PMID- 16179588 OWN - NLM STAT- MEDLINE DCOM- 20051207 LR - 20220228 IS - 1524-4571 (Electronic) IS - 0009-7330 (Linking) VI - 97 IP - 9 DP - 2005 Oct 28 TI - AMP-activated protein kinase activates p38 mitogen-activated protein kinase by increasing recruitment of p38 MAPK to TAB1 in the ischemic heart. PG - 872-9 AB - AMP-activated protein kinase (AMPK) promotes glucose transport, maintains ATP stores, and prevents injury and apoptosis during ischemia. AMPK has several direct molecular targets in the heart but also may interact with other stress-signaling pathways. This study examined the role of AMPK in the activation of the p38 mitogen-activated protein kinase (MAPK). In isolated heart muscles, the AMPK activator 5-aminoimidazole-4-carboxy-amide-1-beta-D-ribofuranoside (AICAR) increased p38 MAPK activation. In AMPK-deficient mouse hearts, expressing a kinase-dead (KD) alpha2 catalytic subunit, p38 MAPK activation was markedly reduced during low-flow ischemia (2.3- versus 7-fold in wild-type hearts, P<0.01) and was similarly reduced during severe no-flow ischemia in KD hearts (P<0.01 versus ischemic wild type). Knockout of the p38 MAPK upstream kinase, MAPK kinase 3 (MKK3), did not affect ischemic activation of either AMPK or p38 MAPK in transgenic mkk3(-/-) mouse hearts. Ischemia increased p38 MAPK recruitment to transforming growth factor-beta-activated protein kinase 1-binding protein 1 (TAB1), a scaffold protein that promotes p38 MAPK autophosphorylation. Moreover, TAB1 was associated with the alpha2 catalytic subunit of AMPK. p38 MAPK recruitment to TAB1/AMPK complexes required AMPK activation and was reduced in ischemic AMPK-deficient transgenic mouse hearts. The potential role of p38 MAPK in mediating the downstream action of AMPK to promote glucose transport was also assessed. The p38 MAPK inhibitor SB203580 partially inhibited both AICAR- and hypoxia-stimulated glucose uptake and GLUT4 translocation. Activation of p38 MAPK by anisomycin also increased glucose transport in heart muscles. Thus, AMPK has an important role in promoting p38 MAPK activation in the ischemic heart by inducing p38 MAPK autophosphorylation through interaction with the scaffold protein TAB1. FAU - Li, Ji AU - Li J AD - Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. FAU - Miller, Edward J AU - Miller EJ FAU - Ninomiya-Tsuji, Jun AU - Ninomiya-Tsuji J FAU - Russell, Raymond R 3rd AU - Russell RR 3rd FAU - Young, Lawrence H AU - Young LH LA - eng GR - R01 HL63811/HL/NHLBI NIH HHS/United States GR - T32 HL07950/HL/NHLBI NIH HHS/United States GR - U24 DK59635/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, P.H.S. DEP - 20050922 PL - United States TA - Circ Res JT - Circulation research JID - 0047103 RN - 0 (Glucose Transporter Type 4) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Multienzyme Complexes) RN - 0 (Ribonucleotides) RN - 0 (TAB1 protein, MAPKKK activator, vertebrate) RN - 360-97-4 (Aminoimidazole Carboxamide) RN - 6C74YM2NGI (Anisomycin) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - EC 2.7.12.2 (MAP Kinase Kinase 3) RN - EC 2.7.12.2 (Map2k3 protein, mouse) RN - F0X88YW0YK (AICA ribonucleotide) RN - IY9XDZ35W2 (Glucose) SB - IM MH - AMP-Activated Protein Kinases MH - Aminoimidazole Carboxamide/analogs & derivatives/pharmacology MH - Animals MH - Anisomycin/pharmacology MH - Cell Hypoxia MH - Enzyme Activation MH - Glucose/metabolism MH - Glucose Transporter Type 4/metabolism MH - Intracellular Signaling Peptides and Proteins/*metabolism MH - MAP Kinase Kinase 3/physiology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Multienzyme Complexes/*physiology MH - Myocardial Ischemia/*enzymology MH - Protein Serine-Threonine Kinases/*physiology MH - Protein Transport MH - Rats MH - Rats, Sprague-Dawley MH - Ribonucleotides/pharmacology MH - p38 Mitogen-Activated Protein Kinases/*metabolism EDAT- 2005/09/24 09:00 MHDA- 2005/12/13 09:00 CRDT- 2005/09/24 09:00 PHST- 2005/09/24 09:00 [pubmed] PHST- 2005/12/13 09:00 [medline] PHST- 2005/09/24 09:00 [entrez] AID - 01.RES.0000187458.77026.10 [pii] AID - 10.1161/01.RES.0000187458.77026.10 [doi] PST - ppublish SO - Circ Res. 2005 Oct 28;97(9):872-9. doi: 10.1161/01.RES.0000187458.77026.10. Epub 2005 Sep 22.