Nucleotide-binding oligomerization domain protein 2 attenuates ER stress-induced cell death in vascular smooth muscle cells
Autor: | Seon-Jin Lee, Min-Young Kwon, Narae Hwang, Su Wol Chung |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Cell death
Programmed cell death Vascular smooth muscle XBP1 Biochemistry NOD2 03 medical and health sciences chemistry.chemical_compound Vascular smooth muscle cells Molecular Biology 0303 health sciences Chemistry Endoplasmic reticulum Tunicamycin 030302 biochemistry & molecular biology General Medicine musculoskeletal system digestive system diseases Cell biology Apoptosis Unfolded protein response cardiovascular system Endoplasmic reticulum stress Intracellular Reports |
Zdroj: | BMB Reports |
ISSN: | 1976-670X 1976-6696 |
Popis: | Nucleotide-binding oligomerization domain protein 2 (NOD2), an intracellular pattern recognition receptor, plays important roles in inflammation and cell death. Previously, we have shown that NOD2 is expressed in vascular smooth muscle cells (VSMCs) and that NOD2 deficiency promotes VSMC proliferation, migration, and neointimal formation after vascular injury. However, its role in endoplasmic reticulum (ER) stress-induced cell death in VSMCs remains unclear. Thus, the objective of this study was to evaluate ER stress-induced viability of mouse primary VSMCs. NOD2 deficiency increased ER stress-induced cell death and expression levels of apoptosis mediators (cleaved caspase-3, Bax, and Bak) in VSMCs in the presence of tunicamycin (TM), an ER stress inducer. In contrast, ER stress-induced cell death and expression levels of apoptosis mediators (cleaved caspase-3, Bax, and Bak) were decreased in NOD2-overexpressed VSMCs. We found that the IRE-1α-XBP1 pathway, one of unfolded protein response branches, was decreased in NOD2-deficient VSMCs and reversed in NOD2-overexpressed VSMCs in the presence of TM. Furthermore, NOD2 deficiency reduced the expression of XBP1 target genes such as GRP78, PDI-1, and Herpud1, thus improving cell survival. Taken together, these data suggest that the induction of ER stress through NOD2 expression can protect against TM-induced cell death in VSMCs. These results may contribute to a new paradigm in vascular homeostasis. [BMB Reports 2019; 52(11): 665-670]. |
Databáze: | OpenAIRE |
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