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Anti‐apoptotic mechanism(s) of angiotensin 1‐7/mas in alveolar epithelial cell survival (1010.3)
Author(s) -
Gopallawa Indiwari,
Uhal Bruce
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1010.3
Subject(s) - apoptosis , autocrine signalling , angiotensin ii , kinase , cancer research , protein kinase a , endocrinology , chemistry , medicine , receptor , biology , microbiology and biotechnology , biochemistry
Earlier work showed that autocrine synthesis of angiotensin II (ANGII) and c‐Jun‐N‐terminal kinase phosphorylation (pJNK) are required events in alveolar epithelial cell (AEC) apoptosis which is linked to severe lung diseases. Angiotensin 1‐7 (ANG 1‐7) prevents AEC apoptosis which is induced by locally synthesized ANG II. However the exact inhibitory mechanisms of ANG 1‐7/mas are currently unclear in AECs. The objective of the current research is to identify molecular mechanism(s) by which ANG1‐7 promotes AEC survival. We hypothesized that ANG 1‐7 activates a map kinase phosphatase (MKP) and maintains low pJNK levels thereby preventing apoptosis. To evaluate whether adding ANG 1‐7 acts through MKP‐2, freshly prepared ANG 1‐7 (0.1µM) in serum free media was added to a mouse lung epithelial cell line (MLE‐12). Cell lysates were run on 10% SDS‐PAGE to detect MKP‐2 protein by Western blotting. Current preliminary data suggests that ANG 1‐7 increased MKP‐2 protein (p=0.0286). Further, blockade of endogenous ANG 1‐7 with the mas receptor antagonist A779 reduced MKP‐2 levels (p=0.0014). Moreover data shows that inhibition of protein kinase A (PKA) in MLE‐12s induced pJNK and hence may be involved in promoting AEC survival. The results from these studies suggest that MKP‐2 is a key protein in the ANG 1‐7/mas pathway, and may provide insights to potential therapeutic strategies for lung diseases that involve AEC apoptosis. Grant Funding Source : Supported by HL‐45136