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W. Alton Jones Cell Science Center, Inc., Lake Placid, New York 12946-1099 [L. D., J. L. S., S. J.], and Department of Virology and Oncology, Pharmaceutical Division, CIBA-GEIGY, CH-4002 Basel, Switzerland [D. F.]
2 To whom requests for reprints should be addressed, at W. Alton Jones Cell Science Center, 10 Old Barn Road, Lake Placid, NY 12946.
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-(l,2-dichlorovinyl)-L-cysteine; and (c) compensatory renal hypertrophy. Immunoblot analyses demonstrated that 5 PKC isozymes,
, β,
,
and
, 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
-PKC.
-PKC, which is not a phorbol ester receptor, was also decreased.
- and
-PKCs were not changed. However,
-PKC was not down-modulated during compensatory hypertrophy induced by unilateral nephrectomy. Thus, the observed decrease of
-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
-PKC, occurs during chemical-induced renal regeneration and suggests a general role for PKC activation in non-phorbol ester tumor promotion.
1 This work was supported by USPHS Grant ES05670 to and CA37589 J. L. S. and S. J. This work was presented as partial fulfillment for the Ph.D. degree awarded to L. D. from Clarkson University (Potsdam, NY).
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 4/26/93. Accepted 7/27/93.
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