Premium
Inhibition of Apoptosis by Angiotensin 1‐7/mas Pathway through MKP‐2 Activation in Alveolar Epithelial Cells
Author(s) -
Gopallawa Indiwari,
Uhal Bruce
Publication year - 2015
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.29.1_supplement.569.14
Subject(s) - apoptosis , angiotensin ii , chemistry , autocrine signalling , blot , dna fragmentation , transfection , kinase , microbiology and biotechnology , cancer research , receptor , endocrinology , biology , programmed cell death , biochemistry , gene
Study Objective: The autocrine generation of angiotensin II (ANGII) and c‐Jun‐N‐ terminal kinase phosphorylation (pJNK) are both required in alveolar epithelial cell (AEC) apoptosis which contributes to lung diseases. Angiotensin 1‐7 (ANG 1‐7) protects against AEC apoptosis which is induced by ANG II. However the exact inhibitory mechanisms of ANG 1‐7 and the mas receptor are currently unclear in AECs. The objective of the current research is to identify the role of map kinase phosphatase (MKP‐2) in AEC survival. We hypothesized that ANG 1‐7 activates MKP‐2 and maintains low pJNK levels thereby preventing apoptosis. Methods To determine the functional role(s) of MKP‐2, AECs were transfected with MKP‐2 siRNAs in the presence of ANG II (0.1µM) and/or ANG I‐7 (0.1µM). Then the cells were subjected to determine pJNK and apoptosis by Western blotting and nuclear fragmentation assay respectively. The loss of mitochondrial membrane potential (MMP) was also measured using a lipophilic probe. To test the involvement of mas receptor the cells were transfected with anti‐sense oligonucleotides in the presence of ANG 1‐7 followed by Western blotting to detect MKP‐2 Results The current data show the induction of pJNK (p<0.01), nuclear fragmentation (p<0.01) and MMP (p<0.001) when MKP‐2 is knocked down. The data also show that silencing MKP‐2 prevented the blockade of apoptosis by ANG 1‐7. Moreover the blockade of the mas receptor by the antagonist (A779) or anti‐sense oligonucleotides attenuated the induction of MKP‐2 by ANG 1‐7 Conclusions The results from these studies suggest that ANG 1‐7/mas activation prevents JNK phosphorylation by activating the JNK selective phosphatase MKP‐2 and further it shows the involvement of mas receptor in MKP‐2 activation.