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Wicher, Grzegorz K.
Alternative names
Publications (10 of 11) Show all publications
Karademir, B., Sari, G., Jannuzzi, A. T., Musunuri, S., Wicher, G., Grune, T., . . . Jung, T. (2018). Proteomic approach for understanding milder neurotoxicity of Carfilzomib against Bortezomib. Scientific Reports, 8, Article ID 16318.
Open this publication in new window or tab >>Proteomic approach for understanding milder neurotoxicity of Carfilzomib against Bortezomib
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 16318Article in journal (Refereed) Published
Abstract [en]

The proteasomal system is responsible for the turnover of damaged proteins. Because of its important functions in oncogenesis, inhibiting the proteasomal system is a promising therapeutic approach for cancer treatment. Bortezomib (BTZ) is the first proteasome inhibitor approved by FDA for clinical applications. However neuropathic side effects are dose limiting for BTZ as many other chemotherapeutic agents. Therefore second-generation proteasome inhibitors have been developed including carfilzomib (CFZ). Aim of the present work was investigating the mechanisms of peripheral neuropathy triggered by the proteasome inhibitor BTZ and comparing the pathways affected by BTZ and CFZ, respectively. Neural stem cells, isolated from the cortex of E14 mouse embryos, were treated with BTZ and CFZ and mass spectrometry was used to compare the global protein pool of treated cells. BTZ was shown to cause more severe cytoskeletal damage, which is crucial in neural cell integrity. Excessive protein carbonylation and actin filament destabilization were also detected following BTZ treatment that was lower following CFZ treatment. Our data on cytoskeletal proteins, chaperone system, and protein oxidation may explain the milder neurotoxic effects of CFZ in clinical applications.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2018
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-369397 (URN)10.1038/s41598-018-34507-3 (DOI)000449272100012 ()30397214 (PubMedID)
Funder
Swedish Research Council, 2015-4870
Available from: 2018-12-12 Created: 2018-12-12 Last updated: 2018-12-12Bibliographically approved
Wicher, G. K., Wallenquist, U., Lei, Y., Enoksson, M., Li, X., Fuchs, B., . . . Forsberg Nilsson, K. (2017). Interleukin-33 Promotes Recruitment of Microglia/Macrophages in Response to Traumatic Brain Injury. Journal of Neurotrauma, 34(22), 3173-3182
Open this publication in new window or tab >>Interleukin-33 Promotes Recruitment of Microglia/Macrophages in Response to Traumatic Brain Injury
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2017 (English)In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 34, no 22, p. 3173-3182Article in journal (Refereed) Published
Abstract [en]

Traumatic brain injury (TBI) is a devastating condition, often leading to life-long consequences for patients. Even though modern neurointensive care has improved functional and cognitive outcomes, efficient pharmacological therapies are still lacking. Targeting peripherally derived, or resident inflammatory, cells that are rapid responders to brain injury is promising, but complex, given that the contribution of inflammation to exacerbation versus improved recovery varies with time post-injury. The injury-induced inflammatory response is triggered by release of alarmins, and in the present study we asked whether interleukin-33 (IL-33), an injury-associated nuclear alarmin, is involved in TBI. Here, we used samples from human TBI microdialysate, tissue sections from human TBI, and mouse models of central nervous system injury and found that expression of IL-33 in the brain was elevated from nondetectable levels, reaching a maximum after 72 h in both human samples and mouse models. Astrocytes and oligodendrocytes were the main producers of IL-33. Post-TBI, brains of mice deficient in the IL-33 receptor, ST2, contained fewer microglia/macrophages in the injured region than wild-type mice and had an altered cytokine/chemokine profile in response to injury. These observations indicate that IL-33 plays a role in neuroinflammation with microglia/macrophages being cellular targets for this interleukin post-TBI.

Keywords
alarmin, glia, microglia, traumatic brain injury, neuroinflammation
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-341988 (URN)10.1089/neu.2016.4900 (DOI)000414560000013 ()28490277 (PubMedID)
Funder
Swedish Research Council
Available from: 2018-02-16 Created: 2018-02-16 Last updated: 2018-07-13Bibliographically approved
Sari-Kaplan, G., Musunuri, S., Wicher, G., Jung, T., Mi, J., Hacioglu-Bay, H., . . . Karademir, B. (2016). Peripheral neuropathy as the side effect of proteasome inhibitors bortezomib and carfilzomib. Paper presented at Conference of the Society-for-Free-Radical-Research-Europe (SFRR-E), JUN 08-11, 2016, Budapest, HUNGARY. Free Radical Biology & Medicine, 96, S17-S17
Open this publication in new window or tab >>Peripheral neuropathy as the side effect of proteasome inhibitors bortezomib and carfilzomib
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2016 (English)In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 96, p. S17-S17Article in journal, Meeting abstract (Other academic) Published
National Category
Endocrinology and Diabetes Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-300129 (URN)10.1016/j.freeradbiomed.2016.04.154 (DOI)000377617900040 ()
Conference
Conference of the Society-for-Free-Radical-Research-Europe (SFRR-E), JUN 08-11, 2016, Budapest, HUNGARY
Available from: 2016-08-03 Created: 2016-08-03 Last updated: 2017-11-28Bibliographically approved
Wicher, G. & Norlin, M. (2015). Estrogen-mediated regulation of steroid metabolism in rat glial cells; effects on neurosteroid levels via regulation of CYP7B1-mediated catalysis. Journal of Steroid Biochemistry and Molecular Biology, 145, 21-27
Open this publication in new window or tab >>Estrogen-mediated regulation of steroid metabolism in rat glial cells; effects on neurosteroid levels via regulation of CYP7B1-mediated catalysis
2015 (English)In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 145, p. 21-27Article in journal (Refereed) Published
Abstract [en]

Many neuroactive steroids, including dehydroepiandrosterone (DHEA), pregnenolone, 27-hydroxycholesterol and 17 beta-estradiol, are known to affect development and function of the brain and nervous system. These and other steroids can undergo tissue and/or cell-specific enzymatic conversions into steroid metabolites. Carefully regulated production of steroids with various physiological effects is important for cells of the nervous system. Astrocytes express many steroidogenic enzymes and are considered important producers of brain steroids. The quantitative roles of different pathways for steroid metabolism in rat astrocytes are not clear. In the current study we examined effects of estrogens on steroid metabolism catalyzed by CYP7B1 and other enzymes in primary cultures of rat astrocytes. The CYP7B1 enzyme, which has been linked to neurodegenerative disease, is involved in the metabolism of several important neurosteroids. In the present study, we found that 7 alpha-hydroxylation, performed by CYP7B1, is the quantitatively most important pathway for DHEA metabolism in rat astrocytes. In addition, our present experiments on catalytic steroid conversions revealed that estrogens significantly suppress the CYP7B1-catalyzed metabolism of not only DHEA but also of pregnenolone and 27-hydroxycholesterol in rat astrocytes. These novel findings point to a regulatory mechanism for control of the cellular levels of these neurosteroids via CYP7B1. Our hypothesis that estrogens can regulate neurosteroid levels via this enzymatic reaction was supported by experiments using ELISA to assay levels of DHEA and pregnenolone in the presence or absence of estrogen. Furthermore, the present results show that estrogen suppresses CYP7B1-catalyzed 7 alpha-hydroxylation also in primary cultures of rat Schwann cells, indicating that regulation by estrogen via this enzyme may be of relevance in both the CNS and the PNS. 

Keywords
Sex hormone, Nervous system, Astrocytes, Schwann cells, Neurosteroid metabolism
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-246670 (URN)10.1016/j.jsbmb.2014.09.022 (DOI)000347771400003 ()25263657 (PubMedID)
Available from: 2015-03-18 Created: 2015-03-09 Last updated: 2017-12-04Bibliographically approved
Corell, M., Wicher, G., Radomska, K. J., Dağlıkoca, E. D., Godskesen, R. E., Fredriksson, R., . . . Fex Svenningsen, Å. (2015). GABA and its B-receptor are present at the node of Ranvier in a small population of sensory fibers, implicating a role in myelination. Journal of Neuroscience Research, 93(2), 285-295
Open this publication in new window or tab >>GABA and its B-receptor are present at the node of Ranvier in a small population of sensory fibers, implicating a role in myelination
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2015 (English)In: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547, Vol. 93, no 2, p. 285-295Article in journal (Refereed) Published
Abstract [en]

The γ-aminobutyric acid (GABA) type B receptor has been implicated in glial cell development in the peripheral nervous system (PNS), although the exact function of GABA signaling is not known. To investigate GABA and its B receptor in PNS development and degeneration, we studied the expression of the GABAB receptor, GABA, and glutamic acid decarboxylase GAD65/67 in both development and injury in fetal dissociated dorsal root ganglia (DRG) cell cultures and in the rat sciatic nerve. We found that GABA, GAD65/67, and the GABAB receptor were expressed in premyelinating and nonmyelinating Schwann cells throughout development and after injury. A small population of myelinated sensory fibers displayed all of these molecules at the node of Ranvier, indicating a role in axon-glia communication. Functional studies using GABAB receptor agonists and antagonists were performed in fetal DRG primary cultures to study the function of this receptor during development. The results show that GABA, via its B receptor, is involved in the myelination process but not in Schwann cell proliferation. The data from adult nerves suggest additional roles in axon-glia communication after injury.

National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-238740 (URN)10.1002/jnr.23489 (DOI)000346475600008 ()25327365 (PubMedID)
Available from: 2014-12-16 Created: 2014-12-16 Last updated: 2018-01-11Bibliographically approved
Sari, G., Musuruni, S., Wicher, G., Mi, J., Bergquist, J. & Karademir, B. (2015). Heat shock proteins in proteasome inhibitor related neuropathy. Paper presented at SFRR-E/SNFS Conference, SEP 02-04, 2015, Stuttgart, GERMANY. Free Radical Biology & Medicine, 86(Suppl. 1), S27-S27
Open this publication in new window or tab >>Heat shock proteins in proteasome inhibitor related neuropathy
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2015 (English)In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 86, no Suppl. 1, p. S27-S27Article in journal, Meeting abstract (Other academic) Published
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-264918 (URN)10.1016/j.freeradbiomed.2015.07.099 (DOI)000360568700068 ()
Conference
SFRR-E/SNFS Conference, SEP 02-04, 2015, Stuttgart, GERMANY
Note

Meeting Abstract: PP24

Available from: 2015-11-02 Created: 2015-10-19 Last updated: 2017-12-01Bibliographically approved
Xie, Y., Bergström, T., Jiang, Y., Johansson, P., Marinescu, V. D., Lindberg, N., . . . Uhrbom, L. (2015). The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes. EBioMedicine, 2(10), 1351-1363
Open this publication in new window or tab >>The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes
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2015 (English)In: EBioMedicine, E-ISSN 2352-3964, Vol. 2, no 10, p. 1351-1363Article in journal (Refereed) Published
Abstract [en]

Glioblastoma (GBM) is the most frequent and malignant form of primary brain tumor. GBM is essentially incurable and its resistance to therapy is attributed to a subpopulation of cells called gliomastem cells (GSCs). To meet the present shortage of relevant GBM cell (GC) lines we developed a library of annotated and validated cell lines derived from surgical samples of GBM patients, maintained under conditions to preserve GSC characteristics. This collection, which we call the Human Glioblastoma Cell Culture (HGCC) resource, consists of a biobank of 48 GC lines and an associated database containing high-resolution molecular data. We demonstrate that the HGCC lines are tumorigenic, harbor genomic lesions characteristic of GBMs, and represent all four transcriptional sub-types. The HGCC panel provides an open resource for in vitro and in vivo modeling of a large part of GBM diversity useful to both basic and translational GBM research.

Keywords
Glioblastoma, Cell culture, Stem cell culture condition, Molecular subtype, Xenograft models
National Category
Cancer and Oncology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Clinical Laboratory Medicine
Research subject
Pathology; Pathology
Identifiers
urn:nbn:se:uu:diva-274354 (URN)10.1016/j.ebiom.2015.08.026 (DOI)000365959700034 ()26629530 (PubMedID)
Note

De två sista författarna delar sistaförfattarskapet.

Available from: 2016-01-21 Created: 2016-01-21 Last updated: 2019-04-02Bibliographically approved
Wicher, G., Husic, E., Nilsson, G. & Forsberg-Nilsson, K. (2013). Developmental expression of IL-33 in the mouse brain. Neuroscience Letters, 555, 171-176
Open this publication in new window or tab >>Developmental expression of IL-33 in the mouse brain
2013 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 555, p. 171-176Article in journal (Refereed) Published
Abstract [en]

IL-33 has important functions in inflammatory and autoimmune diseases. In the brain, models of experimental encephalomyelitis are accompanied by up-regulation of IL-33 expression, and the cytokine is seen as an amplifier of the innate immune response. Little is known, however, about IL-33 the normal brain in adult life, or during development. We have analyzed the expression of IL-33 in the mouse brain during embryonic and postnatal development. Here we report that IL-33 expression was first detected in the CNS during late embryogenesis. From postnatal day 2 (P2) until P9 the expression increased and was strongest in the cerebellum, pons and thalamus, as well as in olfactory bulbs. Expression of IL-33 then became weaker and declined until P23, and it was not present in the adult brain. Both astrocytes and oligodendrocyte precursors expressed IL-33. The vast majority of IL-33 positive cells in the brain displayed nuclear staining, and this was found to be the case also in vitro, using mixed glial cultures. Our data suggest that IL-33 expression is under tight regulation in the normal brain. Its detection during the first three weeks of postnatal life coincides with important parts of the CNS developmental programs, such as general growth and myelination. This opens the possibility that IL-33 plays a role also in the absence of an inflammatory response.

Keywords
Alarmin, Astrocytes, Glia, Development, Neuroinflammation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-213997 (URN)10.1016/j.neulet.2013.09.046 (DOI)000327825600032 ()
Available from: 2014-01-07 Created: 2014-01-06 Last updated: 2017-08-17Bibliographically approved
Wicher, G., Wallenquist, U., Enoksson, M., Fuchs, B., Husic, E., Hillered, L., . . . Forsberg Nilsson, K. (2013). Interleukin-33 in brain development and traumatic brain injury. Paper presented at 11th European Meeting on Glial Cell Function in Health and Disease, JUL 03-06, 2013, Berlin, GERMANY. Glia, 61(S1), S185-S185
Open this publication in new window or tab >>Interleukin-33 in brain development and traumatic brain injury
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2013 (English)In: Glia, ISSN 0894-1491, E-ISSN 1098-1136, Vol. 61, no S1, p. S185-S185Article in journal, Meeting abstract (Other academic) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-204188 (URN)000320408400594 ()
Conference
11th European Meeting on Glial Cell Function in Health and Disease, JUL 03-06, 2013, Berlin, GERMANY
Available from: 2013-07-23 Created: 2013-07-23 Last updated: 2017-08-18
Enoksson, M., Möller-Westerberg, C., Wicher, G., Fallon, P. G., Forsberg-Nilsson, K., Lunderius-Andersson, C. & Nilsson, G. (2013). Intraperitoneal influx of neutrophils in response to IL-33 is mast cell-dependent. Blood, 121(3), 530-536
Open this publication in new window or tab >>Intraperitoneal influx of neutrophils in response to IL-33 is mast cell-dependent
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2013 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 121, no 3, p. 530-536Article in journal (Refereed) Published
Abstract [en]

IL-33 is a recently discovered cytokine involved in induction of Th2 responses and functions as an alarmin. Despite numerous recent studies targeting IL-33, its role in vivo is incompletely understood. Here we investigated inflammatory responses to intraperitoneal IL-33 injections in wild-type and mast cell–deficient mice. We found that wild-type mice, but not mast cell–deficient Wsh/Wsh mice, respond to IL-33 treatment with neutrophil infiltration to the peritoneum, whereas other investigated cell types remained unchanged. In Wsh/Wsh mice, the IL-33–induced innate neutrophil response could be rescued by local reconstitution with wild-type but not with T1/ST2−/− mast cells, demonstrating a mast cell–dependent mechanism. Furthermore, we found this mechanism to be partially dependent on mast cell–derived TNF, as we observed reduced neutrophil infiltration in Wsh/Wsh mice reconstituted with TNF−/− bone marrow–derived mast cells compared with those reconstituted with wild-type bone marrow–derived mast cells. In agreement with our in vivo findings, we demonstrate that humanneutrophils migrate toward the supernatant of IL-33–treated human mast cells. Taken together, our findings reveal that IL-33 activates mast cells in vivo to recruit neutrophils, a mechanism dependent on IL-33R expression on peritoneal mast cells. Mast cells activated in vivo by IL-33 probably play an important role in inflammatory reactions.

National Category
Basic Medicine Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-191129 (URN)10.1182/blood-2012-05-434209 (DOI)000313727500017 ()23093619 (PubMedID)
Available from: 2013-01-09 Created: 2013-01-09 Last updated: 2018-01-11Bibliographically approved
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