Cephaloridine Induces Translocation of Protein Kinase C δ Into Mitochondria and Enhances Mitochondrial Generation of Free Radicals in the Kidney Cortex of Rats Causing Renal Dysfunction
スポンサーリンク
概要
- 論文の詳細を見る
We have previously reported that the enhancement of free radical generation in mitochondria isolated from the kidney cortex of rats exposed to cephaloridine (CER) is probably mediated by the activation of protein kinase C (PKC). We examined which isoenzymes of PKC might be involved in the development of nephrotoxicity induced by CER in rats. The CER-induced renal dysfunction observed 24 h after its injection was prevented by a potent antioxidant DPPD and well-known PKC inhibitors like H-7 and rottlerin. At 1.5 and 3.5 h after the CER injection, the free radical generation was increased markedly and this was associated with translocation of PKCδ into the mitochondria of renal cortex tissue. Pretreatment of rats with H-7, a PKC inhibitor, significantly inhibited the CER-derived increase in mitochondrial generation of free radicals, suggesting that H-7 probably gets into the mitochondria and inhibits the activity of translocated PKC within the mitochondria. It was also shown that pretreatment of rats with rottlerin, a specific inhibitor of PKCδ, suppressed the early translocation of PKCδ into mitochondria and inhibited the CER-derived development of renal dysfunction. These results suggest that the CER-derived early translocation of PKCδ into mitochondria probably leads to the enhanced production of free radicals through the mitochondrial respiratory chain during the development of the nephrotoxicity caused by CER. Understanding the role of PKCδ in mitochondria may provide an important clue to the molecular mechanisms of mitochondrial production of reactive oxygen species and the free radical-induced renal failure in rats treated with CER.
- 社団法人 日本薬理学会の論文
- 2005-05-20
著者
-
GEMBA Munekazu
Division of Pharmacology, Osaka University of Pharmaceutical Sciences
-
Kohda Yuka
Division Of Pharmacology Osaka University Of Pharmaceutical Sciences
-
Gemba Munekazu
Division Of Pharmacology Osaka University Of Pharmaceutical Sciences
-
Gemba Munekazu
Division Of Pharmacology Osaka University Of Farmaceutical Sciences
関連論文
- Protective Effect of Serum Thymic Factor, FTS, on Cephaloridine-Induced Nephrotoxicity in Rats(Pharmacology)
- Serum thymic factor (FTS) prevents cephaloridine-induced nephrotoxicity in rats (KIDNEYS AND URINARY EXCRETION SYSTEM) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th Annual Meeting)
- Structure-Activity Relationships of Dermorphin Analogues Containing Chiral Piperazin-2-one and Piperazine Derivatives
- Establishment of Highly Specific and Quantitative Immunoassay Systems for Staphylococcal Enterotoxin A, B, and C Using Newly-Developed Monoclonal Antibodies
- INVOLVEMENT OF ACTIVATION OF NADPH OXIDASE AND EXTRACELLULAR SIGNAL-REGULATED KINASE (ERK) IN RENAL CELL INJURY INDUCED BY ZINC
- Stimulation of p-Aminohippurate Transport in Renal Cortical Slices Prepared from Rats Treated with Ginsenosides
- Modulation by Cyclic AMP and Phorbol Myristate Acetate of Cephaloridine-Induced Injury in Rat Renal Cortical Slices
- Increases in Urinary Enzyme Excretion in Rats Depleted of Glutathione Inhibited by Scavenger of Oxygen Free Radicals
- Effects of Efonidipine Hydrochloride on Renal Arteriolar Diameters in Spontaneously Hypertensive Rats
- Synthesis and Opiate Activity of Pseudo-Tetrapeptides Containing Chiral Piperazin-2-one and Piperazine Derivatives
- Relationship of Intracellular Calcium and Oxygen Radicals to Cisplatin-Related Renal Cell Injury
- Hypoxia and Reoxygenation - Induced Injury of Renal Epithelial Cells: Effect of Free Radical Scavengers
- INVOLVEMENT OF RAF-1/MEK/ERK1/2 SIGNALING PATHWAY IN ZINC-INDUCED INJURY IN RAT RENAL CORTICAL SLICES
- PROTECTIVE EFFECT OF A PROTEIN KINASE INHIBITOR ON CELLULAR INJURY INDUCED BY CEPHALORIDINE IN THE PORCINE KIDNEY CELL LINE LLC-PK_1
- Relationship between Cisplatin or Nedaplatin-Induced Nephrotoxicity and Renal Accumulation(Pharmacology)
- 2C-10 Enhancement by Protein Kinase C Activation and Amelioration by Cyclic AMP of Cephaloridine-Inducd Injury in Rat Kidney Cortical Slices.
- Cephaloridine Induces Translocation of Protein Kinase C δ Into Mitochondria and Enhances Mitochondrial Generation of Free Radicals in the Kidney Cortex of Rats Causing Renal Dysfunction
- ANTIOXIDATIVE PROPERTIES OF HX-1920 IN PREVENTING DRUG-INDUCED NEPHROTOXICITY
- "C-13 Hepatocyte growth factor reduces cisplatin-induced injury in renal epithelial LLC-PK_1 cells.
- AMELIORATION BY INHIBITOR OF PROTEIN KINASE C AND PHOSPHODIESTERASE OF LLC-PK1 CELL INJURY INDUCED BY CEPHALORIDINE
- 21D-02-3 Amelioration by Tyrosine Kinase Activation of Free Radical-Induced Injury in Renal Cells.
- O10-05 Participation of PKC in Free Radical-Induced injury in Kidney of Rats Treated with Cephaloridine.
- SIGNALLING PATHWAY INVOLVEMENT IN RENAL INJURY
- Amelioration by CAMP of Cephaloridine-Induced Injury in the Porcine Kidney Cell Line LLC-PK_1
- Ameliorative Effect of Adenosine on Hypoxia-Reoxygenation Injury in LLC-PK_1, a Porcine Kidney Cell Line
- Participation of ERK activation in cephaloridineinduced injury in rat renal cortical slices.(GENERAL SESSION BY ORAL PRESENTATION)(KIDNEYS AND URINARY EXCRETION SYSTEM)
- Effect of N-N'-diphenyl-p-phenylenediamine pretreatment on urinary enzyme excretion in cisplatin nephrotoxicity in rats.
- Cisplatin-induced injury to calcium uptake by mitochondria in glutathione-depleted slices of rat kidney cortex.
- The Iron Chelator Deferoxamine Prevents Cisplatin-Induced Lipid Peroxidation in Rat Kidney Cortical Slices.
- Stimulatory effect of cisplatin on production of lipid peroxidation in renal tissues.
- Effect of cisplatin on in vitro production of lipid peroxides in rat kidney cortex.
- In Vitro Oxygenation Injury to Slices Prepared from Ischemic Kidney in Rats.
- Use of cultured renal epithelial cells for the study of cisplatin toxicity.
- W2-4 CULTURED RENAL EPITHELIAL CELLS