Biology subjects

Voloviceva, E.

Publications and source records attributed to Voloviceva, E..

3 recordsLinked to original sources

bioRxiv2026

The protein and lipid compositions of brain apolipoprotein E particles are cell type-specific

Genetic variation in APOE, which encodes a lipid transporter apolipoprotein E (apoE), is the strongest risk factor for late-onset Alzheimer's disease (AD). Although central nervous system (CNS) apoE is produced by various cell types, including astrocytes, microglia, and pericytes, it is unclear whether apoE lipoproteins are a homogeneous population or if their molecular composition varies depending on their cellular origin. Emerging evidence suggests that CNS apoE lipoproteins contribute to AD-related processes, including amyloid deposition, neuroinflammation, synaptic maintenance, and blood-brain barrier function in a cell type-specific manner. We hypothesized that the compositions of CNS apoE lipoproteins depend on their cellular origin and investigated the lipid and protein profiles of apoE particles secreted by induced pluripotent stem cell (iPSC)-derived brain cells and derived from human cerebrospinal fluid (CSF) using liquid chromatography-mass spectrometry (LC-MS/MS). Our results demonstrate that astrocytes, pericytes, and microglia secrete apoE lipoproteins with distinct, cell type-specific lipid and protein profiles. Astrocyte-secreted particles were enriched in sphingomyelins and proteins linked to lipid metabolism, whereas pericyte-secreted particles contained ether-linked phospholipids and proteins associated with antioxidant activity. The lipidation of microglial apoE was markedly lower, but these particles had higher levels of transferrin, apoC-II, and cathepsin D. Notably, one-third of identified features were cell type-specific, highlighting the substantial molecular specialization across cell types. Most lipids and proteins identified in cell-secreted apoE were also detected in CSF-derived particles. Our findings advance the understanding of apoE biology by shifting the focus from apoE as a single, homogeneous entity to a diverse population of complex particles, the composition of which might be linked to functions in health and neurodegenerative diseases.

neuroscience↗

bioRxiv2024

Metformin treatment results in distinctive skeletal muscle mitochondrial remodeling in rats with different intrinsic aerobic capacities

The rationale for the use of metformin as a treatment to slow aging was largely based on data collected from metabolically unhealthy individuals. For healthspan extension metformin will also be used in periods of good health. To understand potential context specificity of metformin treatment on skeletal muscle, we used a rat model (HCR/LCR) with a divide in intrinsic aerobic capacity. Outcomes of metformin treatment differed based on baseline intrinsic mitochondrial function, oxidative capacity of the muscle (gastroc vs soleus), and the mitochondrial population (IMF vs SS). Metformin caused lower ADP-stimulated respiration in LCRs, with less of a change in HCRs. However, a washout of metformin resulted in an unexpected doubling of respiratory capacity in HCRs. These improvements in respiratory capacity were accompanied by mitochondrial remodeling that included increases in protein synthesis and changes in morphology. Our findings raise questions about whether the positive findings of metformin treatment are broadly applicable.

physiology↗

bioRxiv2022

Skeletal muscle nuclei in mice are not post-mitotic

The skeletal muscle research field generally accepts that nuclei in skeletal muscle fibers (i.e., myonuclei) are post-mitotic and unable to proliferate. Because our deuterium oxide (D2O) labeling studies showed DNA synthesis in skeletal muscle tissue, we hypothesized that resident myonuclei can replicate in vivo. To test this hypothesis, we used a mouse model that temporally labeled myonuclei with GFP followed by D2O labeling during normal cage activity, functional overload, and with satellite cell ablation. During normal cage activity, we observed deuterium enrichment into myonuclear DNA in 7 out of 7 plantaris (PLA), 6 out of 6 tibialis anterior (TA), 5 out of 7 gastrocnemius (GAST) and 7 out of 7 quadriceps (QUAD). The average fractional synthesis rates (FSR) of DNA in myonuclei were: 0.0202 {+/-} 0.0093 in PLA, 0.0239 {+/-} 0.0040 in TA, 0.0076 {+/-} 0. 0058 in GAST, and 0.0138 {+/-} 0.0039 in QUAD, while there was no replication in myonuclei from EDL. These FSR values were largely reproduced in the overload and satellite cell ablation conditions although there were higher synthesis rates in the overloaded PLA muscle. We further provided evidence that myonuclear replication is through endoreplication that results in polyploidy. These novel findings contradict the dogma that skeletal muscle nuclei are post-mitotic and open potential avenues to harness the intrinsic replicative ability of myonuclei for muscle maintenance and growth. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/513426v2_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@1e4d210org.highwire.dtl.DTLVardef@19b52daorg.highwire.dtl.DTLVardef@5c9a53org.highwire.dtl.DTLVardef@197dc0d_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗