Endothelial cell-oligodendrocyte interactions in small vessel disease and aging

Cerebral small vessel disease (SVD) is a prevalent, neurological disease that significantly increases the risk of stroke and dementia. The main pathological changes are vascular, in the form of lipohyalinosis and arteriosclerosis, and in the white matter (WM), in the form of WM lesions. Despite this, it is unclear to what extent the key cell types involved–the endothelial cells (ECs) of the vasculature and the oligodendrocytes of the WM–interact. Here, we describe the work that has so far been carried out suggesting an interaction between ECs and oligodendrocytes in SVD. As these interactions have been studied in more detail in other disease states and in development, we explore these systems and discuss the role these mechanisms may play in SVD

Stereoselective Construction of 2,7-Disubstituted <i>fused</i>-Bis Tetrahydrofuran Skeletons: Biomimetic-Type Synthesis and Biological Evaluation of (±)- and (−)-Aplysiallene and Their Derivatives

A series of <i>trans</i>/<i>trans</i> and <i>cis</i>/<i>cis</i> <i>fused</i>-bis tetrahydrofuran compounds have been obtained stereoselectively in high yields via a one-pot operation involving the intramolecular haloetherification of (<i>Z</i>,<i>Z</i>)-diene diol <b>19a</b> and (<i>E</i>,<i>E</i>)-diene disilylether <b>19d</b>, respectively. This method was subsequently applied to the biomimetic-type synthesis of (±)- and (−)-aplysiallene. The inhibitory activities of these compounds and their bromodiene isomers toward Na⁺/K⁺ ATPase were determined in vitro, and gave IC₅₀ values of approximately 15 μM in all cases

Apoptosis-Mediated Cytotoxicity of Prodigiosin-Like Red Pigment Produced by γ-Proteobacterium and Its Multiple Bioactivities

Recently we discovered a bacterial strain (MS-02-063) that produces large amounts of red pigment (PG-L-1). Among the cell lines tested, U937 cells showed the highest susceptibility to PG-L-1 toxicity. PG-L-1 induced typical apoptotic nuclear morphological changes, and single cell gel electrophoresis revealed that PG-L-1 caused DNA fragmentation in U937 cells. In PG-L-1 treated U937 cells, the acidic compartment such as lysosomes disappeared, suggesting that PG-L-1-induced disorder of intracellular pH compartmentalization might trigger apoptotic signal. Since p38 MAP kinase inhibitor specifically prevented the PG-L-1 mediated cell death, p38 MAP kinase may be involved in the cytotoxic mechanism. In fact, immunoblot analysis of p38 MAP kinase revealed that phosphorylation of p38 MAP kinase occurred in PG-L-1-treated U937 cells. In addition to the activity to induce apoptotic cell death as reported in several PG family members, our chemiluminescence analysis suggested that PG-L-1 inhibited superoxide generation by 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated U937 cells in a dose-dependent manner. Since PG-L-1 had no effect on the chemiluminescence response caused by xanthine oxidase/hypoxanthine system, PG-L-1 acts on the enzyme system responsible for O_2- generation rather than direct scavenging toward O_2-. Our results suggest that PG-L-1 causes multiple biochemical effects on the target cells such as increase in pH in acidic intracellular compartment, activation of p38 MAP kinase, inhibition of O_2- generation, and eventually induces apoptotic cell death