ABSTRACT
Cholesterol suppresses the hemolysis and the detachment of cytoskeletal proteins from bilayer in the human erythrocyte membrane under stress conditions. However, there is little information on how cholesterol functions. So, examining the role of a short side chain of cholesterol, we used the plant sterols such as ß-sitosterol and stigmasterol. Incorporation of sterols into the membrane using a sterol/methyl-ß-cyclodextrin complex was confirmed by the mass spectrometry. Hemolysis of human erythrocytes under high hydrostatic pressure (200 MPa) or hypotonic conditions was suppressed by cholesterol, but not by ß-sitosterol and stigmasterol. Moreover, the bilayer-cytoskeleton interaction was also strengthened by cholesterol, but not by ß-sitosterol and stigmasterol. Taken together, we suggest that the short side chain of cholesterol plays an important role in the membrane stability of human erythrocytes.
Subject(s)
Cell Membrane/drug effects , Erythrocytes/drug effects , Sitosterols/pharmacology , Stigmasterol/pharmacology , beta-Cyclodextrins/pharmacology , Cells, Cultured , Cholesterol/pharmacology , Cytoskeletal Proteins/metabolism , Cytoskeleton/drug effects , Erythrocytes/metabolism , Hemolysis/drug effects , HumansABSTRACT
Hydrogen sulfide (H2S), the third gasotransmitter, is endogenously generated by certain H2S synthesizing enzymes, including cystathionine-γ-lyase (CSE) and cystathionine-ß-synthase (CBS) from L-cysteine in the mammalian body. Several studies have shown that endogenous and exogenous H2S affects the proliferation of cancer cells, although the effects of H2S appear to vary with cell type, being either promotive or suppressive. In the present study, we determined whether endogenously formed H2S regulates proliferation in human gastric cancer AGS cells. CSE, but not CBS, was expressed in AGS cells. CSE inhibitors, DL-propargylglycine (PPG) and ß-cyano-L-alanine (BCA), significantly suppressed the proliferation of AGS cells in a concentration-dependent manner. CSE inhibitors did not increase lactate dehydrogenase (LDH) release in the same concentration range. The inhibitory effects of PPG and BCA on cell proliferation were reversed by repetitive application of NaHS, a donor of H2S. Interestingly, nuclear condensation and fragmentation were detected in AGS cells treated with PPG or BCA. These results suggest that endogenous H2S produced by CSE may contribute to the proliferation of gastric cancer AGS cells, most probably through anti-apoptotic actions.
