Immunological evidence for increased oxidative stress in diabetic rats

Traverso, Nicola; Menini, Stefano; Cosso, L.; Odetti, Patrizio; Albano, Emanuele; Pronzato, Maria Adelaide; Marinari, Umberto M.

doi:10.1007/s001250050902

Cited by 67 publications

(34 citation statements)

References 35 publications

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“…This is supported by the apparent relationship between diabetes and elevated oxidative stress and by the reported ability of various agents possessing different antioxidant characteristics to ameliorate many of the glomerular abnormalities associated with diabetes (28)(29)(30). Altered levels of circulating antioxidants (28,31), intracellular scavenging enzymes (32,33), and increased amounts of oxidatively modified cellular components (12,30,31) have been used as indicators of an oxidative stress imbalance in diabetes. In the present protocol, we examined 2 indexes that have previously been used as measures of oxidative stress, namely CuZnSOD gene expression and TBARS content.…”

Section: Discussionmentioning

confidence: 97%

“…Experimental studies of cultured glomerular cells have clearly demonstrated that hyperglycemia itself can initiate a series of cellular changes that characterize progression to glomerulosclerosis (7)(8)(9); today, there are numerous hypotheses that may account for this phenomenon (10). Among currently debated theories, a potential role for oxidative stress has been identified as an early initiating mechanism by which the high-glucose environment may lead to cellular injury in diabetes (11,12).…”

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confidence: 99%

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Combined antioxidant and COMT inhibitor treatment reverses renal abnormalities in diabetic rats.

et al. 2000

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The development and progression of diabetic nephropathy is dependent on glucose homeostasis and many other contributing factors. In the present study, we examined the effect of nitecapone, an inhibitor of the dopaminemetabolizing enzyme catechol-O-methyl transferase (COMT) and a potent antioxidant, on functional and cellular determinants of renal function in rats with streptozotocin-induced diabetes. Administration of nitecapone to diabetic rats normalized urinary sodium excretion in a manner consistent with the dopaminedependent inhibition of proximal tubule Na,K-ATPase activity. Hyperfiltration, focal glomerulosclerosis, and albuminuria were also reversed by nitecapone, but in a manner that is more readily attributed to the antioxidant potential of the agent. A pattern of elevated oxidative stress, measured as CuZn superoxide dismutase gene expression and thiobarbituric acid-reactive substance content, was noted in diabetic rats, and both parameters were normalized by nitecapone treatment. In diabetic rats, activation of glomerular protein kinase C (PKC) was confirmed by isoform-specific translocation and Ser23 phosphorylation of the PKC substrate Na,KATPase. PKC-dependent changes in Na,K-ATPase phosphorylation were associated with decreased glomerular Na,K-ATPase activity. Nitecapone-treated diabetic rats were protected from these intracellular modifications. The combined results suggest that the COMTinhibitory and antioxidant properties of nitecapone provide a protective therapy against the development of diabetic nephropathy. Diabetes 49:1381-1389, 2000

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Section: Discussionmentioning

confidence: 97%

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confidence: 99%

Combined antioxidant and COMT inhibitor treatment reverses renal abnormalities in diabetic rats.

et al. 2000

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“…[51][52][53][54] HNE may change cellular functions in different steps, which may collectively work for an ultimate goal of disease progression. HNE is highly reactive with proteins and glutathiones, and it easily forms HNE-protein adducts and consumes the cellular glutathione pool.…”

Section: Discussionmentioning

confidence: 99%

Protein phosphatase 2A-linked and -unlinked caspase-dependent pathways for downregulation of Akt kinase triggered by 4-hydroxynonenal

et al. 2003

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We studied the signal pathways for regulation of serine/ threonine protein kinase Akt in Jurkat cells that had been treated with 4-hydroxynonenal (HNE) for caspase-dependent apoptosis induction. Treatment of cells with HNE led to a decrease in the level of Akt activity due to the dephosphorylation at Ser473, a major regulatory phosphorylation site. HNE-mediated dephosphorylation of Akt was prevented by a protein phosphatase 2A (PP2A) inhibitor, okadaic acid, and by a caspase-3 inhibitor, DEVD-CHO. HNE treatment resulted in an increase in the total level of PP2A activity, release of active tyrosine-dephosphorylated PP2A from the cytoskeleton and PP2A-Akt association, which were all dependent on caspase-3 activation. These results suggest that the level of PP2A activity is at least in part determined by its tyrosine phosphorylation, which is dually controlled by okadaic acid-sensitive phosphatases and protein-tyrosine kinases. Possibly underlying the mechanism of caspase-mediated activation of PP2A, HNE treatment resulted in downregulation of the activity of Src kinase, as a representative caspase-sensitive kinase to phosphorylate PP2A at tyrosine. In addition, activated caspase-3 partially cleaved Akt at a late stage of the apoptosis. These results indicate the existence of two distinct caspasedependent signal pathways for downregulation of Akt that works as a mechanism of positive feedback regulation for HNEtriggered apoptotic signals.

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“…It has been reported that oxidative stress is increased in diabetic conditions (Traverso et al, 1998) and is a major factor contributing to the extent of chronic diabetes complications (Baynes and Thorpe, 1999). A higher incidence of hepatic cancer has been reported to be associated with diabetes (Adami et al, 1996).…”

Section: Pretreatment With N-[2-(4-bromocinnamylamino)ethyl]-5-iso-mentioning

confidence: 99%

Insulin and Glucagon Regulation of GlutathioneS-Transferase Expression in Primary Cultured Rat Hepatocytes

Kim

Woodcroft

Novak

2003

J Pharmacol Exp Ther

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Diabetes is a major cause of morbidity and mortality, and complications resulting from diabetes have been attributed in part to increased oxidative stress. Glutathione S-transferases (GSTs) constitute a major protective mechanism against oxidative stress. Studies of the expression and activity of GSTs during diabetes are inconclusive, with both increased and decreased GST expression being reported in vivo. Insulin and glucagon effects on GST expression and the signaling pathway involved in the glucagon regulation of GST expression were examined in primary cultured rat hepatocytes. The addition of insulin resulted in the elevation of alpha-class GST protein levels, whereas alpha-and pi-class GST protein levels were markedly decreased in hepatocytes cultured with glucagon. In contrast, mu-class GST protein expression was unaffected by insulin or glucagon treatment. Insulin concentrations Ն1 nM resulted in increased GST activities and alpha-class GST protein levels, whereas glucagon concentrations Ն20 nM decreased alpha-and pi-class protein levels and activity. Treatment of cells with 8-bromo-cAMP or dibutyryl-cAMP also resulted in decreased alpha-and pi-class GST protein levels. Pretreatment with N-[2-(4-bromocinnamylamino)ethyl]-5-iso-quinoline sulfonamide (H89), a selective inhibitor of protein kinase A, before glucagon addition markedly attenuated the glucagon effect. This study demonstrates that insulin and glucagon regulate, in an opposing manner, the expression of alpha-class GSTs and that glucagon completely inhibits piclass GST expression in vitro, suggesting that hepatic GST expression may be decreased during diabetes. Furthermore, the present study implicates cAMP and protein kinase A in mediating the inhibitory effect of glucagon on GST expression.Diabetes mellitus is associated with a high risk of atherosclerosis and kidney, nerve, and tissue damage. It has been reported that oxidative stress is increased in diabetic conditions (Traverso et al., 1998) and is a major factor contributing to the extent of chronic diabetes complications (Baynes and Thorpe, 1999). A higher incidence of hepatic cancer has been reported to be associated with diabetes (Adami et al., 1996).The glutathione S-transferases (GSTs), abundantly expressed in liver tissue, constitute one of the major components of the phase II drug-metabolizing enzyme and antioxidant systems. The GSTs catalyze the conjugation of glutathione to a wide range of electrophiles and represent a protective mechanism against oxidative stress (Ketterer, 1998). Several members of the GST family exhibit seleniumindependent glutathione peroxidase activity, which plays an important role in protecting cells against lipid and nucleotide hydroperoxides (Sun et al., 1996;Ketterer, 1998).The GSTs comprise a complex and widespread enzyme superfamily that has been subdivided further into an everincreasing number of classes. The cytosolic GSTs are homo or heterodimeric enzymes, and the major GST subunits expressed in the adult liver are alpha-class subunits A1, A2,...

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Immunological evidence for increased oxidative stress in diabetic rats

Cited by 67 publications

References 35 publications

Combined antioxidant and COMT inhibitor treatment reverses renal abnormalities in diabetic rats.

Combined antioxidant and COMT inhibitor treatment reverses renal abnormalities in diabetic rats.

Protein phosphatase 2A-linked and -unlinked caspase-dependent pathways for downregulation of Akt kinase triggered by 4-hydroxynonenal

Insulin and Glucagon Regulation of GlutathioneS-Transferase Expression in Primary Cultured Rat Hepatocytes

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