Decreased mitogen activated protein kinase activities in congenital diaphragmatic hernia-associated pulmonary hypoplasia

Background/Purpose: The mechanisms that cause pulmonary hypoplasia associat ed with congenital diaphragmatic hernia (CDH) currently are unknown. The au thors proposed that the reduced size and immaturity of these lungs may be a ssociated with differences in the levels of mitogen activated protein (MAP) kinase phosphorylation (extracellular signal regulated protein kinases, ER K-1 and -2). Methods: ERK-1 activities were measured using immune-complex kinase assays on fetal whole-lung lysates obtained from both nitrofen and olive oil-treat ed (control) pregnant rats. In addition, ERK-1 and ERK-2 functional activit ies were estimated by semiquantitative Western blot analysis, using an anti body specific for the diphosphorylated (dp-ERK, activated) forms of the enz ymes. Results: ERK-1 activities, measured using immune-complex kinase assays, wer e reduced in CDH lungs compared with olive oil-treated controls (P < .02). In addition, dp-ERK-1 and dp-ERK-2 levels were found to be reduced in CDH l ungs compared with controls (dp-ERK-1, P = .003; dp-ERK-2, P = .04), wherea s ERK-1 and ERK-2 protein levels were unchanged. Conclusions: The lower values of ERK-1 activity and reduced amounts of dp-E RK-1 and dp-ERK-2 in lung tissue from CDH animals, suggests that ERK-1 and ERK-2 activities are reduced in pulmonary hypoplasia associated with CDH. T he observed reduction in ERK-1 and ERK-2 activities implicates attenuated c ell signaling upstream of the ERK-1 and -2 enzymes. Copyright (C) 2001 by W .B. Saunders Company.