Geranylgeranylacetone protects human monocytes from mitochondrial membrane depolarization independently of Hsp70 expression.
The anti-ulcer drug geranylgeranylacetone (GGA) has been shown to induce the expression of heat shock proteins (HSPs), in particular of Hsp70, in gastric and small intestine cells. In this study, we investigated whether GGA was able to induce Hsp70 in another cell type, human monocytes, which represent a well-established model of Hsp70 expression under oxidative stress. In these cells, GGA had no significant effect either on basal or tobacco smoke-induced Hsp70 expression. We further investigated the effects of GGA on mitochondria, a key organelle of oxidant-mediated cell injury and a putative target for GGA-mediated protection. GGA significantly increased basal mitochondrial membrane polarization and inhibited the decrease in mitochondrial membrane potential of human monocytes exposed to distinct sources of clinically relevant oxidants such as tobacco smoke and y-irradiation. Our results indicate that mitochondria are targets for GGA-mediated protection against oxidative stress in human monocytes, independently of Hsp70.
Aron
Y
Y
Laboratoire de Physiologie Respiratoire, Groupe Hospitalier et Universitaire Cochin-Port Royal, Université Paris V, France.
Vayssier-Taussat
M
M
Bachelet
M
M
Polla
B S
BS
D000897:Anti-Ulcer Agents / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D004224:Diterpenes / Q000737:chemistry* / Q000494:pharmacology*; D005434:Flow Cytometry; D005720:Gamma Rays; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D008928:Mitochondria / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000528:radiation effects; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D013997:Time Factors
D000897:Anti-Ulcer Agents; D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D017382:Reactive Oxygen Species; C031049:geranylgeranylacetone