본문 바로가기
KERD
논문KCI 등재

Oxidized LDL induces phosphorylation of non-muscle myosin IIA heavy chain in macrophages

1

조회

0

다운로드

2

인용

0

참고문헌

키워드

주제분류화학

초록

Oxidized LDL (oxLDL) performs critical roles in atherosclerosisby inducing macrophage foam cell formation and promotinginflammation. There have been reports showing that oxLDLmodulates macrophage cytoskeletal functions for oxLDLuptake and trapping, however, the precise mechanism has notbeen clearly elucidated. Our study examined the effect ofoxLDL on non-muscle myosin heavy chain IIA (MHC-IIA) inmacrophages. We demonstrated that oxLDL induces phosphorylationof MHC-IIA (Ser1917) in peritoneal macrophages fromwild-type mice and THP-1, a human monocytic cell line, butnot in macrophages deficient for CD36, a scavenger receptorfor oxLDL. Protein kinase C (PKC) inhibitor-treated macrophagesdid not undergo the oxLDL-induced MHC-IIA phosphorylation. Our immunoprecipitation revealed that oxLDLincreased physical association between PKC and MHC-IIA,supporting the role of PKC in this process. We conclude thatoxLDL via CD36 induces PKC-mediated MHC-IIA (Ser1917)phosphorylation and this may affect oxLDL-induced functionsof macrophages involved in atherosclerosis.

Abstract

Oxidized LDL (oxLDL) performs critical roles in atherosclerosisby inducing macrophage foam cell formation and promotinginflammation. There have been reports showing that oxLDLmodulates macrophage cytoskeletal functions for oxLDLuptake and trapping, however, the precise mechanism has notbeen clearly elucidated. Our study examined the effect ofoxLDL on non-muscle myosin heavy chain IIA (MHC-IIA) inmacrophages. We demonstrated that oxLDL induces phosphorylationof MHC-IIA (Ser1917) in peritoneal macrophages fromwild-type mice and THP-1, a human monocytic cell line, butnot in macrophages deficient for CD36, a scavenger receptorfor oxLDL. Protein kinase C (PKC) inhibitor-treated macrophagesdid not undergo the oxLDL-induced MHC-IIA phosphorylation. Our immunoprecipitation revealed that oxLDLincreased physical association between PKC and MHC-IIA,supporting the role of PKC in this process. We conclude thatoxLDL via CD36 induces PKC-mediated MHC-IIA (Ser1917)phosphorylation and this may affect oxLDL-induced functionsof macrophages involved in atherosclerosis.

참고문헌 (50)

  1. Steinbrerg D, "Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity", N Engl J Med, 320, pp.915~924 (1989)
  2. Steinbrecher UP, "oxidation of human low density lipoprotein results in derivatization of lysine residues of apolipoprotein B by lipid peroxide decomposition products", J Biol Chem, 262, pp.3603~3608 (1987)
  3. Stocker R, "New insights on oxidative stress in the artery wall", J Throm Haem, 3, pp.1825~1834 (2005)
  4. Stocker R, "Role of oxidative modifications in atherosclerosis", Physiol Rev, 84, pp.1381~1478 (2004)
  5. Rajavashisth TB, "Induction of endothelial cell expression of granulocyte and macrophage colony-stimulating factors by modified low density lipoproteins", Nature (London), 344, pp.254~257 (1990)
  6. Cushing SD, "Minimally modified low density lipoprotein inducesmonocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells", Proc Natl Acad Sci U S A, 87, pp.5134~5138 (1990)
  7. Carlos TM, "Membrane proteins involved in phagocyte adherence to endothelium", Immunol Rev, 114, pp.5~28 (1990)
  8. Khan BV, "Modified low density lipoprotein and its constituents augment cytokine-activated vascular cell adhesion molecule-1 gene expression in human vascular endothelial cells", J Clin Invest, 95, pp.1262~1270 (1995)
  9. Chatterjee S, "Oxidized low density lipoprotein stimulates aortic smooth muscle cell proliferation", Glycobiology, 6, pp.303~311 (1996)
  10. Brown MS, "Atherosclerosis. Scavenging for receptors", Nature, 343, pp.508~509 (1990)
  11. Salonen JT, "Lipoprotein oxidation and progression of carotid atherosclerosis", Circulation, 95, pp.840~845 (1997)
  12. Duden R, "What's new in cytoskeleton-organelle interactions? Relationship between microtubules and the Golgi-apparatus", Pathol Res Pract, 186, pp.535~541 (1990)
  13. Zhao B, "Oxidized low-density lipoprotein increases endothelial intracellular calcium and alters cytoskeletal f-actin distribution", Eur J Clin Invest, 27, pp.48~54 (1997)
  14. Chouinard JA, "Oxidized-LDL induce morphological changes and increase stiffness of endothelial cells", Exp Cell Res, 314, pp.3007~3016 (2008)
  15. Chow S, "Oxidized LDL promotes vascular endothelial cell pinocytosis via a prooxidation mechanism", FASEB J, 12, pp.823~830 (1998)
  16. Miller YI, "Actin polymerization in macrophages in response to oxidized LDL and apoptotic cells: Role of 12", 15-Lipoxygenase and Phosphoinositide 3-Kinase, 2003, pp.14, 4196~4206
  17. Park YM, "CD36modulates migration of mouse and human macrophages in response to oxidized LDL and may contribute to macrophage trapping in the arterial intima", J Clin Invest, 119, pp.136~145 (2009)
  18. Park YM, "Oxidized LDL", CD36 interaction induces loss of cell polarity and inhibits macrophage locomotion, 2012, pp.23, 3057~3068
  19. Clark K, "Myosin II and mechanotransduction: a balancing act", Trends Cell Biol, 17, pp.178~186 (2007)
  20. Conti MA, "Nonmuscle myosin II moves in new directions", J Cell Sci, 121, pp.11~18 (2008)
  21. Vicente-Manzanares M, "Regulation of protrusion, adhesion dynamics, and polarity by myosin IIA and IIB in migrating cells", J Cell Biol, 176, pp.573~580 (2007)
  22. Choi CK, "Actin and α-actinin orchestrate the assembly and maturation of nascent adhesions in a myosin II motor-independent manner", Nat Cell Biol, 10, pp.1039~1050 (2008)
  23. Rosado LA, "Association between α4 integrin cytoplasmic tail and non-muscle myosin IIA regulates cell migration", J Cell Sci, 124, pp.483~492 (2011)
  24. Kim JH, "Nonmuscle myosin II is required for internalization of the epidermal growth factor receptor and modulation of downstream signaling", J Biol Chem, 287, pp.27345~27358 (2012)
  25. Kumari S, "T lymphocyte myosin IIA is required for maturation of the immunological synapse", Front Immunol, 3 (2012)
  26. Somlyo AP, "Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase", Physiol Rev, 83, pp.1325~1358 (2008)
  27. Dulyaninova NG, "Myosin-IIA heavy-chain phosphorylation regulates the motility of MDA-MB-231 carcinoma cells", Mol Biol Cell, 18, pp.3144~3155 (2007)
  28. Straussman R, "Myosin II heavy chain isoforms are phosphorylated in an EGF-dependent manner: involvement of protein kinase C", J Cell Sci, 114, pp.3047~3057 (2001)
  29. Ludowyke RI, "Phosphorylation of nonmuscle myosin heavy chain IIA on Ser1917 is mediated by protein kinase C beta II and coincides with the onset of stimulated degranulation of RBL-2H3 mast cells", J Immunol, 177, pp.1492~1499 (1917)
  30. Matsumura T, "Two intracellular signaling pathways for activation of protein kinase C are involved in oxidized low-density lipoprotein-induced macrophage growth", Arterioscler Thromb Vasc Biol, 17, pp.3013~3020 (1997)
  31. Feng J, "Induction of CD36expression by oxidized LDL and IL-4 by a common signaling pathway dependent on protein kinase C and PPAR-γ", J Lipid Res, 41, pp.688~696 (2000)
  32. Witzum JL, "The oxidative modification hypothesis of atherosclerosis: Does it hold for humans?", Trends Cardiovasc Med, 11, pp.93~102 (2001)
  33. Yla-Herttuala S, "Is oxidized low-density lipoprotein present in vivo?", Curr Opin Lipidol, 9, pp.337~344 (1998)
  34. Itabe H, "Sensitive detection of oxidatively modified low density lipoprotein using a monoclonal antibody", J Lipid Res, 37, pp.45~53 (1996)
  35. Tsimikas S, "Oxidative biomarkers in the diagnosis and prognosis of cardiovascular disease", Am J cardiol, 98, pp.9~17 (2006)
  36. Silverstein RL, "Mechanisms of cell signaling by the scavenger receptor CD36; Implications in atherosclerosis and thrombosis", Trans Am Clin Climatol Assoc, 121, pp.206~220 (2010)
  37. 박영미, "CD36, a scavenger receptor implicated in atherosclerosis", Experimental and Molecular Medicine, 46, pp.1~7 (2014), 생화학분자생물학회
  38. Rahaman SO, "A CD36-dependent signaling cascade is necessary for macrophage foam cell formation", Cell Metab, 4, pp.211~221 (2006)
  39. Collins RF, "Uptake of oxidized low density lipoprotein by CD36 occurs by an actin-dependent pathway distinct from macropinocytosis", J Biol Chem, 284, pp.30288~30297 (2009)
  40. Jones NL, "Modified LDLs are internalized by macrophages in part via macropinocytosis", Anat Rec, 255, pp.57~68 (1999)
  41. Zeng Y, "Endocytosis of oxidized low density lipoprotein through scavenger receptor CD36 utilizes a lipid raft pathway that does not require caveolin-1", J Biol Chem, 278, pp.45931~45936 (2003)
  42. Sun B, "Distinct mechanisms for OxLDL uptake and cellular trafficking by class B scavenger receptors CD36 and SR-BI", J Lipid Res, 48, pp.2560~2570 (2007)
  43. Even-Faitelson L, "PAK1 and aPKCzeta regulate myosin II-B phosphorylation: a novel signaling pathway regulating filament assembly", Mol Biol Cell, 17, pp.2869~2881 (2006)
  44. Dulyaninova NG, "Regulation of myosin-IIA assembly and Mts1 binding by heavy chain phosphorylation", Biochemistry, 44, pp.6867~6876 (2005)
  45. Clark K, "TRPM7 regulates myosin IIA filament stability and protein localization by heavy chain phosphorylation", J Mol Biol, 378, pp.790~803 (2008)
  46. Bajaj G, "N-methyl-d-aspartate receptor subunits are non-myosin targets of myosin regulatory light chain", J Biol Chem, 284, pp.1252~1266 (2009)
  47. Hours MC, "The N-terminal domain of the type 1 Ins(1, 4, 5)P3 receptor stably expressed in MDCK cells interacts with myosin IIA and alters epithelial cell morphology", J Cell Sci, 123, pp.1449~1459 (2010)
  48. Huang Y, "The collagen receptor DDR1 regulates cell spreading and motility by associating with myosin IIA", J Cell Sci, 122, pp.1637~1646 (2009)
  49. Rey M, "Myosin IIA is involved in the endocytosis of CXCR4 induced by SDF-1α", J Cell Sci, 120, pp.1126~1233 (2007)
  50. Hatch FT, "Practical methods for plasma lipoprotein analysis", Adv Lipid Res, 6, pp.1~68 (1968)

관련 논문AI추천

이 간행물의 다른 논문 (9건)