Regulation of protein kinase C isozymes in kidney regeneration.
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.
Dong
L
L
W. Alton Jones Cell Science Center, Inc., Lake Placid, New York 12046-1099.
Stevens
J L
JL
Fabbro
D
D
Jaken
S
S
D000818:Animals; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D003545:Cysteine / Q000031:analogs & derivatives* / Q000633:toxicity; D005492:Folic Acid / Q000633:toxicity*; D006984:Hypertrophy; D015151:Immunoblotting; D007527:Isoenzymes / Q000302:isolation & purification / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D009336:Necrosis; D009392:Nephrectomy; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011493:Protein Kinase C / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000378:metabolism; D012016:Reference Values; D012038:Regeneration; D013347:Subcellular Fractions / Q000201:enzymology
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D007527:Isoenzymes; D011955:Receptors, Drug; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D015240:Phorbol 12,13-Dibutyrate; C039961:S-(1,2-dichlorovinyl)cysteine; D005492:Folic Acid; D011493:Protein Kinase C; D003545:Cysteine