Pyruvate Dehydrogenase Kinase 4 Promotes Vascular Calcification via SMAD1/5/8 Phosphorylation

Scientific Reports

Volumn 5, Issue , 2015, Pages

  Lee, Sun Joo ^a   Jeong, Ji Yun ^b,i   Oh, Chang Joo ^b   Park, Sungmi ^b   Kim, Joon Young ^b,j   Kim, Han Jong ^b,k   Doo Kim, Nam ^c   Choi, Young Keun ^b   Do, Ji Yeon ^b   Go, Younghoon ^b   Ha, Chae Myung ^b   Choi, Je Yong ^b   Huh, Seung ^b   Ho Jeoung, Nam ^d   Lee, Ki Up ^e   Choi, Hueng Sik ^f   Wang, Yu ^g   Park, Keun Gyu ^b   Harris, Robert A ^h   Lee, In Kyu ^b  

^a Kyungpook National University School of Medicine   (South Korea)

^b Kyungpook National University   (South Korea)

^c Daegu Gyeongbuk Medical Innovation Foundation   (South Korea)

^d Catholic University of Daegu   (South Korea)

^e University of Ulsan College of Medicine   (South Korea)

^f Chonnam National University   (South Korea)

^g UNIVERSITY OF HONG KONG   (Hong Kong)

^h INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

ⁱ Soonchunhyang University   (South Korea)

^j Gwangju Institute of Science and Technology (GIST)   (South Korea)

^k Chonnam National University Research Institute of Medical Sciences   (South Korea)

more..

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; PROTEIN BINDING; PROTEIN KINASE; PROTEIN KINASE INHIBITOR; PYRUVATE DEHYDROGENASE KINASE 4; SMAD1 PROTEIN; SMAD5 PROTEIN; SMAD8 PROTEIN;

ANIMAL; APOPTOSIS; BLOOD VESSEL CALCIFICATION; BONE DEVELOPMENT; BONE REMODELING; CELL CULTURE; CELL DIFFERENTIATION; CHEMISTRY; CYTOLOGY; DISEASE MODEL; GENE EXPRESSION; GENE SILENCING; GENETICS; HUMAN; KNOCKOUT MOUSE; MALE; METABOLISM; MITOCHONDRION; MOUSE; PHOSPHORYLATION; SMOOTH MUSCLE CELL; VASCULAR SMOOTH MUSCLE;

ANIMALS; APOPTOSIS; BIOMARKERS; BONE REMODELING; CELL DIFFERENTIATION; CELLS, CULTURED; DISEASE MODELS, ANIMAL; GENE EXPRESSION; GENE KNOCKDOWN TECHNIQUES; HUMANS; MALE; MICE; MICE, KNOCKOUT; MITOCHONDRIA; MUSCLE, SMOOTH, VASCULAR; MYOCYTES, SMOOTH MUSCLE; OSTEOGENESIS; PHOSPHORYLATION; PROTEIN BINDING; PROTEIN KINASE INHIBITORS; PROTEIN KINASES; SMAD1 PROTEIN; SMAD5 PROTEIN; SMAD8 PROTEIN; VASCULAR CALCIFICATION;

EID: 84946897446     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep16577     Document Type: Article

References (53)

1. Raggi, P. et al. Cardiac calcification in adult hemodialysis patients. A link between end-stage renal disease and cardiovascular disease? J. Am. Coll. Cardiol. 39, 695-701, doi: 10.1016/S0735-1097(01)01781-8 (2002).
2. Raggi, P., Shaw, L. J., Berman, D. S. & Callister, T. Q. Prognostic value of coronary artery calcium screening in subjects with and without diabetes. J. Am. Coll. Cardiol. 43, 1663-1669, doi: 10.1016/j.jacc.2003.09.068 (2004).
3. Wilson, P. W. F. et al. Abdominal Aortic Calcific Deposits Are an Important Predictor of Vascular Morbidity and Mortality. Circulation 103, 1529-1534, doi: 10.1161/01.cir.103.11.1529 (2001).
4. Derwall, M. et al. Inhibition of bone morphogenetic protein signaling reduces vascular calcification and atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 32, 613-622, doi: 10.1161/ATVBAHA.111.242594 (2012).
5. Hruska, K. A., Mathew, S. & Saab, G. Bone morphogenetic proteins in vascular calcification. Circ. Res. 97, 105-114, doi: 10.1161/01.RES.00000175571.53833.6c (2005).
6. Moe, S. M. & Chen, N. X. Pathophysiology of vascular calcification in chronic kidney disease. Circ. Res. 95, 560-567, doi: 10.1161/01.res.0000141775.67189.98 (2004).
7. Han, M.-S. et al. Functional Cooperation between Vitamin D Receptor and Runx2 in Vitamin D-Induced Vascular Calcification. PLoS ONE 8, e83584, doi: 10.1371/journal.pone.0083584 (2013).
8. Leu, M. & Giovannucci, E. Vitamin D: epidemiology of cardiovascular risks and events. Best Pract Res Clin Endocrinol Metab. 25, 633-46, doi: 10.1016/j.beem.2011.04.001 (2011)
9. Lau, W. L., Pai, A., Moe, S. M. & Giachelli, C. M. Direct effects of phosphate on vascular cell function. Adv. Chronic Kidney Dis. 18, 105-112, doi: 10.1053/j.ackd.2010.12.002 (2011).
10. Cai, J., Pardali, E., Sanchez-Duffhues, G. & ten Dijke, P. BMP signaling in vascular diseases. FEBS Lett 586, 1993-2002, doi: 10.1016/j.febslet.2012.04.030 (2012).
11. Tyson, K. L. et al. Osteo/chondrocytic transcription factors and their target genes exhibit distinct patterns of expression in human arterial calcification. Arterioscler. Thromb. Vasc. Biol. 23, 489-494, doi: 10.1161/01.ATV.0000059406.92165.31 (2003).
12. Lee, K. S. et al. Runx2 is a common target of transforming growth factor beta1 and bone morphogenetic protein 2, and cooperation between Runx2 and Smad5 induces osteoblast-specific gene expression in the pluripotent mesenchymal precursor cell line C2C12. Mol. Cell. Biol. 20, 8783-8792, doi: 10.1128/MCB.20.23.8783-8792.2000 (2000).
13. Sun, Y. et al. Smooth muscle cell-specific runx2 deficiency inhibits vascular calcification. Circ. Res. 111, 543-552, doi: 10.1161/CIRCRESAHA.112.267237 (2012).
14. Komori, T. et al. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89, 755-764, doi: 10.1016/S0092-8674(00)80258-5 (1997).
15. Harris, R. A., Bowker-Kinley, M. M., Huang, B. & Wu, P. Regulation of the activity of the pyruvate dehydrogenase complex. Adv. Enzyme Regul. 42, 249-259, doi: 10.1016/S0065-2571(01)00061-9 (2002).
16. Jeoung, N. H. & Harris, R. A. Pyruvate dehydrogenase kinase-4 deficiency lowers blood glucose and improves glucose tolerance in diet-induced obese mice. Am. J. Physiol. Endocrinol. Metab. 295, E46-54, doi: 10.1152/ajpendo.00536.2007 (2008).
17. Jeong, J. Y., Jeoung, N. H., Park, K. G. & Lee, I. K. Transcriptional regulation of pyruvate dehydrogenase kinase. Diabetes Metab. J. 36, 328-335, doi: 10.4093/dmj.2012.36.5.328 (2012).
18. Mori, K., Shioi, A., Jono, S., Nishizawa, Y. & Morii, H. Dexamethasone enhances in vitro vascular calcification by promoting osteoblastic differentiation of vascular smooth muscle cells. Arterioscler. Thromb. Vasc. Biol. 19, 2112-2118, doi: 10.1161/01.ATV.19.9.2112 (1999).
19. Huang, B., Wu, P., Bowker-Kinley, M. M. & Harris, R. A. Regulation of pyruvate dehydrogenase kinase expression by peroxisome proliferator-activated receptor-α ligands, glucocorticoids, and insulin. Diabetes 51, 276-283, doi: 10.2337/diabetes.51.2.276 (2002).
20. Prosdocimo, D. A., Wyler, S. C., Romani, A. M., O'Neill, W. C. & Dubyak, G. R. Regulation of vascular smooth muscle cell calcification by extracellular pyrophosphate homeostasis: synergistic modulation by cyclic AMP and hyperphosphatemia. Am. J. Physiol. Cell. Physiol. 298, C702-C713, doi: 10.1152/ajpcell.00419.2009 (2010).
21. +. Mol. cell 44, 851-863, doi: 10.1016/j.molcel.2011.12.005 (2011).
22. Armstrong, Z. B., Boughner, D. R., Drangova, M. & Rogers, K. A. Angiotensin II type 1 receptor blocker inhibits arterial calcification in a pre-clinical model. Cardiovasc. Res. 90, 165-170, doi: 10.1093/cvr/cvq391 (2011).
23. Mori, J. et al. ANG II causes insulin resistance and induces cardiac metabolic switch and inefficiency: a critical role of PDK4. Am. J. Physiol. Heart Circulatory Physiology 304, H1103-H1113, doi: 10.1152/ajpheart.00636.2012 (2013).
24. Hsu, J. J. et al. T0901317, an LXR agonist, augments PKA-induced vascular cell calcification. FEBS Letters 583, 1344-1348, doi: 10.1016/j.febslet.2009.03.039 (2009).
25. Paul, W. C., Mark, J. H., David, B.-B. & Mary, C. S. PPARalpha-LXR as a novel metabolostatic signalling axis in skeletal muscle that acts to optimize substrate selection in response to nutrient status. Biochem. J. 437, 521-530, doi: 10.1042/BJ20110702 (2011).
26. Wang, C. C., Sorribas, V., Sharma, G., Levi, M. & Draznin, B. Insulin attenuates vascular smooth muscle calcification but increases vascular smooth muscle cell phosphate transport. Atherosclerosis 195, e65-75, doi: 10.1016/j.atherosclerosis.2007.02.032 (2007).
27. Crewe, C., Kinter, M. & Szweda, L. I. Rapid inhibition of pyruvate dehydrogenase: an initiating event in high dietary fat-induced loss of metabolic flexibility in the heart. PloS ONE 8, e77280, doi: 10.1371/journal.pone.0077280 (2013).
28. Kolobova, E., Tuganova, A., Boulatnikov, I. & Popov, K. M. Regulation of pyruvate dehydrogenase activity through phosphorylation at multiple sites. Biochem. J. 358, 69-77, doi: 10.1042/bj3580069 (2001).
29. Sage, A. P., Tintut, Y. & Demer, L. L. Regulatory mechanisms in vascular calcification. Nature reviews. Cardiology 7, 528-536, doi: 10.1038/nrcardio.2010.115 (2010).
30. Price, P. A., June, H. H., Buckley, J. R. & Williamson, M. K. Osteoprotegerin inhibits artery calcification induced by warfarin and by vitamin D. Arterioscler. Thromb. Vasc. Biol. 21, 1610-1616, doi: 10.1161/hq1001.097102 (2001).
31. Kato, M., Li, J., Chuang, J. L. & Chuang, D. T. Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol. Structure 15, 992-1004, doi: 10.1016/j.str.2007.07.001 (2007).
32. Cai, J., Pardali, E., Sánchez-Duffhues, G. & ten Dijke, P. BMP signaling in vascular diseases. FEBS Letters 586, 1993-2002, doi: 10.1016/j.febslet.2012.04.030 (2012).
33. Jullig, M. & Stott, N. S. Mitochondrial localization of Smad5 in a human chondrogenic cell line. Biochem. Biophys. Res. Commun. 307, 108-113, doi: 10.1016/S0006-291X(03)01139-2 (2003).
34. Kim, S. et al. PDHK-2 Deficiency Is Associated with Attenuation of Lipase-Mediated Fat Consumption for the Increased Survival of Caenorhabditis elegans Dauers. PLoS ONE 7, e41755, doi: 10.1371/journal.pone.0041755 (2012).
35. Kretzschmar, M., Liu, F., Hata, A., Doody, J. & Massague, J. The TGF-beta family mediator Smad1 is phosphorylated directly and activated functionally by the BMP receptor kinase. Genes Dev. 11, 984-995, doi: 10.1101/gad.11.8.984 (1997).
36. Wynn, R. M. et al. Pyruvate dehydrogenase kinase-4 structures reveal a metastable open conformation fostering robust core-free basal activity. J. Biol. Chem. 283, 25305-25315, doi: 10.1074/jbc.M802249200 (2008).
37. Byon, C. H. et al. Oxidative stress induces vascular calcification through modulation of the osteogenic transcription factor Runx2 by AKT signaling. J. Biol. Chem. 283, 15319-15327, doi: 10.1074/jbc.M800021200 (2008).
38. Korotchkina, L. G., Sidhu, S. & Patel, M. S. R-lipoic acid inhibits mammalian pyruvate dehydrogenase kinase. Free radical research 38, 1083-1092, doi: 10.1080/10715760400004168 (2004).
39. Kim, H. et al. α -Lipoic acid attenuates vascular calcification via reversal of mitochondrial function and restoration of Gas6/Axl/Akt survival pathway. J. Cell Mol. Med. 16, 273-286, doi: 10.1111/j.1582-4934.2011.01294.x (2012).
40. Persy, V. & D'Haese, P. Vascular calcification and bone disease: the calcification paradox. Trends Mol. Med. 15, 405-416, doi: 10.1016/j.molmed.2009.07.001 (2009).
41. Wang, Y. et al. Pyruvate dehydrogenase kinase 4 induces bone loss at unloading by promoting osteoclastogenesis. Bone 50, 409-419, doi: 10.1016/j.bone.2011.07.012 (2012).
42. Chen, H. B., Shen, J., Ip, Y. T. & Xu, L. Identification of phosphatases for Smad in the BMP/DPP pathway. Gene Dev. 20, 648-653, doi: 10.1101/gad.1384706 (2006).
43. Narasimhan, S. D. et al. PDP-1 links the TGF-β and IIS pathways to regulate longevity, development, and metabolism. PLoS genetics 7, e1001377, doi: 10.1371/journal.pgen.1001377 (2011).
44. Kell, A., Ventura, N., Kahn, N. & Johnson, T. E. Activation of SKN-1 by novel kinases in Caenorhabditis elegans. Free Radic. Biol. Med. 43, 1560-1566, doi: 10.1016/j.freeradbiomed.2007.08.025 (2007).
45. Liu, Z. et al. PDK4 Protein Promotes Tumorigenesis through Activation of cAMP-response Element-binding Protein (CREB)-Ras Homolog Enriched in Brain (RHEB)-mTORC1 Signaling Cascade. J. Biol. Chem 289, 29739-29749, doi: 10.1074/jbc.M114.584821 (2014).
46. Idelevich, A., Rais, Y. & Monsonego-Ornan, E. Bone Gla Protein Increases HIF-1α -Dependent Glucose Metabolism and Induces Cartilage and Vascular Calcification. Arterioscler. Thromb. Vasc. Biol. 31, e55-e71, doi: 10.1161/atvbaha.111.230904 (2011).
47. Tsuji, K. et al. BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture healing. Nat. Genet. 38, 1424-1429, doi: 10.1038/ng1916 (2006).
48. Chappuis, V. et al. Periosteal BMP2 activity drives bone graft healing. Bone 51, 800-809, doi: 10.1016/j.bone.2012.07.017 (2012).
49. Khosla, S. The bone and beyond: a shift in calcium. Nat. Med. 17, 430-431, doi: 10.1038/nm0411-430 (2011).
50. Tankó, L. B. et al. Relationship Between Osteoporosis and Cardiovascular Disease in Postmenopausal Women. J. Bone Miner. Res. 20, 1912-1920, doi: 10.1359/jbmr.050711 (2005).
51. Ha, C. M. et al. Activation of Nrf2 by dimethyl fumarate improves vascular calcification. Vasc. Pharmacol. 63, 29-36, doi: 10.1016/j.vph.2014.06.007 (2014).
52. Jeoung, N. H. et al. Role of pyruvate dehydrogenase kinase isoenzyme 4 (PDHK4) in glucose homoeostasis during starvation. Biochem. J. 397, 417-425, doi: 10.1042/bj20060125 (2006).
53. Oldenburg, Olaf, et al. Bradykinin induces mitochondrial ROS generation via NO, cGMP, PKG, and mitoKATP channel opening and leads to cardioprotection. Am. J. Physiol. Heart Circ. Physiol. 286, H468-H476, doi: 10.1152/ajpheart.00360.200 (2004).