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Background: The expression of aquaporin 4 (AQP4) and intermediate filament (IF) proteins is altered in malignant glioblastoma (GBM), yet the expression of the major IF-based cytolinker, plectin (PLEC), and its contribution to GBM migration and invasiveness, are unknown. Here, we assessed the contribution of plectin in affecting the distribution of plasmalemmal AQP4 aggregates, migratory properties, and regulation of cell volume in astrocytes., Methods: In human GBM, the expression of glial fibrillary acidic protein (GFAP), AQP4 and PLEC transcripts was analyzed using publicly available datasets, and the colocalization of PLEC with AQP4 and with GFAP was determined by immunohistochemistry. We performed experiments on wild-type and plectin-deficient primary and immortalized mouse astrocytes, human astrocytes and permanent cell lines (U-251 MG and T98G) derived from a human malignant GBM. The expression of plectin isoforms in mouse astrocytes was assessed by quantitative real-time PCR. Transfection, immunolabeling and confocal microscopy were used to assess plectin-induced alterations in the distribution of the cytoskeleton, the influence of plectin and its isoforms on the abundance and size of plasmalemmal AQP4 aggregates, and the presence of plectin at the plasma membrane. The release of plectin from cells was measured by ELISA. The migration and dynamics of cell volume regulation of immortalized astrocytes were assessed by the wound-healing assay and calcein labeling, respectively., Results: A positive correlation was found between plectin and AQP4 at the level of gene expression and protein localization in tumorous brain samples. Deficiency of plectin led to a decrease in the abundance and size of plasmalemmal AQP4 aggregates and altered distribution and bundling of the cytoskeleton. Astrocytes predominantly expressed P1c, P1e, and P1g plectin isoforms. The predominant plectin isoform associated with plasmalemmal AQP4 aggregates was P1c, which also affected the mobility of astrocytes most prominently. In the absence of plectin, the collective migration of astrocytes was impaired and the dynamics of cytoplasmic volume changes in peripheral cell regions decreased. Plectin's abundance on the plasma membrane surface and its release from cells were increased in the GBM cell lines., Conclusions: Plectin affects cellular properties that contribute to the pathology of GBM. The observed increase in both cell surface and released plectin levels represents a potential biomarker and therapeutic target in the diagnostics and treatment of GBMs., (© 2024. The Author(s).)

Axonal swellings (AS) are one of the neuropathological hallmark of axonal injury in several disorders from trauma to neurodegeneration. Current evidence proposes a role of perturbed Ca 2+ homeostasis in AS formation, involving impaired axonal transport and focal distension of the axons. Mechanisms of AS formation, in particular moments following injury, however, remain unknown. Here we show that AS form independently from intra-axonal Ca 2+ changes, which are required primarily for the persistence of AS in time. We further show that the majority of axonal proteins undergoing de/phosphorylation immediately following injury belong to the cytoskeleton. This correlates with an increase in the distance of the actin/spectrin periodic rings and with microtubule tracks remodeling within AS. Observed cytoskeletal rearrangements support axonal transport without major interruptions. Our results demonstrate that the earliest axonal response to injury consists in physiological adaptations of axonal structure to preserve function rather than in immediate pathological events signaling axonal destruction., (© 2022. The Author(s).)

Background: The term arterial stiffness (ArSt) describes structural changes in arterial wall related to the loss of elasticity and is known as an independent predictor of cardiovascular diseases (CVD). The evidence relating to ArSt and triglycerides (TG) shows contradictory results. This paper means to survey the association between high TG and ArSt, utilizing the cardio-ankle vascular index (CAVI)., Methods: Subjects aged between 25 and 64 years from a random population-based sample were evaluated between 2013 and 2016. Data from questionnaires, blood pressure, anthropometric measures, and blood samples were collected and analyzed. CAVI was measured using VaSera VS-1500 N devise. Subjects with a history of CVD or chronic renal disease were excluded., Results: One thousand nine hundred thirty-four participants, 44.7% of males, were included. The median age was 48 (Interquartile Range [IQR] 19) years, TG levels were 1.05 (0.793) mmol/L, and CAVI 7.24 (1.43) points. Prevalence of high CAVI was 10.0% (14.5% in males and 6.4% in females; P <  0.001) and prevalence of hypertriglyceridemia was 20.2% (29.2% in males and 13% in females, P <  0.001). The correlation between TG and CAVI was 0.136 (P <  0.001). High CAVI values were more prevalent among participants with metabolic syndrome (MetS), high blood pressure, dysglycemia, abdominal obesity, high LDL-cholesterol (LDL-c), and high total cholesterol. Using binary regression analysis, high TG were associated with high CAVI, even after adjustment for other MetS components, age, gender, smoking status, LDL-c, and statin treatment (β = 0.474, OR = 1.607, 95% CI = 1.063-2.429, P = 0.024)., Conclusion: TG levels were correlated with ArSt, measured as CAVI. High TG was associated with high CAVI independent of multiple cardiometabolic risk factors. Awareness of the risks and targeted treatment of hypertriglyceridemia could further benefit in reducing the prevalence of CVD and events.