Adaptive responses to the stress induced by hyperthermia or hydrogen peroxide in human fibroblasts.

摘要: Perturbation of oxidant/antioxidant cellular balance, induced by metabolism and exogenous sources, causes deleterious effects to proteins, lipids, nucleic acids, leading a condition named “oxidative stress” that is involved in several diseases, such as cancer, ischemia-reperfusion injury, neurodegenerative disorders. Among the agents, both H2O2 hyperthermia have been implicated oxidative stress promotion linked with activation apoptotic or necrotic mechanisms cell death. The goal this work was better understand involvement some stress-related proteins adaptive responses mounted human fibroblasts versus differently 42°C H2O2. research developed, switching off inducible nitric oxide synthase (iNOS) expression through antisense oligonucleotide transfection studying possible coregulation HSP32 (also HO-1), HSP70, iNOS their induction DNA damage. Several biochemical parameters, viability (MTT assay), membrane integrity (lactate dehydrogenase release), reactive oxygen species formation, glutathione levels, immunocytochemistry analysis iNOS, HO-1 genomic fragmentation (HALO/COMET transmembrane mitochondrial potential () were examined. Cells collected immediately at end stress-inducing treatment. results, confirming pleiotropic function i-NOS, indicate that: (i) HO-1/HSP32, are finely tuned contribute all together, fibroblasts, ameliorating resistance damage; (ii) ROS exposure, least hyperthermia, contributes growth arrest more than apoptosis activation; (iii) dysfunction, presence inhibition seems be clearly death after treatment, but not hyperthermia. Exp Biol Med 228:491–498, 2003