Can, Karolina

[["dc.bibliographiccitation.artnumber","479"],["dc.bibliographiccitation.journal","Frontiers in Physiology"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Can, Karolina"],["dc.contributor.author","Menzfeld, Christiane"],["dc.contributor.author","Rinne, Lena"],["dc.contributor.author","Rehling, Peter"],["dc.contributor.author","Kügler, Sebastian"],["dc.contributor.author","Golubiani, Gocha"],["dc.contributor.author","Dudek, Jan"],["dc.contributor.author","Müller, Michael"],["dc.date.accessioned","2019-07-09T11:51:15Z"],["dc.date.available","2019-07-09T11:51:15Z"],["dc.date.issued","2019"],["dc.description.abstract","Rett syndrome (RTT), an X chromosome-linked neurodevelopmental disorder affecting almost exclusively females, is associated with various mitochondrial alterations. Mitochondria are swollen, show altered respiratory rates, and their inner membrane is leaking protons. To advance the understanding of these disturbances and clarify their link to redox impairment and oxidative stress, we assessed mitochondrial respiration in defined brain regions and cardiac tissue of male wildtype (WT) and MeCP2-deficient (Mecp2-/y) mice. Also, we quantified for the first time neuronal redox-balance with subcellular resolution in cytosol and mitochondrial matrix. Quantitative roGFP1 redox imaging revealed more oxidized conditions in the cytosol of Mecp2-/y hippocampal neurons than in WT neurons. Furthermore, cytosol and mitochondria of Mecp2-/y neurons showed exaggerated redox-responses to hypoxia and cell-endogenous reactive oxygen species (ROS) formation. Biochemical analyzes exclude disease-related increases in mitochondrial mass in Mecp2-/y hippocampus and cortex. Protein levels of complex I core constituents were slightly lower in Mecp2-/y hippocampus and cortex than in WT; those of complex V were lower in Mecp2-/y cortex. Respiratory supercomplex-formation did not differ among genotypes. Yet, supplied with the complex II substrate succinate, mitochondria of Mecp2-/y cortex and hippocampus consumed more O2 than WT. Furthermore, mitochondria from Mecp2-/y hippocampus and cortex mediated an enhanced oxidative burden. In conclusion, we further advanced the molecular understanding of mitochondrial dysfunction in RTT. Intensified mitochondrial O2 consumption, increased mitochondrial ROS generation and disturbed redox balance in mitochondria and cytosol may represent a causal chain, which provokes dysregulated proteins, oxidative tissue damage, and contributes to neuronal network dysfunction in RTT."],["dc.identifier.doi","10.3389/fphys.2019.00479"],["dc.identifier.pmid","31114506"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16085"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59907"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/12"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | A06: Mitochondrienfunktion und -umsatz in Synapsen"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","573"],["dc.subject.ddc","612"],["dc.title","Neuronal Redox-Imbalance in Rett Syndrome Affects Mitochondria as Well as Cytosol, and Is Accompanied by Intensified Mitochondrial O2 Consumption and ROS Release"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2539"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Cells"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Festerling, Karina"],["dc.contributor.author","Can, Karolina"],["dc.contributor.author","Kügler, Sebastian"],["dc.contributor.author","Müller, Michael"],["dc.date.accessioned","2021-04-14T08:26:49Z"],["dc.date.available","2021-04-14T08:26:49Z"],["dc.date.issued","2020"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.3390/cells9122539"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17668"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82087"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","MDPI"],["dc.relation.eissn","2073-4409"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Overshooting Subcellular Redox-Responses in Rett-Mouse Hippocampus during Neurotransmitter Stimulation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","959"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Biochemical Society Transactions"],["dc.bibliographiccitation.lastpage","964"],["dc.bibliographiccitation.volume","42"],["dc.contributor.author","Müller, Michael"],["dc.contributor.author","Can, Karolina"],["dc.date.accessioned","2018-09-28T10:11:26Z"],["dc.date.available","2018-09-28T10:11:26Z"],["dc.date.issued","2014"],["dc.description.abstract","RTT (Rett syndrome) is a severe progressive neurodevelopmental disorder with a monogenetic cause, but complex and multifaceted clinical appearance. Compelling evidence suggests that mitochondrial alterations and aberrant redox homoeostasis result in oxidative challenge. Yet, compared with other severe neuropathologies, RTT is not associated with marked neurodegeneration, but rather a chemical imbalance and miscommunication of neuronal elements. Different pharmacotherapies mediate partial improvement of conditions in RTT, and also antioxidants or compounds improving mitochondrial function may be of potential merit. In the present paper, we summarize findings from patients and transgenic mice that point towards the nature of RTT as a mitochondrial disease. Also, open questions are addressed that require clarification to fully understand and successfully target the associated cellular redox imbalance."],["dc.identifier.doi","10.1042/BST20140071"],["dc.identifier.pmid","25109986"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15853"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1470-8752"],["dc.title","Aberrant redox homoeostasis and mitochondrial dysfunction in Rett syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","3064016"],["dc.bibliographiccitation.journal","Oxidative Medicine and Cellular Longevity"],["dc.bibliographiccitation.volume","2017"],["dc.contributor.author","Bebensee, Dörthe F."],["dc.contributor.author","Can, Karolina"],["dc.contributor.author","Müller, Michael"],["dc.date.accessioned","2018-09-28T09:44:52Z"],["dc.date.available","2018-09-28T09:44:52Z"],["dc.date.issued","2017"],["dc.description.abstract","Rett syndrome (RTT) is a neurodevelopmental disorder with mutations in the MECP2 gene. Mostly girls are affected, and an apparently normal development is followed by cognitive impairment, motor dysfunction, epilepsy, and irregular breathing. Various indications suggest mitochondrial dysfunction. In Rett mice, brain ATP levels are reduced, mitochondria are leaking protons, and respiratory complexes are dysregulated. Furthermore, we found in MeCP2-deficient mouse (Mecp2-/y ) hippocampus an intensified mitochondrial metabolism and ROS generation. We now used emission ratiometric 2-photon imaging to assess mitochondrial morphology, mass, and membrane potential (ΔΨm) in Mecp2-/y hippocampal astrocytes. Cultured astrocytes were labeled with the ΔΨm marker JC-1, and semiautomated analyses yielded the number of mitochondria per cell, their morphology, and ΔΨm. Mecp2-/y astrocytes contained more mitochondria than wild-type (WT) cells and were more oxidized. Mitochondrial size, ΔΨm, and vulnerability to pharmacological challenge did not differ. The antioxidant Trolox opposed the oxidative burden and decreased the mitochondrial mass, thereby dampening the differences among WT and Mecp2-/y astrocytes; mitochondrial size and ΔΨm were not markedly affected. In conclusion, mitochondrial alterations and redox imbalance in RTT also involve astrocytes. Mitochondria are more numerous in Mecp2-/y than in WT astrocytes. As this genotypic difference is abolished by Trolox, it seems linked to the oxidative stress in RTT."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1155/2017/3064016"],["dc.identifier.pmid","28894505"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14620"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15846"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.eissn","1942-0994"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Increased Mitochondrial Mass and Cytosolic Redox Imbalance in Hippocampal Astrocytes of a Mouse Model of Rett Syndrome: Subcellular Changes Revealed by Ratiometric Imaging of JC-1 and roGFP1 Fluorescence"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","227"],["dc.bibliographiccitation.journal","Free Radical Biology & Medicine"],["dc.bibliographiccitation.lastpage","241"],["dc.bibliographiccitation.volume","76"],["dc.contributor.author","Weller, Jonathan"],["dc.contributor.author","Kizina, Kathrin M."],["dc.contributor.author","Can, Karolina"],["dc.contributor.author","Bao, Guobin"],["dc.contributor.author","Müller, Michael"],["dc.date.accessioned","2018-09-28T09:56:42Z"],["dc.date.available","2018-09-28T09:56:42Z"],["dc.date.issued","2014"],["dc.description.abstract","Reactive oxygen species mediate cellular signaling and neuropathologies. Hence, there is tremendous interest in monitoring (sub)cellular redox conditions. We evaluated the genetically engineered redox sensor HyPer in mouse hippocampal cell cultures. Two days after lipofection, neurons and glia showed sufficient expression levels, and H2O2 reversibly and dose-dependently increased the fluorescence ratio of cytosolic HyPer. Yet, repeated H2O2 treatment caused progressively declining responses, and with millimolar doses an apparent recovery started while H2O2 was still present. Although HyPer should be H2O2 specific, it seemingly responded also to other oxidants and altered cell-endogenous superoxide production. Control experiments with the SypHer pH sensor confirmed that the HyPer ratio responds to pH changes, decreasing with acidosis and increasing during alkalosis. Anoxia/reoxygenation evoked biphasic HyPer responses reporting apparent reduction/oxidation; replacing Cl(-) exerted only negligible effects. Mitochondria-targeted HyPer readily responded to H2O2-albeit less intensely than cytosolic HyPer. With ratiometric two-photon excitation, H2O2 increased the cytosolic HyPer ratio. Time-correlated fluorescence-lifetime imaging microscopy (FLIM) revealed a monoexponential decay of HyPer fluorescence, and H2O2 decreased fluorescence lifetimes. Dithiothreitol failed to further reduce HyPer or to induce reasonable FLIM and two-photon responses. By enabling dynamic recordings, HyPer is superior to synthetic redox-sensitive dyes. Its feasibility for two-photon excitation also enables studies in more complex preparations. Based on FLIM, quantitative analyses might be possible independent of switching excitation wavelengths. Yet, because of its pronounced pH sensitivity, adaptation to repeated oxidation, and insensitivity to reducing stimuli, HyPer responses have to be interpreted carefully. For reliable data, side-by-side pH monitoring with SypHer is essential."],["dc.identifier.doi","10.1016/j.freeradbiomed.2014.07.045"],["dc.identifier.pmid","25179473"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15849"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1873-4596"],["dc.title","Response properties of the genetically encoded optical H2O2 sensor HyPer"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]