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GLP‐1 Analogue, Exendin‐4, Modulates MAPKs Activity but not the Heat Shock Response in Human HepG2 Cells
Author(s) -
Madhu Dhanya,
Hammad Maha,
Kavalakatt Sina,
Khadir Abdelkrim,
Tiss Ali
Publication year - 2018
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.201600169
Subject(s) - mapk/erk pathway , p38 mitogen activated protein kinases , heat shock protein , phosphorylation , glucose homeostasis , kinase , microbiology and biotechnology , biology , medicine , endocrinology , chemistry , insulin resistance , biochemistry , insulin , gene
Purpose Glucagon‐like peptide‐1 (GLP‐1) analogues reduce ER stress and inflammation in key metabolic organs, including the liver. However, their effects on heat shock response (HSR) and mitogen‐activated protein kinases (MAPKs) have not yet been elucidated. In the present study, we investigate whether the GLP‐1 analogue, exendin‐4, triggers the expression of HSR and increases MAPK activity under metabolic stress. Experimental design The effects of exendin‐4 in the presence or absence of palmitic acid (PA; 400 μ m ) or glucose (30 m m ) in the HepG2 liver cell line are assessed using Western blots, quantitative real‐time PCR, and label‐free proteomics. Results Heat shock proteins (HSP60, HSP72, HSP90, and GRP78) and other chaperones are not significantly affected by exendin‐4 under the conditions tested. In contrast, the presence of exendin‐4 alone increases the MAPK phosphorylation levels (JNK, ERK1/2, and p38). For short incubation periods, in the presence of PA or glucose, treatment with exendin‐4 exhibits limited effects but significantly attenuates MAPK phosphorylation after a 24‐h incubation. Interestingly, canonical signaling pathways, such as EIF2, ILK, PKA, and Rho, are modulated by exendin‐4. Conclusion and clinical relevance Identifying new pathways modulated by GLP‐1 analogues will provide further insights into their benefits beyond their currently recognized roles in glycemic control, such as MAPK activity, energy homeostasis, and body weight decrease.