Society for Optical Engineering, 2015, Vol. 9430, p. 94301T-1-94301T-7Conference paper, Published paper (Refereed)
Abstract [en]

By-pass surgery and heart transplantation are traditionally used to restore the heart’s functionality after a myocardial Infarction (MI or heart attack) that results in scar tissue formation and impaired cardiac function. However, both procedures are associated with serious post-surgical complications. Therefore, new strategies to help re-establish heart functionality are necessary. Tissue engineering and stem cell therapy are the promising approaches that are being explored for the treatment of MI. The stem cell niche is extremely important for the proliferation and differentiation of stem cells and tissue regeneration. For the introduction of stem cells into the host tissue an artificial carrier such as a scaffold is preferred as direct injection of stem cells has resulted in fast stem cell death. Such scaffold will provide the proper microenvironment that can be altered electronically to provide temporal stimulation to the cells. We have developed an electroactive polymer (EAP) scaffold for cardiac tissue engineering. The EAP scaffold mimics the extracellular matrix and provides a 3D microenvironment that can be easily tuned during fabrication, such as controllable fibre dimensions, alignment, and coating. In addition, the scaffold can provide electrical and electromechanical stimulation to the stem cells which are important external stimuli to stem cell differentiation. We tested the initial biocompatibility of these scaffolds using cardiac progenitor cells (CPCs), and continued onto more sensitive induced pluripotent stem cells (iPS). We present the fabrication and characterisation of these electroactive fibres as well as the response of increasingly sensitive cell types to the scaffolds.

Place, publisher, year, edition, pages
SPIE - International Society for Optical Engineering, 2015
Series
Proceedings of SPIE, ISSN 0277-786X ; 9430
National Category
Medical Materials
Identifiers
urn:nbn:se:liu:diva-118260 (URN)10.1117/12.2084165 (DOI)000355580900052 ()
Conference
Electroactive Polymer Actuators and Devices (EAPAD) 2015
Available from: 2015-05-22 Created: 2015-05-22 Last updated: 2018-10-11Bibliographically approved
Jangamreddy, J. R., Jain, M. V., Hallbeck, A.-L., Roberg, K., Lotfi, K. & Los, M. J. (2015). Glucose starvation-mediated inhibition of salinomycin induced autophagy amplifies cancer cell specific cell death. OncoTarget, 6(12), 10134-10145
Open this publication in new window or tab >>Glucose starvation-mediated inhibition of salinomycin induced autophagy amplifies cancer cell specific cell death
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2015 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 6, no 12, p. 10134-10145Article in journal (Refereed) Published
Abstract [en]

Salinomycin has been used as treatment for malignant tumors in a small number of humans, causing far less side effects than standard chemotherapy. Several studies show that Salinomycin targets cancer-initiating cells (cancer stem cells, or CSC) resistant to conventional therapies. Numerous studies show that Salinomycin not only reduces tumor volume, but also decreases tumor recurrence when used as an adjuvant to standard treatments. In this study we show that starvation triggered different stress responses in cancer cells and primary normal cells, which further improved the preferential targeting of cancer cells by Salinomycin. Our in vitro studies further demonstrate that the combined use of 2-Fluoro 2-deoxy D-glucose, or 2-deoxy D-glucose with Salinomycin is lethal in cancer cells while the use of Oxamate does not improve cell death-inducing properties of Salinomycin. Furthermore, we show that treatment of cancer cells with Salinomycin under starvation conditions not only increases the apoptotic caspase activity, but also diminishes the protective autophagy normally triggered by the treatment with Salinomycin alone. Thus, this study underlines the potential use of Salinomycin as a cancer treatment, possibly in combination with short-term starvation or starvation-mimicking pharmacologic intervention.

Place, publisher, year, edition, pages
IMPACT JOURNALS LLC, 2015
Keywords
Glucose starvation, 2DG, 2FDG, Normoxia and Hypoxia, Differential Stress Response, autophagy, Akt, Tricirabine, Salinomycin
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-113707 (URN)000358874600039 ()
Available from: 2015-01-29 Created: 2015-01-29 Last updated: 2018-01-11Bibliographically approved
Reddy Jangamreddy, J., Panigrahi, S. & Los, M. J. (2015). Monitoring of autophagy is complicated: Salinomycin as an example. Biochimica et Biophysica Acta. Molecular Cell Research, 1853(3), 604-610
Open this publication in new window or tab >>Monitoring of autophagy is complicated: Salinomycin as an example
2015 (English)In: Biochimica et Biophysica Acta. Molecular Cell Research, ISSN 0167-4889, E-ISSN 1879-2596, ISSN 0167-4889, Vol. 1853, no 3, p. 604-610Article in journal (Refereed) Published
Abstract [en]

Monitoring of autophagy is challenging because of its multiple steps and lack of single befitting technique for a complete mechanistic understanding, which makes the task complicated. Here, we evaluate the functionality of autophagy triggered by salinomycin (anti-cancer stem cell agent) using flow cytometry and advanced microscopy. We show that salinomycin does induce functional autophagy at lower concentrations and such a dose is cell type-dependent. For example, PC3 cells show active autophagic flux at 10μM concentration of salinomycin while murine embryonic fibroblasts already show an inhibition of flux at such doses. A higher concentration of salinomycin (i.e. 30μM) inhibits autophagic flux in both cell types. The data confirms our previous findings that salinomycin is an inducer of autophagy, whereas autophagic flux inhibition is a secondary response.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Autophagic flux; GFP-LC3; Salinomycin; Vacuolization; mTandem GFP-RFP LC3; p62/SQSTRM1
National Category
Basic Medicine Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-113565 (URN)10.1016/j.bbamcr.2014.12.022 (DOI)000349878500007 ()25541282 (PubMedID)
Available from: 2015-01-23 Created: 2015-01-23 Last updated: 2018-01-11Bibliographically approved
Vilas Jain, M., Jangamreddy, J., Grabarek, J., Schweizer, F., Klonisch, T., Cieslar-Pobuda, A. & Los, M. J. (2015). Nuclear localized Akt enhances breast cancer stem-like cells through counter-regulation of p21(Waf1/Cip1) and p27(kip1). Cell Cycle, 14(13), 2109-2120
Open this publication in new window or tab >>Nuclear localized Akt enhances breast cancer stem-like cells through counter-regulation of p21(Waf1/Cip1) and p27(kip1)
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2015 (English)In: Cell Cycle, ISSN 1538-4101, E-ISSN 1551-4005, Vol. 14, no 13, p. 2109-2120Article in journal (Refereed) Published
Abstract [en]

Cancer stem-like cells (CSCs) are a rare subpopulation of cancer cells capable of propagating the disease and causing cancer recurrence. In this study, we found that the cellular localization of PKB/Akt kinase affects the maintenance of CSCs. When Akt tagged with nuclear localization signal (Akt-NLS) was overexpressed in SKBR3 and MDA-MB468 cells, these cells showed a 10-15% increase in the number of cells with CSCs enhanced ALDH activity and demonstrated a CD44(+High)/CD24(-Low) phenotype. This effect was completely reversed in the presence of Akt-specific inhibitor, triciribine. Furthermore, cells overexpressing Akt or Akt-NLS were less likely to be in G0/G1 phase of the cell cycle by inactivating p21(Waf1/Cip1) and exhibited increased clonogenicity and proliferation as assayed by colony-forming assay (mammosphere formation). Thus, our data emphasize the importance the intracellular localization of Akt has on stemness in human breast cancer cells. It also indicates a new robust way for improving the enrichment and culture of CSCs for experimental purposes. Hence, it allows for the development of simpler protocols to study stemness, clonogenic potency, and screening of new chemotherapeutic agents that preferentially target cancer stem cells. Summary: The presented data, (i) shows new, stemness-promoting role of nuclear Akt/PKB kinase, (ii) it underlines the effects of nuclear Akt on cell cycle regulation, and finally (iii) it suggests new ways to study cancer stem-like cells.

Place, publisher, year, edition, pages
Taylor and Francis: STM, Behavioural Science and Public Health Titles, 2015
Keywords
Akt-NLS; cancer stem-like cells; mTOR; PI3K; stemness
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-120274 (URN)10.1080/15384101.2015.1041692 (DOI)000356959800021 ()26030190 (PubMedID)
Note

Funding Agencies|Linkoping University; Integrative Regenerative Medicine Center (IGEN); VR-NanoVision [K2012-99X-22325-01-5]; Cancerfonden [2013/391]; Canadian Breast Cancer Foundation (CBCF); Natural Sciences and Engineering Research Council of Canada (NSERC); [BK/265/RAU1/2014/t.10]

Available from: 2015-07-24 Created: 2015-07-24 Last updated: 2018-01-11
Rezaei Moghadam, A., Tutunchi, S., Namvaran-Abbas-Abad, A., Yazdi, M., Bonyadi, F., Mohajeri, D., . . . Ghavami, S. (2015). Pre-administration of turmeric prevents methotrexate-induced liver toxicity and oxidative stress. BMC Complementary and Alternative Medicine, 15(246)
Open this publication in new window or tab >>Pre-administration of turmeric prevents methotrexate-induced liver toxicity and oxidative stress
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2015 (English)In: BMC Complementary and Alternative Medicine, ISSN 1472-6882, E-ISSN 1472-6882, Vol. 15, no 246Article in journal (Refereed) Published
Abstract [en]

Background: Methotrexate (MTX) is an antimetabolite broadly used in treatment of cancer and autoimmune diseases. MTX-induced hepatotoxicity limits its application. We investigated hepatoprotective effects of turmeric in MTX-induced liver toxicity. Methods: All experiments were performed on male Wistar albino rats that were randomly divided into six groups. Group one received saline orally for 30 days (control group), groups two and three received turmeric extract (100, 200 mg/kg respectively) orally for 30 days, group four received single dose, of MTX IP at day 30, groups five and six received turmeric extract 100 and 200 mg/kg orally respectively for 30 days and single dose of methoterxate IP (20 mg/kg) at day 30. Four days after MTX injection animals were sacrificed and evaluated. Blood ALT and AST (indicators of hepatocyte injury), ALP and bilirubin (markers of biliary function), albumin (reflect liver synthetic function) as well as the plasma TAS concentration (antioxidant defenses) were determined. The cellular antioxidant defense activities were examined in liver tissue samples using SOD, CAT, and GSH-Px for the oxidative stress, and MDA for lipid peroxidation. In addition, liver damage was evaluated histopathologically. Results: MTX significantly induced liver damage (P less than 0.05) and decreased its antioxidant capacity, while turmeric was hepatoprotective. Liver tissue microscopic evaluation showed that MTX treatment induced severe centrilobular and periportal degeneration, hyperemia of portal vein, increased artery inflammatory cells infiltration and necrosis, while all of histopathological changes were attenuated by turmeric (200 mg/kg). Conclusion: Turmeric extract can successfully attenuate MTX-hepatotoxicity. The effect is partly mediated through extracts antinflammatory activity.

Place, publisher, year, edition, pages
BioMed Central, 2015
Keywords
Lipid peroxides; Total antioxidant status; Antioxidant enzymes; Serum liver biomarkers; Hepatocellular injury; Cell death
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-120647 (URN)10.1186/s12906-015-0773-6 (DOI)000358201500004 ()26199067 (PubMedID)
Note

Funding Agencies|University of Manitoba start-up fund; Linkoping University; IGEN; Cancerfonden [2013/391]; VR-NanoVision [K2012-99X-22325-01-5]

Available from: 2015-08-20 Created: 2015-08-20 Last updated: 2017-12-04
Shakeri, R., Hosseinkhani, S., Los, M. J., Davoodi, J., Jain, M. V., Cieslar-Pobuda, A., . . . Kaboudanian Ardestani, S. (2015). Role of the salt bridge between glutamate 546 and arginine 907 in preservation of autoinhibited form of Apaf-1. International Journal of Biological Macromolecules, 81, 370-374
Open this publication in new window or tab >>Role of the salt bridge between glutamate 546 and arginine 907 in preservation of autoinhibited form of Apaf-1
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2015 (English)In: International Journal of Biological Macromolecules, ISSN 0141-8130, E-ISSN 1879-0003, Vol. 81, p. 370-374Article in journal (Refereed) Published
Abstract [en]

Apaf-1, the key element of apoptotic mitochondrial pathway, normally exists in an auto-inhibited form inside the cytosol. WRD-domain of Apaf-1 has a critical role in the preservation of auto-inhibited form; however the underlying mechanism is unclear. It seems the salt bridges between WRD and NOD domains are involved in maintaining the inactive conformation of Apaf-1. At the present study, we have investigated the effect of E546-R907 salt bridge on the maintenance of auto-inhibited form of human Apaf-1. E546 is mutated to glutamine (Q) and arginine (R). Over-expression of wild type Apaf-1 and its E546Q and E546R variants in HEK293T cells does not induce apoptosis unlike - HL-60 cancer cell line. In vitro apoptosome formation assay showed that all variants are cytochrome c and dATP dependent to form apoptosome and activate endogenous procaspase-9 in Apaf-1-knockout MEF cell line. These results suggest that E546 is not a critical residue for preservation of auto-inhibited Apaf-1. Furthermore, the behavior of Apaf-1 variants for in vitro apoptosome formation in HEK293T cell is similar to exogenous wild type Apaf-1. Wild type and its variants can form apoptosome in HEK293T cell with different procaspase-3 processing pattern in the presence and absence of exogenous cytochrome c and dATP. (C) 2015 Elsevier B.V. All rights reserved.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2015
Keywords
Apaf-1; Apoptosome; Caspase-9
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:liu:diva-124522 (URN)10.1016/j.ijbiomac.2015.08.027 (DOI)000367408300045 ()26277751 (PubMedID)
Note

Funding Agencies|Research Council of University of Tehran; Tarbiat Modares University; Linkoping University; Integrative Regenerative Medicine Center (IGEN); Cancerfonden [2013/391]; VR-NanoVision [K2012-99X-22325-01-5]

Available from: 2016-02-02 Created: 2016-02-01 Last updated: 2017-11-30
Ghavami, S., Sharma, P., Yeganeh, B., Ojo, O. O., Jha, A., Mutawe, M. M., . . . Halayko, A. J. (2014). Airway mesenchymal cell death by mevalonate cascade inhibition: integration of autophagy, unfolded protein response and apoptosis focusing on Bcl2 family proteins. Biochimica et Biophysica Acta. Molecular Cell Research, 1843(7), 1259-1271
Open this publication in new window or tab >>Airway mesenchymal cell death by mevalonate cascade inhibition: integration of autophagy, unfolded protein response and apoptosis focusing on Bcl2 family proteins
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2014 (English)In: Biochimica et Biophysica Acta. Molecular Cell Research, ISSN 0167-4889, E-ISSN 1879-2596, Vol. 1843, no 7, p. 1259-1271Article in journal (Refereed) Published
Abstract [en]

HMG-CoA reductase, the proximal rate-limiting enzyme in the mevalonate pathway, is inhibited by statins. Beyond their cholesterol lowering impact, statins have pleiotropic effects and their use is linked to improved lung health. We have shown that mevalonate cascade inhibition induces apoptosis and autophagy in cultured human airway mesenchymal cells. Here, we show that simvastatin also induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in these cells. We tested whether coordination of ER stress, autophagy and apoptosis determines survival or demise of human lung mesenchymal cells exposed to statin. We observed that simvastatin exposure activates UPR (activated transcription factor 4, activated transcription factor 6 and IRE1 alpha) and caspase-4 in primary human airway fibroblasts and smooth muscle cells. Exogenous mevalonate inhibited apoptosis, autophagy and UPR, but exogenous cholesterol was without impact, indicating that sterol intermediates are involved with mechanisms mediating statin effects. Caspase-4 inhibition decreased simvastatin-induced apoptosis, whereas inhibition of autophagy by ATG7 or ATG3 knockdown significantly increased cell death. In BAX(-/-)/BAIC(-/) murine embryonic fibroblasts, simvastatin-triggered apoptotic and UPR events were abrogated, but autophagy flux was increased leading to cell death via necrosis. Our data indicate that mevalonate cascade inhibition, likely associated with depletion of sterol intermediates, can lead to cell death via coordinated apoptosis, autophagy, and ER stress. The interplay between these pathways appears to be principally regulated by autophagy and Bcl-2-family pro-apoptotic proteins. These findings uncover multiple mechanisms of action of statins that could contribute to refining the use of such agent in treatment of lung disease.

Place, publisher, year, edition, pages
Elsevier, 2014
Keywords
Statin, Cell deat, Endoplasmic reticulum stress, Fibroblast
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-108152 (URN)10.1016/j.bbamcr.2014.03.006 (DOI)000336713600003 ()24637330 (PubMedID)
Available from: 2014-06-26 Created: 2014-06-26 Last updated: 2017-12-05Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-9518-1411

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