p38 Mitogen-activated protein kinase is involved in endoplasmic reticulum stress-induced cell death and autophagy in human gingival fibroblasts.
Inflammation or hypoxia in gingival tissue can induce endoplasmic reticulum (ER) stress, which is related with autophagy. The autophagy is a catabolic process involving the degradation of a cell's own components. Although autophagy resulting in the total destruction of the cell is one of cell death types, no conclusive evidence exists for such a process. In order to examine the association of ER stress and autophagy in gingival system, ER stress agents brefeldin A, thapsigargin, and tunicamycin were exposed to human gingival cells. The ER stress agents induced cell death and the expression of ER stress proteins, glucose-regulated protein of 78 kDa (GRP78) and CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP). ER stress also increased the formation of autophagic vesicles with the expression of beclin and LC-3 (microtubule-associated protein1 light chain 3) II, two autophagic markers. ER stress induced the phosphorylation of p38MAPK (mitogen-activated protein kinase), and the p38MPAK inhibitor, SB203580, inhibited the resulting cell death and autophagy. In summary, ER stress induces cell death and autophagy through p38MAPK in human gingival cells.
Kim
Do-Sung
DS
Department of Pharmacology and Institute of Cardiovascular Research, School of Medicine, Chonbuk National University, Korea.
Kim
Jung-Hoon
JH
Lee
Geum-Hwa
GH
Kim
Hyung-Tae
HT
Lim
Jung Min
JM
Chae
Soo-Wan
SW
Chae
Han-Jung
HJ
Kim
Hyung-Ryong
HR
D001343:Autophagy / Q000187:drug effects; D020126:Brefeldin A / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D004791:Enzyme Inhibitors; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005881:Gingiva / Q000187:drug effects / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010766:Phosphorylation; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011725:Pyridines; D019284:Thapsigargin / Q000494:pharmacology; D051742:Transcription Factor CHOP / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000091342:Endoplasmic Reticulum Chaperone BiP; D004791:Enzyme Inhibitors; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D007093:Imidazoles; D008869:Microtubule-Associated Proteins; D011500:Protein Synthesis Inhibitors; D011725:Pyridines; D014415:Tunicamycin; D051742:Transcription Factor CHOP; D020126:Brefeldin A; D019284:Thapsigargin; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580