Increased expression of sulfated glycoprotein-2 and DNA fragmentation in the pancreas of copper-deficient rats.

Recent morphological studies from our laboratory have shown that copper deficiency-induced pancreatic involution in rats is secondary to apoptosis (M. S. Rao, A. V. Yeldandi, V. Subbarao, and J. K. Reddy, 1993, Am. J. Pathol. 142, 1952-1957). To corroborate the morphological findings, we have examined pancreases from copper-deficient rats for expression of sulfated glycoprotein-2 (SGP-2) mRNA and DNA fragmentation, which are considered as specific markers of apoptosis. Agarose gel electrophoresis of the DNA extracted from pancreases of rats maintained on copper deficient diet (CUDD) for 5 and 7 weeks showed characteristic "ladder" pattern, whereas DNA from control rats and rats maintained on CUDD for 3 weeks showed no fragmentation. These findings correlated well with the histological changes. Northern blot analysis of total RNA revealed a marked increase in the expression of SGP-2 mRNA at 5 weeks followed by a gradual decrease at 6 and 7 weeks. These results further support that the mechanism of copper deficiency-induced pancreatic involution is through apoptosis.