Biology subjects

Kulkoviene, G.

Publications and source records attributed to Kulkoviene, G..

3 recordsLinked to original sources

bioRxiv2024

Psoriasis-like inflammation induces mitochondrial function and structure changes in human keratinocytes and fibroblasts

Mitochondrial structural and functional changes accompany psoriasis, yet the mitochondrial response to psoriatic inflammation in keratinocytes and fibroblasts remains unexplored. In this study, we investigated the effect of psoriasis-like inflammation (PLI) induced by a cytokine cocktail (interleukin (IL)-17A, IL-22 and tumour necrosis factor (TNF)-) on mitochondrial network morphology and function in cultured keratinocytes (HaCaT) and fibroblasts (BJ-5ta). In both cell types, PLI triggered expression of psoriasis-related Elafin and high amounts of cytokines (IL-1, IL-6), interferons (IFN-, IFN-{beta}, IFN-{gamma}) and chemokines (C-C motif chemokine 5 (CCL5) and IL-8), accompanied by increased mitochondrial membrane potential, reactive oxygen species (ROS) production, respiration suppression, network fragmentation, swelling, and cristae disassembly. Stimulated emission depletion (STED) nanoscopy revealed the disappearance of mitochondrial cristae in response to PLI, with the process starting more quickly and being more pronounced in keratinocytes than in fibroblasts. These findings highlight cell-specific mitochondrial responses to psoriatic inflammation, guiding future investigations towards new pharmacological targets for managing psoriasis. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=197 SRC="FIGDIR/small/611357v2_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@153d89org.highwire.dtl.DTLVardef@7b26dcorg.highwire.dtl.DTLVardef@13436c9org.highwire.dtl.DTLVardef@f8f900_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2024

Astrocyte Contribution to Brain State-Dependent Neurovascular Coupling

Neurovascular coupling (NVC) ensures sufficient and targeted blood flow during increased neuronal activity. Astrocytic participation in NVC has long been debated, likely due to the intricacy of the intracellular Ca2+ fluxes and the diversity of their regulatory capacities. As astrocyte signaling changes with brain states, we focused on their involvement in voluntary sensing in freely behaving mice. We used 2-photon microscopy to record cellular and vascular activity in the whisker barrel cortex of awake head-fixed animals. The NVC initiated by volitional whisking in the resting mouse was compared to the whisking preceding locomotion and experimenter-evoked whisker deflections. We developed an analysis method to detect early, subcellular astrocytic activity and found it corresponded with neuronal and vascular responses under all three conditions. After the depletion of noradrenaline (NA), the early astrocytic Ca2+ response to volitional whisking was only moderately reduced and primarily in astrocytic processes closest to the blood vessels. Meanwhile, the dilation of 1st order capillaries was also reduced. Together, these findings demonstrate significant disruptions in the focal regulation of cerebral blood flow, potentially limiting the sustenance of activated neurons. This disruption appeared to translate into behavioral aberrations, as NA-depleted mice exhibited an extended period of exploratory whisking prior to locomotion. Remarkably, NA-depletion did not alter cellular or blood flow responses to locomotion or experimenter-evoked whisking. Our study confirms an astrocytic contribution to NVC, which is relevant during volitional sensing. It also suggests that self-directed sensory processing depends on an appropriate NVC response, which itself depends on NA and astrocyte activity.

neuroscience↗

bioRxiv2023

Comparison of mitochondrial response to SARS-CoV-2 spike protein receptor binding domain in human lung microvascular, coronary artery endothelial and bronchial epithelial cells

Recent evidence indicate that SARS-CoV-2 spike protein affects mitochondria with a cell type-dependent outcome. We elucidate the effect of SARS-CoV-2 receptor binding domain (RBD) on the mitochondrial network and cristae morphology, oxygen consumption, mitoROS production, and inflammatory cytokine expression in cultured human lung microvascular (HLMVEC) and coronary artery endothelial (HCAEC) and bronchial epithelial cells (HBEC). Live Mito Orange staining, STED microscopy and Fiji MiNa analysis were used for mitochondrial cristae and network morphometry, Agilent XFp analyser for mitochondrial/glycolytic activity, MitoSOX fluorescence for mitochondrial ROS, and qRT-PCR plus Luminex for cytokines. In HLMVEC, SARS-CoV-2 RBD fragmented the mitochondrial network, decreased cristae density, mitochondrial oxygen consumption and glycolysis and induced mitoROS-mediated GM-CSF and IL-1{beta} expression in all three investigated cell types and IL-8 - in both endothelial cell types. Mitochondrial ROS control SARS-CoV-2 RBD-induced inflammation in HLMVEC, HCAEC and HBEC, with the mitochondria of HLMVEC being more sensitive to SARS-CoV-2 RBD.

immunology↗