RESUMO
Both elevated iron concentrations and the resulting oxidative stress condition are common signs in retinas of patients with age-related macular degeneration (AMD). The role of phospholipase A(2) (PLA(2)) during iron-induced retinal toxicity was investigated. To this end, isolated retinas were exposed to increasing Fe(2+) concentrations (25, 200 or 800 µM) or to the vehicle, and lipid peroxidation levels, mitochondrial function, and the activities of cytosolic PLA(2) (cPLA(2)) and calcium-independent PLA(2) (iPLA(2)) were studied. Incubation with Fe(2+) led to a time- and concentration-dependent increase in retinal lipid peroxidation levels whereas retinal cell viability was only affected after 60 min of oxidative injury. A differential release of arachidonic acid (AA) and palmitic acid (PAL) catalyzed by cPLA(2) and iPLA(2) activities, respectively, was also observed in microsomal and cytosolic fractions obtained from retinas incubated with iron. AA release diminished as the association of cyclooxygenase-2 increased in microsomes from retinas exposed to iron. Retinal lipid peroxidation and cell viability were also analyzed in the presence of cPLA(2) inhibitor, arachidonoyl trifluoromethyl ketone (ATK), and in the presence of iPLA(2) inhibitor, bromoenol lactone (BEL). ATK decreased lipid peroxidation levels and also ERK1/2 activation without affecting cell viability. BEL showed the opposite effect on lipid peroxidation. Our results demonstrate that iPLA(2) and cPLA(2) are differentially regulated and that they selectively participate in retinal signaling in an experimental model resembling AMD.
Assuntos
Compostos Ferrosos/toxicidade , Degeneração Macular/induzido quimicamente , Degeneração Macular/enzimologia , Fosfolipases A2/metabolismo , Retina/enzimologia , Animais , Bovinos , Isoenzimas/metabolismo , Isoenzimas/fisiologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Técnicas de Cultura de Órgãos , Fosfolipases A2/fisiologiaRESUMO
OBJECTIVE: To investigate the role of oxidant/antioxidant status and protein oxidation in the development of age-related macular degeneration. METHOD: The activities of serum superoxide dismutase and glutathione peroxidase and the levels of serum malondialdehyde, advanced oxidation protein products, glutathione and vitamin C were measured in 25 patients with age-related macular degeneration and 25 control subjects without age-related macular degeneration. RESULT: The malondialdehyde and advanced oxidation protein product levels in the serum were significantly higher in the age-related macular degeneration patient group than in the control group (p<0.05). The superoxide dismutase activity in the serum was significantly lower in the age-related macular degeneration patient group than in the control group (p<0.05). The levels of vitamin C and glutathione and the activity of glutathione peroxidase in the serum were unchanged between groups (p>0.05). CONCLUSION: The results of the present study suggest that decreased effectiveness of the antioxidant defense system and increased oxidative stress may play a role in the pathogenesis of age-related macular degeneration.
Assuntos
Neovascularização de Coroide/etiologia , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/fisiologia , Degeneração Macular/etiologia , Estresse Oxidativo/fisiologia , Superóxido Dismutase/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Biomarcadores/metabolismo , Estudos de Casos e Controles , Neovascularização de Coroide/metabolismo , Feminino , Glutationa Peroxidase/análise , Humanos , Degeneração Macular/enzimologia , Degeneração Macular/metabolismo , Masculino , Pessoa de Meia-Idade , Superóxido Dismutase/análiseRESUMO
OBJECTIVE: To investigate the role of oxidant/antioxidant status and protein oxidation in the development of age-related macular degeneration. METHOD: The activities of serum superoxide dismutase and glutathione peroxidase and the levels of serum malondialdehyde, advanced oxidation protein products, glutathione and vitamin C were measured in 25 patients with age-related macular degeneration and 25 control subjects without age-related macular degeneration. RESULT: The malondialdehyde and advanced oxidation protein product levels in the serum were significantly higher in the age-related macular degeneration patient group than in the control group (p<0.05). The superoxide dismutase activity in the serum was significantly lower in the age-related macular degeneration patient group than in the control group (p<0.05). The levels of vitamin C and glutathione and the activity of glutathione peroxidase in the serum were unchanged between groups (p>0.05). CONCLUSION: The results of the present study suggest that decreased effectiveness of the antioxidant defense system and increased oxidative stress may play a role in the pathogenesis of age-related macular degeneration.