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p38 MAPK Regulates Induction of HSPs in Human Esophageal Microvascular Endothelial Cells (HEMEC) in Response to Acidic pH Stress: Role of PI3/Akt
Author(s) -
rafiee parvaneh,
Theriot Monica,
Nelson Victoria,
Horowitz Scott,
Rogaczewski Aaron,
Johnson Christopher,
Shaker Reza
Publication year - 2006
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.20.4.a226-b
Subject(s) - p38 mitogen activated protein kinases , protein kinase b , heat shock protein , hsp27 , hsp70 , pi3k/akt/mtor pathway , mapk/erk pathway , cancer research , chemistry , inflammation , microbiology and biotechnology , heat shock , phosphorylation , immunology , biology , signal transduction , biochemistry , gene
The heat shock response maintains cellular homeostasis following noxious injury. Heat shock proteins (HSPs) are induced by stress and function to chaperone the denatured proteins. Gastroesophageal reflux disease (GERD) is linked to prolonged esophageal acid exposure and enhanced leukocyte recruitment, implying a role for local microvascular endothelium in esophageal inflammation. We investigated whether PI3K/Akt and MAPKs regulate HSPs induction in HEMEC following acidic pH exposure. Methods: Specific inhibitors of signaling pathways were used to define the role ofPI3K/Akt and MAPKs following acid exposure. Results: Acidic pH enhanced phosphorylation of MAPKs in HEMEC as well as inducing HSP27 and HSP70. SB203580, blocked both HSP27 and HSP70 mRNA induction, suggesting a role for p38 MAPK in HEMEC. Acidic exposure also increased inflammatory induction of VCAM‐1 protein via MAPK activation, but not ICAM‐1, which may play a key role in selective leukocyte (i.e. eosinophil) recruitment in esophagitis. Acidic pH activation correlated with altered cellular function in HEMEC involving cell survival mechanisms prevention of apoptosis via expression of HSP70 and activation of PI3k/Akt. Conclusion: These data suggest that HEMECs exposed to acidic refluxate, may undergo activation characterized by a disturbed mucosal squamous epithelial barrier, such as erosive reflux esophagitis and peptic esophageal ulceration. Supported by Digestive Disease Center and Cancer Center (P.R, D.G.B.)