PKD prevents H2O2-induced apoptosis via NF-kappaB and p38 MAPK in RIE-1 cells.
Previously, we demonstrated that protein kinase D (PKD) plays a protective role during H(2)O(2)-induced intestinal cell death. Here, we sought to determine whether this effect is mediated by nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinases (MAPKs). Treatment with H(2)O(2) activated NF-kappaB in RIE-1 cells; H(2)O(2) also induced the translocation of NF-kappaB p65 as well as phosphorylation of IkappaB-alpha. PKD1 siRNA inhibited H(2)O(2)-induced activation, translocation of NF-kappaB, and phosphorylation of IkappaB-alpha. We also found that overexpression of wild type PKD1 attenuated H(2)O(2)-induced phosphorylation of p38 MAPK and its upstream activator, MAPK kinase (MKK) 3/6, whereas the phosphorylation was increased by PKD1 siRNA or kinase-dead PKD1. Phosphorylation of neither extracellular signal-regulated kinases (ERK) 1/2 nor c-Jun N-terminal kinases (JNK) was altered by PKD1 plasmids or siRNA. Our findings suggest that PKD protects intestinal cells through up-regulation of NF-kappaB and down-regulation of p38 MAPK.
Song
Jun
J
Department of Surgery, The University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0353, USA.
Li
Jing
J
Qiao
Jingbo
J
Jain
Sunil
S
Mark Evers
B
B
Chung
Dai H
DH
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D004789:Enzyme Activation; D006861:Hydrogen Peroxide / Q000633:toxicity; D020672:I-kappa B Proteins / Q000378:metabolism; D007422:Intestines / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D048371:MAP Kinase Kinase 3 / Q000378:metabolism; D048669:MAP Kinase Kinase 6 / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000502:physiology*; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D051996:Transcription Factor RelA / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D020672:I-kappa B Proteins; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; D006861:Hydrogen Peroxide; C089212:protein kinase D; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D048371:MAP Kinase Kinase 3; D048669:MAP Kinase Kinase 6