Reactive oxygen species blockade and action of insulin on expression of angiotensinogen gene in proximal tubular cells

2004/12/01 by Tusty-Jiuan Hsieh, Tusty‐Jiuan Hsieh, Pierre Fustier +14 · 14 citations
Chemistry · Medicine · #Action (physics) #Biology #Blockade #Cell biology #Chemistry #Endocrinology #Gene #Gene expression #Genetics #Hormonal Regulation and Hypertension #Insulin #Internal medicine #Medicine #Nitric Oxide and Endothelin Effects #Reactive oxygen species #Receptor #Renin-Angiotensin System Studies

paper · pdf · doi:10.1677/joe.1.05871

openalex publication_date 2004/12/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

We reported previously that insulin inhibits the stimulatory effect of high glucose on the expression of angiotensinogen (ANG) gene in both rat immortalized renal proximal tubular cells (IRPTCs) and non-diabetic rat renal proximal tubular cells (RPTCs), but has no effect in diabetic rat RPTCs. In the present study we investigated whether hyperglycaemia-induced resistance to the insulin-induced inhibition of expression of the ANG gene is mediated via the generation of reactive oxygen species (ROS) in RPTCs. Rat IRPTCs were cultured for 2 weeks in high-glucose (25 mM) or normal-glucose (5 mM) medium plus angiotensin II (Ang II) with or without a superoxide scavenger (tiron), or inhibitors of: NADPH oxidase (diphenylene iodinium, DPI), Ang II type 1 and 2 receptors (losartan and PD123319), angiotensin-converting enzyme (perindopril), protein kinase C (GF 109203X), or glutamine:fructose-6-phosphate amino-transferase (azaserine). Cellular generation of ROS, and ANG and renin mRNA levels were assessed by lucigenin assay and specific reverse transcriptase-PCR respectively. Phosphorylation of p44/42 mitogen-activated protein kinase (p44/42 MAPK) was evaluated by western blotting. Prolonged exposure of IRPTCs to high concentrations of glucose or Ang II evoked generation of ROS and resistance to the insulin-induced inhibition of expression of the ANG gene and of p44/42 MAPK phosphorylation. Co-incubation of IRPTCs with tiron, DPI, losartan, PD123319, perindopril, GF 109203X or azaserine prevented ROS generation, restoring the inhibitory action of insulin on ANG gene expression and on p44/42 MAPK phosphorylation. In conclusion, our studies demonstrate that blockade of both ROS generation and activation of the intrarenal renin-angiotensin system improves the inhibitory action of insulin on ANG gene expression in IRPTCs in conditions of high glucose.

Cited by

• Maternal diabetes modulates renal morphogenesis in offspring. [europepmc]
• Sequential activation of the reactive oxygen species/angiotensinogen/renin-angiotensin system axis in renal injury of type 2 diabetic rats. [europepmc]
• Redox control of renal function and hypertension. [europepmc]
• Role of activated intrarenal reactive oxygen species and renin-angiotensin system in IgA nephropathy model mice. [europepmc]
• Mechanisms of intermittent hypoxia induced hypertension. [europepmc]
• Reactive oxygen species promote caspase-12 expression and tubular apoptosis in diabetic nephropathy. [europepmc]
• Cilnidipine suppresses podocyte injury and proteinuria in metabolic syndrome rats: possible involvement of N-type calcium channel in podocyte. [europepmc]
• High glucose augments angiotensinogen in human renal proximal tubular cells through hepatocyte nuclear factor-5. [europepmc]
• Advanced Glycation End Products Stimulate Angiotensinogen Production in Renal Proximal Tubular Cells. [europepmc]
• Canagliflozin Prevents Intrarenal Angiotensinogen Augmentation and Mitigates Kidney Injury and Hypertension in Mouse Model of Type 2 Diabetes Mellitus. [europepmc]
• Blockade of sodium-glucose cotransporter 2 suppresses high glucose-induced angiotensinogen augmentation in renal proximal tubular cells. [europepmc]
• Urinary angiotensinogen increases in the absence of overt renal injury in high fat diet-induced type 2 diabetic mice. [europepmc]
• Angiotensin II biphasically regulates cell differentiation in human iPSC-derived kidney organoids. [europepmc]
• Immunosuppression by Mycophenolate Mofetil Mitigates Intrarenal Angiotensinogen Augmentation in Angiotensin II-Dependent Hypertension. [europepmc]

Related

• Intrarenal renin–angiotensin system inactivation ameliorates tubulopathy via attenuation of mitochondrial oxidative stress, dysfunction and senescence in diabetes
• Angiotensin II Contributes to Diabetic Renal Dysfunction in Rodents and Humans via Notch1/Snail Pathway
• New insights into the pathophysiology of diabetic nephropathy: from haemodynamics to molecular pathology
• Oxidative Stress and Diabetic Complications
• Protective Effects of GLP-1 on Glomerular Endothelium and Its Inhibition by PKCβ Activation in Diabetes