Peroxisomal participation in the cellular response to the oxidative stress of endotoxin

Abstract

Exposure to a sublethal dose of endotoxin offers protection against subsequent oxidative stresses. The cellular mechanisms involved in generating this effect are not well understood. We evaluated the effect of endotoxin on antioxidant enzymes in liver peroxisomes. Peroxisomes have recently been shown to contain superoxide dismutase (SOD) and glutathione peroxidase (GPX) in addition to catalase. Peroxisomes were isolated from liver homogenates by differential and density gradient centrifugations. Endotoxin treatment increased the specific activity of SOD and GPX in peroxisomes to 208% and 175% of control activity, respectively. These findings correlated with increases in peroxisomal SOD and GPX proteins observed by immunoblot. Although the quantity of catalase protein was increased when assessed by immunoblot analysis, the specific activity of catalase was decreased to 68% of control activity. Activation of catalase with ethanol only restored catalase activity to control levels suggesting that catalase had undergone irreversible inactivation. The observed increase in GPX activity may represent a compensatory mechanism triggered by accumulating H2O2. The data presented here suggest for the first time that mammalian peroxisomal antioxidant enzymes are altered during the oxidative injury of endotoxin treatment.

Induction of Tubular Peroxisomes by UV Irradiation and Reactive Oxygen Species in HepG2 Cells

“…Their results in the model of renal ischemia and reperfusion of rat kidney indicate that, despite cell damage due to ROS, the peroxisomal compartment exhibits signs of regeneration (Singh and Gulati 1995) similar to the response observed in regenerating rat liver (Lüers et al 1993). Along the same line, the oxidative stress induced by endotoxin treatment in rat liver caused a significant elevation of the antioxidative peroxisomal enzymes SOD and glutathione peroxidase (Dhaunsi et al 1993). In cultured skin fibroblasts, Kremser et al (1995) compared the sensitivity of the peroxisomal lipid ␤-oxidation system to ROS with that of the mitochondrial system and noted that peroxisomes were more sensitive than mitochondria.…”

Endotoxin induces structure-function alterations of rat liver peroxisomes: Kupffer cells released factors as possible modulators

“…22,23 Moreover, modulation of peroxisomal enzymes (catalase, glutathione peroxidase, CuZn superoxide dismutase, and Mn superoxide dismutase) related with oxidative stress, 24 suggests a role for this organelle in LPS-associated acute phase response. 7,39 Therefore, understanding the effects of LPS/cytokines on the structure/ function of peroxisomes is important to delineate the role of peroxisomes in the pathophysiology of LPS-induced organ failure and other peroxisomal disorders associated with increased levels of TNF-␣ and other proinflammatory cytokines.…”

“…20 TNF-␣ and LPS also modulate the activities of antioxidant enzymes and the enzyme system for fatty acid oxidation in peroxisomes in liver. [21][22][23][24] This down-regulation of peroxisomal ␤-oxidation may contribute to the increased pool of fatty acids for the synthesis of triglycerides. The increased levels of cholesterol are the result of the observed increase in levels of HMG-CoA reductase and increased synthesis of cholesterol.…”

Glucuronic Acid-conjugated Dihydroxy Fatty Acids in the Urine of Patients with Generalized Peroxisomal Disorders

“…Mechanisms in peroxisomes counteract the production of these reactive oxygen species by enzymes catalyzing the conversion of the superoxide radical ion (O 2 . ) to hydrogen peroxide and then to H 2 O and O 2 (48). Failure to form the intact peroxisome in disorders of peroxisomal biogenesis may perturb the balance of formation and catabolism of these reactive oxygen species and lead to lipid peroxidation.…”