Advanced Glycation End Product-Induced Peroxisome Proliferator-Activated Receptor γ Gene Expression in the Cultured Mesangial Cells

Iwashima, Yasunori; Eto, Masashi; Horiuchi, Seikoh; Sano, Hiroaki

doi:10.1006/bbrc.1999.1539

Cited by 55 publications

(38 citation statements)

References 62 publications

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“…On the other hand, the sucrose-induced increase in PPARγ, the adipocyte-predominant transcription factor found in low abundance in the heart [47], may serve as an insulin sensitiser to regulate glucose and lipid homeostasis [17]. PPARγ may be upregulated in a compensatory manner by excessive accumulation of reactive oxygen species [48], as seen in our current study. It can be speculated that the antioxidant metallothionein reconciles the imbalanced redox status triggered by insulin resistance under the present experimental setting, thus restoring the normal insulin-signalling mechanisms at the levels of insulin receptor β, insulin receptor tyrosine phosphorylation, Akt phosphorylation, PTP1B and PPARγ.…”

Section: Discussionsupporting

confidence: 64%

Metallothionein alleviates cardiac contractile dysfunction induced by insulin resistance: role of Akt phosphorylation, PTB1B, PPARγ and c-Jun

et al. 2005

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Aims/hypothesis: Insulin resistance is concomitant with metabolic syndrome, oxidative stress and cardiac contractile dysfunction. However, the causal relationship between oxidative stress and cardiac dysfunction is unknown. This study was designed to determine the impact of overexpression of the cardiac antioxidant metallothionein on cardiac dysfunction induced by insulin resistance in mice. Methods: Whole-body insulin resistance was generated in wild-type FVB and metallothionein transgenic mice by feeding them with sucrose for 12 weeks. Contractile and intracellular Ca 2+ properties were evaluated in ventricular myocytes using an IonOptix system. The contractile indices analysed included: peak shortening (PS), time to 90% PS (TPS 90 ), time to 90% relengthening (TR 90 ), halfwidth duration, maximal velocity of shortening (+dL/dt) and relengthening (−dL/dt), fura-fluorescence intensity change (ΔFFI) and decay rate (τ). Results: The sucrose-fed mice displayed glucose intolerance, enhanced oxidative stress, hyperinsulinaemia, hypertriglyceridaemia and normal body weight. Compared with myocytes in starch-fed mice, those from sucrose-fed mice exhibited depressed PS, +dL/dt, −dL/ dt, prolonged TR 90 and decay rate, and reduced ΔFFI associated with normal TPS 90 and half-width duration. Western blot analysis revealed enhanced basal, but blunted insulin (15 mU/g)-stimulated Akt phosphorylation. It also showed elevated expression of insulin receptor β, insulin receptor tyrosine phosphorylation, peroxisome proliferatoractivated receptor γ, protein tyrosine phosphatase 1B and phosphorylation of the transcription factor c-Jun, associated with a reduced fold increase of insulin-stimulated insulin receptor tyrosine phosphorylation in sucrose-fed mice. All western blot findings may be attenuated or ablated by metallothionein. Conclusions/interpretation: These data indicate that oxidative stress may play an important role in cardiac contractile dysfunction associated with glucose intolerance and possibly related to alteration in insulin signalling at the receptor and post-receptor levels.

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Section: Discussionsupporting

confidence: 64%

Metallothionein alleviates cardiac contractile dysfunction induced by insulin resistance: role of Akt phosphorylation, PTB1B, PPARγ and c-Jun

et al. 2005

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“…AGE-induced modification of signal transduction pathways occur through the induction of PKC activation, but may also occur independent of PKC activation (32). In mesangial cells, the independent activation of NF-B and PKC pathways due to AGE presence in vitro is thought to be an early event contributing to oxidative stress (33).…”

Section: Discussionmentioning

confidence: 99%

Receptor for Advanced Glycation End Products (RAGEs) and Experimental Diabetic Neuropathy

et al. 2008

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OBJECTIVE-Heightened expression of the receptor for advanced glycation end products (RAGE) contributes to development of systemic diabetic complications, but its contribution to diabetic neuropathy is uncertain. We studied experimental diabetic neuropathy and its relationship with RAGE expression using streptozotocin-induced diabetic mice including a RAGE Ϫ/Ϫ cohort exposed to long-term diabetes compared with littermates without diabetes.RESEARCH DESIGN AND METHODS-Structural indexes of neuropathy were addressed with serial (1, 3, 5, and 9 months of experimental diabetes) electrophysiological and quantitative morphometric analysis of dorsal root ganglia (DRG), peripheral nerve, and epidermal innervation. RAGE protein and mRNA levels in DRG, peripheral nerve, and epidermal terminals were assessed in WT and RAGE Ϫ/Ϫ mice, with and without diabetes. The correlation of RAGE activation with nuclear factor (NF)-B and protein kinase C ␤II (PKC␤II) protein and mRNA expression was also determined. RESULTS-Diabetic peripheral epidermal axons, sural axons,Schwann cells, and sensory neurons within ganglia developed dramatic and cumulative rises in RAGE mRNA and protein along with progressive electrophysiological and structural abnormalities. RAGE Ϫ/Ϫ mice had attenuated structural features of neuropathy after 5 months of diabetes. RAGE-mediated signaling pathway activation for NF-B and PKC␤II pathways was most evident among Schwann cells in the DRG and peripheral nerve.CONCLUSIONS-In a long-term model of experimental diabetes resembling human diabetic peripheral neuropathy, RAGE expression in the peripheral nervous system rises cumulatively and relates to progressive pathological changes. Mice lacking RAGE have attenuated features of neuropathy and limited activation of potentially detrimental signaling pathways. Diabetes

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“…It has recently been demonstrated that this receptor is also expressed in a wide variety of cells, including monocytes and macrophages. Activation by various stimuli, including phorbol myristate acetate, lipopolysaccharide, advanced glycation end products, and phagocytosis of ox-LDL, could enhance PPAR␥ expression by monocytes and macrophages (10,21,22). Increased expression of PPAR␥ has also been documented at sites of inflammation in arthritis and colitis and in foam cells from atherosclerotic plaques (23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

Rapid induction of peroxisome proliferator–activated receptor γ expression in human monocytes by monosodium urate monohydrate crystals

Akahoshi¹,

Namai²,

Murakami³

et al. 2003

Arthritis & Rheumatism

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Objective. Peroxisome proliferator-activated receptor ␥ (PPAR␥) is a member of the nuclear hormone receptor superfamily and functions as a key regulator of lipid and glucose metabolism, atherosclerosis, and inflammatory responses. This study was undertaken to evaluate the biologic role of PPAR␥ in self-limiting episodes of acute gouty arthritis. To do this, we investigated PPAR␥ expression by monosodium urate monohydrate (MSU) crystal-stimulated monocytes, and we studied the effects of PPAR␥ ligands on crystal-induced acute inflammation.Methods. PPAR␥ expression by MSU crystalstimulated human peripheral blood mononuclear cells was determined by reverse transcription-polymerase chain reaction and immunostaining. Expression of CD36 on monocytes was detected by flow cytometric analysis. The effects of PPAR␥ ligands on in vitro crystal-induced cytokine production and on in vivo cellular infiltration during crystal-induced acute inflammation were also investigated.Results. MSU crystals rapidly and selectively induced PPAR␥ expression by monocytes. Gene expression was detected as early as 2 hours, and maximum expression was observed at 4 hours after stimulation. The induced PPAR␥ was functional, since a PPAR␥ ligand was able to up-regulate CD36 expression on monocytes. A natural ligand of PPAR␥, 15-deoxy-⌬ 12,14 -prostaglandin J 2 (15deoxy-PGJ 2 ), significantly reduced the crystal-induced production of cytokines by monocytes. Indomethacin inhibited cytokine production only at high concentrations, and an antidiabetic thiazolidinedione (troglitazone) failed to exert significant effects. Administration of troglitazone and 15deoxy-PGJ 2 significantly prevented cellular accumulation in a mouse air-pouch model of MSU crystal-induced acute inflammation.Conclusion. Rapid induction of PPAR␥ expression on monocytes by MSU crystals may contribute, at least in part, to the spontaneous resolution of acute attacks of gout.

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Advanced Glycation End Product-Induced Peroxisome Proliferator-Activated Receptor γ Gene Expression in the Cultured Mesangial Cells

Cited by 55 publications

References 62 publications

Metallothionein alleviates cardiac contractile dysfunction induced by insulin resistance: role of Akt phosphorylation, PTB1B, PPARγ and c-Jun

Metallothionein alleviates cardiac contractile dysfunction induced by insulin resistance: role of Akt phosphorylation, PTB1B, PPARγ and c-Jun

Receptor for Advanced Glycation End Products (RAGEs) and Experimental Diabetic Neuropathy

Rapid induction of peroxisome proliferator–activated receptor γ expression in human monocytes by monosodium urate monohydrate crystals

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