EXPRESSION OF P21(WAF1 CIP1/SDI1) AND P53 IN APOPTOTIC CELLS IN THE ADRENAL-CORTEX AND INDUCTION BY ISCHEMIA-REPERFUSION INJURY/

p21(WAF1/CIP1/SDI1), an inhibitor of cyclin-dependent kinases, is expr essed at varying levels in human adrenal glands removed during surgery or organ recovery, In glands with p21 mRNA, nuclear p21 immunoreactiv ity, which was occasionally extensive, colocalized with p53 immunoreac tivity and DNA damage, as evidenced by in situ end-labeling, Many cell s showed morphological features of apoptosis when observed by fluoresc ent DNA dye staining and electron microscopy. This pattern was also as sociated with high levels of cytoplasmic heat shock protein 70. To add ress the question of the origin of p21 expression in some human adrena l glands, rat adrenal glands were subjected to 30 min of ischemia foll owed by 8 h of reperfusion, Cells with nuclear p21 and p53 appeared in the adrenal cortex together with DNA damage detected by in situ end-l abeling, Nuclear p21 immunoreactivity was also produced in adrenal tis sue fragments incubated at 37 degrees C in vitro, However, in this cas e, p21 expression was confined to the cut edge of the tissue. In contr ast, p21 in human adrenal glands, as in ischemic rat glands, was withi n the inner regions of the cortex, supporting an origin of the protein in vivo rather than postmortem. The p53/p21 pathway of reaction to ce llular injury, potentially leading to apoptosis, may play a role in ti ssue damage such as that resulting from ischemia/reperfusion. In the h uman adrenal cortex this process may be a precursor of adrenal failure .