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Regulation of protein kinase C isozymes in kidney regeneration
L Dong1, J L Stevens, D Fabbro
1W. Alton Jones Cell Science Center, Inc., Lake Placid, New York 12046-1099.
Abstract:
Tissue damage and repair processes are important factors in renal tumor progression. To determine whether protein kinase C (PKC) is involved in these processes, we characterized PKC isozymes during rat kidney regeneration using 3 models: (a) diffuse cortical hyperplasia and hypertrophy induced by folic acid; (b) focal necrosis of the S3 segments induced by S-(1,2-dichlorovinyl)-L-cysteine; and (c) compensatory renal hypertrophy. Immunoblot analyses demonstrated that 5 PKC isozymes, alpha, beta, delta, epsilon, and zeta, were expressed in rat kidney. Six h after folic acid treatment, phorbol ester receptors were down-modulated. Down-modulation preceded an increase in DNA synthesis which was maximal at 24 h. The reduction in phorbol ester receptors was due largely to a decrease in alpha-PKC. zeta-PKC, which is not a phorbol ester receptor, was also decreased. delta- and epsilon-PKCs were not changed. However, alpha-PKC was not down-modulated during compensatory hypertrophy induced by unilateral nephrectomy. Thus, the observed decrease of alpha-PKC after folic acid treatment is most likely associated with the hyperplastic and not the hypertrophic effects of this renal toxin. These results demonstrate that activation-associated down-modulation of PKC, in particular alpha-PKC, occurs during chemical-induced renal regeneration and suggests a general role for PKC activation in non-phorbol ester tumor promotion.
Insights
Protein kinase C (PKC) plays a role in kidney regeneration. Alpha-PKC down-modulation during chemical-induced regeneration suggests its involvement in tumor promotion.
Area of Science:
- Renal cell biology
- Molecular mechanisms of tissue repair
- Biochemistry of signal transduction
Background:
- Tissue damage and repair are critical in renal tumor progression.
- Protein kinase C (PKC) isozymes are implicated in cellular processes.
- Understanding PKC's role in kidney regeneration is essential.
Purpose of the Study:
- To investigate the involvement of PKC isozymes in rat kidney regeneration.
- To characterize PKC isozyme expression and modulation during different regeneration models.
- To explore the potential role of PKC in renal tumor promotion.
Main Methods:
- Utilized three rat kidney regeneration models: folic acid-induced hyperplasia/hypertrophy, S-(1,2-dichlorovinyl)-L-cysteine-induced necrosis, and compensatory hypertrophy.
- Employed immunoblot analyses to detect and quantify PKC isozymes (alpha, beta, delta, epsilon, zeta).
- Assessed phorbol ester receptor modulation and DNA synthesis post-treatment.
Main Results:
- Five PKC isozymes (alpha, beta, delta, epsilon, zeta) were detected in rat kidneys.
- Folic acid treatment led to down-modulation of phorbol ester receptors, primarily alpha-PKC, preceding increased DNA synthesis.
- Alpha-PKC was not down-modulated during compensatory hypertrophy, suggesting its specific association with hyperplastic effects.
Conclusions:
- Activation-associated down-modulation of PKC, particularly alpha-PKC, occurs during chemical-induced renal regeneration.
- The findings suggest a role for PKC activation in non-phorbol ester tumor promotion in the kidney.
- PKC modulation differs between hyperplastic and hypertrophic renal regeneration processes.