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Wäster, P., Eriksson, I., Vainikka, L., Rosdahl, I. & Öllinger, K. (2016). Extracellular vesicles are transferred from melanocytes to keratinocytes after UVA irradiation. Scientific Reports, 6(27890)
Open this publication in new window or tab >>Extracellular vesicles are transferred from melanocytes to keratinocytes after UVA irradiation
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2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 27890Article in journal (Refereed) Published
Abstract [en]

Ultraviolet (UV) irradiation induces skin pigmentation, which relies on the intercellular crosstalk of melanin between melanocytes to keratinocytes. However, studying the separate effects of UVA and UVB irradiation reveals differences in cellular response. Herein, we show an immediate shedding of extracellular vesicles (EVs) from the plasma membrane when exposing human melanocytes to UVA, but not UVB. The EV-shedding is preceded by UVA-induced plasma membrane damage, which is rapidly repaired by Ca2+-dependent lysosomal exocytosis. Using co-cultures of melanocytes and keratinocytes, we show that EVs are preferably endocytosed by keratinocytes. Importantly, EV-formation is prevented by the inhibition of exocytosis and increased lysosomal pH but is not affected by actin and microtubule inhibitors. Melanosome transfer from melanocytes to keratinocytes is equally stimulated by UVA and UVB and depends on a functional cytoskeleton. In conclusion, we show a novel cell response after UVA irradiation, resulting in transfer of lysosome-derived EVs from melanocytes to keratinocytes.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2016
National Category
Cell Biology
Identifiers
urn:nbn:se:liu:diva-130287 (URN)10.1038/srep27890 (DOI)000378036300001 ()27293048 (PubMedID)
Note

Funding Agencies|Swedish Research Council; Swedish Cancer Society; Welander-Finsen Foundation; County Council of Ostergotland; Stiftelsen Olle Engkvist Byggmastare; Konung Gustav V och Drottning Victorias Frimurarestiftelse; Ostgotaregionens Cancerfond

Available from: 2016-08-01 Created: 2016-07-28 Last updated: 2017-11-28
Klionsky, D. J., Boman, A., Kågedal, K., Kurz, T., Mohseni, S., Öllinger, K. & Zughaier, S. M. (2016). Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy, 2(1), 1-222
Open this publication in new window or tab >>Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
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2016 (English)In: Autophagy, ISSN 1554-8627, E-ISSN 1554-8635, Vol. 2, no 1, p. 1-222Article, review/survey (Refereed) Published
Place, publisher, year, edition, pages
Taylor & Francis, 2016
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-137050 (URN)10.1080/15548627.2015.1100356 (DOI)000373595400001 ()26799652 (PubMedID)
Note

The article contains 2467 authors of which five are affiliated with LiU and have the following author order:

Author no. 177: Andrea Boman

Author no. 968: Katarina Kågedal

Author no. 1106: Tino Kurz

Author no. 1449: Simin Mohseni

Author no. 1559: Karin Öllinger

Available from: 2017-05-02 Created: 2017-05-02 Last updated: 2019-03-14Bibliographically approved
Södergren, A., Svensson Holm, A.-C., Ramström, S., Lindström, E., Grenegård, M. & Öllinger, K. (2016). Thrombin-induced lysosomal exocytosis in human platelets is dependent on secondary activation by ADP and regulated by endothelial-derived substances. Platelets, 27(1), 86-92
Open this publication in new window or tab >>Thrombin-induced lysosomal exocytosis in human platelets is dependent on secondary activation by ADP and regulated by endothelial-derived substances
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2016 (English)In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 27, no 1, p. 86-92Article in journal (Refereed) Published
Abstract [en]

Exocytosis of lysosomal contents from platelets has been speculated to participate in clearance of thrombi and vessel wall remodelling. The mechanisms that regulate lysosomal exocytosis in platelets are, however, still unclear. The aim of this study was to identify the pathways underlying platelet lysosomal secretion and elucidate how this process is controlled by platelet inhibitors. We found that high concentrations of thrombin induced partial lysosomal exocytosis as assessed by analysis of the activity of released N-acetyl--glucosaminidase (NAG) and by identifying the fraction of platelets exposing the lysosomal-associated membrane protein (LAMP)-1 on the cell surface by flow cytometry. Stimulation of thrombin receptors PAR1 or PAR4 with specific peptides was equally effective in inducing LAMP-1 surface expression. Notably, lysosomal exocytosis in response to thrombin was significantly reduced if the secondary activation by ADP was inhibited by the P2Y(12) antagonist cangrelor, while inhibition of thromboxane A(2) formation by treatment with acetylsalicylic acid was of minor importance in this regard. Moreover, the NO-releasing drug S-nitroso-N-acetyl penicillamine (SNAP) or the cyclic AMP-elevating eicosanoid prostaglandin I-2 (PGI(2)) significantly suppressed lysosomal exocytosis. We conclude that platelet inhibitors that mimic functional endothelium such as PGI(2) or NO efficiently counteract lysosomal exocytosis. Furthermore, we suggest that secondary release of ADP and concomitant signaling via PAR1/4- and P2Y(12) receptors is important for efficient platelet lysosomal exocytosis by thrombin.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS INC, 2016
Keywords
ADP receptors; endothelium; exocytosis; lysosome; platelet physiology; protease activated receptors (PAR); thrombin
National Category
Clinical Medicine Biological Sciences
Identifiers
urn:nbn:se:liu:diva-125318 (URN)10.3109/09537104.2015.1042446 (DOI)000368717700011 ()25970449 (PubMedID)
Note

Funding Agencies|County Council of Ostergotland; Swedish Research Council

Available from: 2016-02-24 Created: 2016-02-19 Last updated: 2018-10-25
Bivik Eding, C., Domer, J., Wäster, P., Jerhammar, F., Rosdahl, I. & Öllinger, K. (2015). Melanoma Growth and Progression After Ultraviolet A Irradiation: Impact of Lysosomal Exocytosis and Cathepsin Proteases. Acta Dermato-Venereologica, 95(7), 792-797
Open this publication in new window or tab >>Melanoma Growth and Progression After Ultraviolet A Irradiation: Impact of Lysosomal Exocytosis and Cathepsin Proteases
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2015 (English)In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 95, no 7, p. 792-797Article in journal (Refereed) Published
Abstract [en]

Ultraviolet (UV) irradiation is a risk factor for development of malignant melanoma. UVA-induced lysosomal exocytosis and subsequent cell growth enhancement was studied in malignant melanoma cell lines and human skin melanocytes. UVA irradiation caused plasma membrane damage that was rapidly repaired by calcium-dependent lysosomal exocytosis. Lysosomal content was released into the culture medium directly after irradiation and such conditioned media stimulated the growth of non-irradiated cell cultures. By comparing melanocytes and melanoma cells, it was found that only the melanoma cells spontaneously secreted cathepsins into the surrounding medium. Melanoma cells from a primary tumour showed pronounced invasion ability, which was prevented by addition of inhibitors of cathepsins B, D and L. Proliferation was reduced by cathepsin L inhibition in all melanoma cell lines, but did not affect melanocyte growth. In conclusion, UVA-induced release of cathepsins outside cells may be an important factor that promotes melanoma growth and progression.

Place, publisher, year, edition, pages
ACTA DERMATO-VENEREOLOGICA, 2015
Keywords
lysosome; cathepsin; UVA; exocytosis; melanocyte; melanoma
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:liu:diva-122545 (URN)10.2340/00015555-2064 (DOI)000362925500005 ()25669167 (PubMedID)
Note

Funding Agencies|Swedish Research Council; Ostgotaregionens Cancer Foundation; Stiftelsen Olle Engkvist Byggmastare; Swedish Cancer Society; Welander-Finsen Foundation

Available from: 2015-11-06 Created: 2015-11-06 Last updated: 2017-12-01
Wäster, P., Rosdahl, I. & Öllinger, K. (2014). Cell fate regulated by nuclear factor-κB- and activator protein-1-dependent signalling in human melanocytes exposed to ultraviolet A and ultraviolet B.. British Journal of Dermatology, 171(6), 1336-1346
Open this publication in new window or tab >>Cell fate regulated by nuclear factor-κB- and activator protein-1-dependent signalling in human melanocytes exposed to ultraviolet A and ultraviolet B.
2014 (English)In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 171, no 6, p. 1336-1346Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Ultraviolet (UV) radiation constitutes an important risk factor for malignant melanoma, but the wavelength responsible for the initiation of this disease is not fully elucidated. Solar UV induces multiple signalling pathways that are critical for initiation of apoptotic cell death as a cellular defence against malignant transformation.

OBJECTIVES: To evaluate the involvement of the transcription factors nuclear factor (NF)-κB and activator protein (AP)-1 in the signalling pathways induced by UVA or UVB irradiation in human melanocytes.

METHODS: Primary cultures of normal human melanocytes were irradiated with UVA or UVB, and the concomitant DNA damage and redox alterations were monitored. The resulting activation of the NF-κB and AP-1 signalling pathways and subsequent apoptosis were studied.

RESULTS: UVB irradiation causes DNA damage detected as formation of cyclobutane pyrimidine dimers, while UVA induces increased levels of 8-hydroxydeoxyguanosine and lipid peroxidation. UVA and UVB initiate phosphorylation of c-Jun N-terminal protein kinase and extracellular signal-regulated kinase, and the apoptosis signalling pathways converge into a common mechanism. Downregulation of c-Jun suppresses AP-1-mediated signalling and prevents apoptosis upstream of lysosomal and mitochondrial membrane permeabilization, whereas inhibition of NF-κB by SN50 increases apoptosis.

CONCLUSIONS: We conclude that AP-1 induces proapoptotic signalling, whereas NF-κB is a key antiapoptotic/prosurvival factor in both UVA- and UVB-induced cellular damage in human melanocytes, which might in turn impact melanoma development and progression.

Place, publisher, year, edition, pages
John Wiley & Sons, 2014
National Category
Clinical Medicine Basic Medicine
Identifiers
urn:nbn:se:liu:diva-112883 (URN)10.1111/bjd.13278 (DOI)000347236100174 ()25046326 (PubMedID)
Note

Funding text:

This study was supported by the Swedish Research Council, the Swedish Cancer Society, the County Council of Ostergotland, Konung Gustav V och Drottning Victorias Frimurarestiftelse and the Welander-Finsen Foundation.

Available from: 2014-12-18 Created: 2014-12-18 Last updated: 2018-01-11Bibliographically approved
Svensson Holm, A.-C., Grenegård, M., Ollinger, K. & Lindström, E. (2014). Inhibition of 12-lipoxygenase reduces platelet activation and prevents their mitogenic function. Platelets, 25(2), 111-117
Open this publication in new window or tab >>Inhibition of 12-lipoxygenase reduces platelet activation and prevents their mitogenic function
2014 (English)In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 25, no 2, p. 111-117Article in journal (Refereed) Published
Abstract [en]

The aim of the present study was to investigate the role of 12-lipoxygenase (12-LOX) on platelet-induced airway smooth muscle cell (ASMC) proliferation. Co-incubation of platelets and ASMC caused platelet activation as determined by morphological changes. Simultaneously, reactive oxygen species (ROS)-generation was detected and ASMC proliferation (measured by using the MTS assay) increased significantly. Furthermore, we found that the 12-LOX inhibitors cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC) and Baicalein prevented platelet activation in a co-cultures of platelets and ASMC. The inhibitory effect of CDC and Baicalein on platelets was also registered in a pure platelet preparation. Specifically, the 12-LOX inhibitors reduced collagen-induced platelet aggregation both in the presence and absence of external added fibrinogen. Importantly, platelet-induced ASMC proliferation and ROS production generated during the platelet/ASMC interaction was significantly inhibited in the presence of 12-LOX inhibitors. In conclusion, our findings reveal that 12-LOX is crucial for the observed enhancement of ASMC proliferation in co-cultures of platelets and ASMC. The present result suggests that 12-LOX activity is important in the initial step of platelet/ASMC interaction and platelet activation. Such action of 12-LOX represents a potential important mechanism that may contribute to platelet-induced airway remodelling.

Place, publisher, year, edition, pages
Informa Healthcare, 2014
Keywords
12-lipoxygenase, airway remodelling, airway smooth muscle, platelet-induced proliferation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-99371 (URN)10.3109/09537104.2013.783688 (DOI)000331905100006 ()23534390 (PubMedID)
Available from: 2013-10-16 Created: 2013-10-16 Last updated: 2017-12-06Bibliographically approved
Kishwar, S., Siddique, M., Israr, M. Q., Nour, O., Willander, M. & Öllinger, K. (2014). Investigation of the phototoxic effect of ZnO nanorods on fibroblasts and melanoma human cells. Laser Physics Letters, 11(11), Article ID 115606.
Open this publication in new window or tab >>Investigation of the phototoxic effect of ZnO nanorods on fibroblasts and melanoma human cells
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2014 (English)In: Laser Physics Letters, ISSN 1612-2011, E-ISSN 1612-202X, Vol. 11, no 11, article id 115606Article in journal (Refereed) Published
Abstract [en]

Photo-cytotoxicity of zinc oxide (ZnO) nanowires (NWs) either bare or conjugated with photosensitizers was studied in dark and after ultraviolet light exposure, in human melanoma and foreskin fibroblast cells. ZnO NWs were grown on the capillary tip and then coated with photosensitizer. This coated tip was used as pointer for intracellular insertion of ZnO NWs and photosensitizer. ZnO NWs pointer was inserted into a specific cell and then irradiated with ultraviolet (UVA), which led to loss of mitochondrial membrane potential, as estimated by loss of the Mitotracker Red staining. Dissolved ZnO NWs showed cytotoxicity as detected by MTT viability assay and morphological evaluation. UVA-irradiation enhanced the toxicity and caused the production of reactive oxygen species (ROS) resulting in cell necrosis. ZnO NWs were photo-toxic for both normal and cancer cells, questioning their bio-safety.

Place, publisher, year, edition, pages
Institute of Physics (IOP), 2014
Keywords
ZnO nanowires, photodynamic therapy, reactive oxygen species, δ- Aminolevulinic acid, protoporphyrin 1X
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-71316 (URN)10.1088/1612-2011/11/11/115606 (DOI)000345221100016 ()
Note

The previous status of this article was Manuscript and the working title was Photo toxicity of Zinc Oxide Nanowires in Human Melanoma and Fibroblast Cells.

Available from: 2011-10-11 Created: 2011-10-11 Last updated: 2018-07-19Bibliographically approved
Villamil Giraldo, A. M., Appelqvist, H., Ederth, T. & Öllinger, K. (2014). Lysosomotropic agents: impact on lysosomal membrane permeabilization and cell death. Biochemical Society Transactions, 42, 1460-1464
Open this publication in new window or tab >>Lysosomotropic agents: impact on lysosomal membrane permeabilization and cell death
2014 (English)In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 42, p. 1460-1464Article in journal (Refereed) Published
Abstract [en]

Lysosomes are acidic organelles essential for degradation, signalling and cell homoeostasis. In addition, they play a key role in cell death. Permeabilization of the lysosomal membrane and release of hydrolytic enzymes to the cytosol accompanies apoptosis signalling in several systems. The regulatory mechanism of lysosomal stability is, however, poorly understood. Lipophilic or amphiphilic compounds with a basic moiety will become protonated and trapped within lysosomes, and such lysosomotropic behaviour is also found in many pharmacological drugs. The natural sphingolipid sphingosine exhibits lysosomotropic detergent ability and is an endogenous candidate for controlling lysosomal membrane permeabilization. The lysosomotropic properties of certain detergents might be of use in lysosome-targeting anticancer drugs and drug delivery system in the future. The present review summarizes the current knowledge on the targeting and permeabilizing properties of lysosomotropic detergents from a cellular and physicochemical perspective.

Place, publisher, year, edition, pages
Portland Press, 2014
Keywords
detergent; lysosome; lysosomal membrane; O-methyl-serine dodecylamine hydrochloride (MSDH); permeabilization; sphingosine
National Category
Chemical Sciences Physical Sciences Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-111745 (URN)10.1042/BST20140145 (DOI)000342566700032 ()25233432 (PubMedID)
Note

Funding Agencies|Swedish Research Council [3214]; Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse

Available from: 2014-10-31 Created: 2014-10-31 Last updated: 2017-12-05
Wäster, P., Eriksson, I., Vainikka, L. & Öllinger, K. (2014). Sunbathing: What’ve lysosomes got to do with it?. Communicative & Integrative Biology, 7(1), e28723-1-e28723-5
Open this publication in new window or tab >>Sunbathing: What’ve lysosomes got to do with it?
2014 (English)In: Communicative & Integrative Biology, ISSN 1942-0889, E-ISSN 1942-0889, Vol. 7, no 1, p. e28723-1-e28723-5Article in journal (Refereed) Published
Abstract [en]

Solar radiation is an important risk factor for skin cancer, the incidence of which is increasing, especially in the fair-skinned populations of the world. While the ultraviolet (UV)B component has direct DNA damaging ability, UVA-induced effects are currently mainly attributed to the production of reactive oxygen species. In our recent study, we compared the effects of UVA and UVB radiation on human keratinocytes and found that UVA-induced plasma membrane damage was rapidly repaired by lysosomal exocytosis, which was detected based on the expression of lysosomal membrane associated protein-1 (LAMP-1) on the plasma membrane of non-permeabilized cells. Later, the keratinocytes died through caspase-8 mediated apoptosis. In contrast, the plasma membranes of keratinocytes exposed to UVB showed no LAMP-1 expression, and, although the cells died by apoptosis, no initial caspase-8 activity was detected. We have also demonstrated the occurrence of UVA-induced lysosomal exocytosis in reconstructed skin and shown the relocation of lysosomes from the center of cells to the vicinity of the plasma membrane. Thus, we suggest that lysosomal exocytosis also occurs in keratinocytes covered by the stratum corneum following exposure to UVA. Our findings provide new insight into the mechanism of UVA-induced skin damage.

Place, publisher, year, edition, pages
Austin, Texas, USA: Landes Biosciences, 2014
Keywords
UV irradiation, keratinocytes, lysosomes, exocytosis, plasma membrane repair, lysosomal, associated membrane protein
National Category
Basic Medicine Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-107147 (URN)10.4161/cib.28723 (DOI)25346791 (PubMedID)2-s2.0-84902664460 (Scopus ID)
Note

Article Addendum to: H Appelqvist, P Waster, I Eriksson, I Rosdahl, K Ollinger. Lysosomal exocytosis and caspase-8-mediated apoptosis in UVA-irradiated keratinocytes. Journal of Cell Science 2013; 126: 5578- 5584. DOI: 10.1242/jcs.130633

Available from: 2014-06-05 Created: 2014-06-05 Last updated: 2018-01-11Bibliographically approved
Appelqvist, H., Wäster, P., Eriksson, I., Rosdahl, I. & Öllinger, K. (2013). Lysosomal exocytosis and caspase-8-mediated apoptosis in UVA-irradiated keratinocytes. Journal of Cell Science, 126(24), 5578-5584
Open this publication in new window or tab >>Lysosomal exocytosis and caspase-8-mediated apoptosis in UVA-irradiated keratinocytes
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2013 (English)In: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 126, no 24, p. 5578-5584Article in journal (Refereed) Published
Abstract [en]

Ultraviolet (UV) irradiation is a major environmental carcinogen involved in the development of skin cancer. To elucidate the initial signaling during UV-induced damage in human keratinocytes, we investigated lysosomal exocytosis and apoptosis induction. UVA, but not UVB, induced plasma membrane damage, which was repaired by Ca2+-dependent lysosomal exocytosis. The lysosomal exocytosis resulted in extracellular release of cathepsin D and acid sphingomyelinase (aSMase). Two hours after UVA irradiation, we detected activation of caspase-8, which was reduced by addition of anti-aSMAse. Furthermore, caspase-8 activation and apoptosis was reduced by prevention of endocytosis and by the use of cathepsin inhibitors. We conclude that lysosomal exocytosis is part of the keratinocyte response to UVA and is followed by cathepsin-dependent activation of caspase-8. The findings have implications for the understanding of UV-induced skin damage and emphasize that UVA and UVB initiate apoptosis through different signaling pathways in keratinocytes.

Place, publisher, year, edition, pages
Company of Biologists, 2013
Keywords
Keratinocyte; UV irradiation; Lysosome; Cathepsin; Endocytosis; Apoptosis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-103290 (URN)10.1242/jcs.130633 (DOI)000328686600005 ()
Note

The previous status of this article was manuscript with the title Lysosomal exocytosis repairs the plasma membrane after UVA and is followed by caspase-8 induced apoptosis.

Available from: 2014-01-17 Created: 2014-01-16 Last updated: 2017-08-30
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ORCID iD: ORCID iD iconorcid.org/0000-0003-4075-159x

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