Translocation of protein kinase C ? and ? in rat glomerular mesangial cells cultured under high glucose conditions

Kikkawa, Ryuichi; Haneda, Masakazu; Uzu, T.; Koya, Daisuke; Sugimoto, Toshiro; Shigeta, Y.

doi:10.1007/s001250050186

Cited by 34 publications

(50 citation statements)

References 9 publications

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“…2 The level of PKC α in the membrane fraction of cells cultured under high glucose conditions was significantly higher than levels in control cells. 13 Furthermore, in diabetic rat glomeruli, immunoblot analysis of the PKC α isoform yielded the same results as those shower in cells cultured under hyperglycemic conditions. 29 Koya et al 3 reported that hyperglycemia activated PKC α and PKC I isoforms in the glomeruli of diabetic rats, and that the activity was inhibited by the administration of a PKC inhibitor.…”

Section: Discussionsupporting

confidence: 64%

“…[17][18][19][20][21][22][23][24][25] At least 11 isoforms of PKC have been identified in mammalian tissues, and these have been divided into three groups: classical PKC (cPKC), new PKC (nPKC), and atypical PKC (aPKC). 13,[26][27][28] The cPKC group comprises α, I, II, and γ isoforms. These isoforms are Ca 2ϩ -dependent for their enzymatic activity.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12] Activation of the DAG-PKC-ERK pathway induces enhanced extracellular matrix protein and transforming growth factor (TGF)-expression, suggesting that PKCinduced activation of the MAPK cascade may be responsible for PKC-related abnormalities in diabetic glomeruli, leading to the development of DN. 5,9,13 However, whether the expression of PKC mRNA is enhanced in tissues of human DN is unknown. In the present study, we determined the localization and expression of PKC α and PKC I mRNA, by in-situ hybridization, in renal tissue samples from kidneys affected by DN and normal human kidney (NHK).…”

Section: Introductionmentioning

confidence: 98%

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In-situ hybridization studies of protein kinase C α and β I isoforms in human diabetic nephropathy

Toyoda

Suzuki

Zhang

et al. 2001

Clinical and Experimental Nephrology

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Background. Hyperglycemia is the most important contributor to the development of diabetic nephropathy (DN). The activation of protein kinase C (PKC) caused by hyperglycemia is implicated in the pathogenesis of DN. PKC, which comprises a family of enzymes, plays a role in many signal transduction pathways and is involved in the regulation of cell growth and differentiation. However, the precise role of PKC in the progression of human DN is not fully understood. Methods. To evaluate the pathological role of PKC in DN, we examined the mRNA expression levels of PKC α and PKC I isoforms in normal renal tissues and in renal tissues affected by DN. Tissues from open renal biopsies were obtained from 20 type 2 diabetic patients with DN. The expression levels of PKC α and PKC I mRNA in kidneys with DN and in normal human kidney (NHK) were evaluated by in-situ hybridization, using digoxigenin-labeled oligonucleotide probes. Results. Cells positive for PKC α and I mRNA were mainly observed in glomeruli, and some mRNA was also detected in the tubulointerstitium. The percentages of glomerular cells positive for PKC α and I mRNA were higher in kidneys with DN than in NHK. In the glomeruli of kidneys with DN, the percentage of cells positive for PKC I mRNA, but not the percentage of cells positive for PKC α mRNA, tended to be decreased with the degree of mesangial expansion. Conclusions. Our results suggest that the expression of mRNA for PKC α and/or I may be associated with the progression of DN.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

In-situ hybridization studies of protein kinase C α and β I isoforms in human diabetic nephropathy

Toyoda

Suzuki

Zhang

et al. 2001

Clinical and Experimental Nephrology

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“…However, it should be noted that other PKC isoforms have been found to be stimulated by high glucose as well, including PKC-ζ, PKC-δ, PKC-ε, etc. [45, 46, 47]. Further studies with specific inhibitors or the use of genetic manipulation to selectively block discrete isoforms is required to ascertain the relative importance of the PKC isoforms in this context.…”

Section: Mechanisms Underlying High Glucose-induced Stimulation Of Tgf-βmentioning

confidence: 99%

Novel Aspects of Transforming Growth Factor-Beta in Diabetic Kidney Disease

Tsuchida

Cronin²,

Sharma³

2002

Nephron

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“…Recent studies have reported that polyol pathway exists in mesangial cells and may play a role in the development of mesangial cell dysfunction caused by hyperglycemia [4, 5]. The activation of protein kinase C may play a critical role in the development of diabetic nephropathy characterized by mesangial cell proliferation and matrix expansion [6, 7]. Protein kinase C is activated by hyperglycemia-induced increases in diacylglycerol level, partly due to de novo synthesis [8, 9].…”

Section: Introductionmentioning

confidence: 99%

Troglitazone Inhibits Isolated Cell Proliferation, and Induces Apoptosis in Isolated Rat Mesangial Cells

Tsuchiya¹,

Shimizu²,

Shimomura³

et al. 2003

Am J Nephrol

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Background/Aims: Troglitazone is one of thiazolidinedione derivatives as a high affinity ligand for peroxisome proliferator-activated receptor-gamma (PPAR-γ). The in vivo studies demonstrated that troglitazone ameliorated microalbuminuria. There have been few reports about direct effect of thiazolidinedione derivatives on mesangial cell function. We determined the effect of troglitazone on isolated rat mesangial cell proliferation. Methods: We determined PPAR-γ mRNA expression in isolated rat mesangial cells. Chronic effects of 10^–6 to 10^–4 mol/l troglitazone on mesangial cell proliferation and mitogen-activated protein (MAP) kinase activity were also determined. The effects of troglitazone on apoptosis were investigated in rat mesangial cells. Results: Rat PPAR-γ mRNA was detected in isolated rat mesangial cells. Living cell number, assessed by colorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) assay, was significantly decreased with 10^–4 mol/l troglitazone. The addition of 10^–6 to 10^–4 mol/l troglitazone dose-dependently inhibited 5-bromo-2′-deoxyuridine (BrdU) uptake into isolated rat mesangial cells. The addition of 10^–4 and 10^–5 mol/l troglitazone significantly reduced MAP kinase activity. Troglitazone at the concentrations of 10^–6 to 10^–4 mol/l dose-dependently increased DNA fragmentation rates, indicating that troglitazone may cause apoptosis in rat mesangial cells. Bax and Bcl-xL proteins were not changed, although Bcl-2 proteins increased with troglitazone. Conclusions: The present data demonstrated that troglitazone inhibits cell proliferation, and induces apoptosis in rat mesangial cells, raising a possibility that it directly affects renal function.

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Translocation of protein kinase C ? and ? in rat glomerular mesangial cells cultured under high glucose conditions

Cited by 34 publications

References 9 publications

In-situ hybridization studies of protein kinase C α and β I isoforms in human diabetic nephropathy

In-situ hybridization studies of protein kinase C α and β I isoforms in human diabetic nephropathy

Novel Aspects of Transforming Growth Factor-Beta in Diabetic Kidney Disease

Troglitazone Inhibits Isolated Cell Proliferation, and Induces Apoptosis in Isolated Rat Mesangial Cells

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