Glucose-induced protein kinase C activity regulates arachidonic acid release and eicosanoid production by cultured glomerular mesangial cells
| Autor: | R W Schrier, B Williams |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
medicine.medical_specialty
Glomerular Mesangial Cell Molecular Sequence Data education Tritium Phospholipases A Piperazines Substrate Specificity Rats Sprague-Dawley chemistry.chemical_compound Alkaloids 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine Internal medicine medicine Animals Mannitol Amino Acid Sequence Cells Cultured Protein Kinase C Protein kinase C Arachidonic Acid Mesangial cell General Medicine Isoquinolines Staurosporine Angiotensin II Culture Media Glomerular Mesangium Rats Thromboxane B2 Kinetics Glucose Endocrinology chemistry Eicosanoid Prostaglandins Eicosanoids lipids (amino acids peptides and proteins) Arachidonic acid Oligopeptides Research Article Eicosanoid Production |
| Zdroj: | Journal of Clinical Investigation. 92:2889-2896 |
| ISSN: | 0021-9738 |
| Popis: | Changes in glomerular eicosanoid production have been implicated in the development of diabetes-induced glomerular hyperfiltration and glomerular mesangial cells (GMC) are major eicosanoid-producing cells within the glomerulus. However, the mechanism for the effect of diabetes mellitus on glomerular mesangial eicosanoid production is unknown. The present study therefore examined whether elevated glucose concentrations activate protein kinase C (PKC) in GMC and whether this PKC activation mediates an effect of elevated glucose concentrations to increase the release of arachidonic acid and eicosanoid production by GMC. The percentage of [3H]arachidonic acid release per 30 min by preloaded GMC monolayers was significantly increased after 3-h exposure to high glucose (20 mM) medium (177% vs control medium) and this increase was sustained after 24-h exposure to high glucose concentrations. 3-h and 24-h exposure to high glucose medium also increased PGE2, 6-keto-PGF1 alpha, and thromboxane (TXB2) production by GMC. High glucose medium (20 mM) increased PKC activity in GMC at 3 and 24 h (168% vs control). In contrast, osmotic control media containing either L-glucose or mannitol did not increase arachidonic acid release, eicosanoid production, or PKC activity in GMC. Inhibiting glucose-induced PKC activation with either H-7 (50 microM) or staurosporine (1 microM) prevented glucose-induced increases in arachidonic acid release and eicosanoid production by GMC. These data demonstrate that elevated extracellular glucose concentrations directly increase the release of endogenous arachidonic acid and eicosanoids by GMC via mechanisms dependent on glucose-induced PKC activation. |
| Databáze: | OpenAIRE |
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