The AMPK enzyme-complex: from the regulation of cellular energy homeostasis to a possible new molecular target in the management of chronic inflammatory disorders

被引:44
作者
Antonioli, Luca [1 ]
Colucci, Rocchina [1 ]
Pellegrini, Carolina [1 ]
Giustarini, Giulio [1 ]
Sacco, Deborah [1 ]
Tirotta, Erika [1 ]
Caputi, Valentina [2 ]
Marsilio, Ilaria [2 ]
Giron, Maria Cecilia [2 ]
Nemeth, Zoltan H. [3 ,4 ]
Blandizzi, Corrado [1 ]
Fornai, Matteo [1 ]
机构
[1] Univ Pisa, Dept Clin & Expt Med, Via Roma 55, I-56126 Pisa, Italy
[2] Univ Padua, Dept Pharmaceut & Pharmacol Sci, Padua, Italy
[3] Morristown Med Ctr, Dept Surg, Morristown, NJ USA
[4] Rutgers New Jersey Med Sch, Dept Surg, Newark, NJ USA
关键词
macrophages; inflammatory disease; neutrophils; lymphocytes; adenosine triphosphate; adenosine; inflammation; immune system; adenosine monophosphate-activated protein kinase; dendritic cells; ACTIVATED PROTEIN-KINASE; KAPPA-B PATHWAY; IN-VIVO; 5-AMINOIMIDAZOLE-4-CARBOXAMIDE RIBONUCLEOSIDE; RHEUMATOID-ARTHRITIS; DEFICIENT MICE; T-LYMPHOCYTES; SIGNALING PATHWAYS; ENDOTHELIAL-CELLS; GLYCOGEN-SYNTHASE;
D O I
10.1517/14728222.2016.1086752
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: Adenosine monophosphate-activated protein kinase (AMPK), known as an enzymatic complex that regulates the energetic metabolism, is emerging as a pivotal enzyme and enzymatic pathway involved in the regulation of immune homeostatic networks. It is also involved in the molecular mechanisms underlying the pathophysiology of chronic inflammatory diseases. Areas covered: AMPK is expressed in several immune cell types including macrophages, lymphocytes, neutrophils and dendritic cells, and governs a broad array of cell functions, which include cytokine production, chemotaxis, cytotoxicity, apoptosis and proliferation. Based on its wide variety of immunoregulatory actions, the AMPK system has been targeted to reveal its impact on the course of immune-related diseases, such as atherosclerosis, psoriasis, joint inflammation and inflammatory bowel diseases. Expert opinion: The identification of AMPK subunits responsible for specific anti-inflammatory actions and the understanding of the underlying molecular mechanisms will promote the generation of novel AMPK activators, endowed with improved pharmacodynamic and pharmacokinetic profiles. These new tools will aid us to utilize AMPK pathway activation in the management of acute and chronic inflammatory diseases, while minimizing potential adverse reactions related to the effects of AMPK on metabolic energy.
引用
收藏
页码:179 / 191
页数:13
相关论文
共 103 条
  • [1] The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways
    Ahn, Jiyun
    Lee, Hyunjung
    Kim, Suna
    Park, Jaeho
    Ha, Taleyoul
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2008, 373 (04) : 545 - 549
  • [2] Epidemiology of adult rheumatoid arthritis
    Alamanos, Y
    Drosos, AA
    [J]. AUTOIMMUNITY REVIEWS, 2005, 4 (03) : 130 - 136
  • [3] Stimulators of AMP-activated protein kinase inhibit the respiratory burst in human neutrophils
    Alba, G
    El Bekay, R
    Alvarez-Maqueda, M
    Chacón, P
    Vega, A
    Monteseirín, J
    María, CS
    Pintado, E
    Bedoya, FJ
    Bartrons, R
    Sobrino, F
    [J]. FEBS LETTERS, 2004, 573 (1-3): : 219 - 225
  • [4] A role of DNA-dependent protein kinase for the activation of AMP-activated protein kinase in response to glucose deprivation
    Amatya, Parmeshwar Narayan
    Kim, Hong-Beum
    Park, Seon-Joo
    Youn, Cha-Kyung
    Hyun, Jin-Won
    Chang, In-Youb
    Lee, Jung-Hee
    You, Ho Jin
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2012, 1823 (12): : 2099 - 2108
  • [5] AMP-activated protein kinase enhances the phagocytic ability of macrophages and neutrophils
    Bae, Hong-Beom
    Zmijewski, Jaroslaw W.
    Deshane, Jessy S.
    Tadie, Jean-Marc
    Chaplin, David D.
    Takashima, Seiji
    Abraham, Edward
    [J]. FASEB JOURNAL, 2011, 25 (12) : 4358 - 4368
  • [6] AMPK agonist downregulates innate and adaptive immune responses in TNBS-induced murine acute and relapsing colitis
    Bai, Aiping
    Ma, Allan G.
    Yong, Michael
    Weiss, Carolyn R.
    Ma, Yanbing
    Guan, Qingdong
    Bernstein, Charles N.
    Peng, Zhikang
    [J]. BIOCHEMICAL PHARMACOLOGY, 2010, 80 (11) : 1708 - 1717
  • [7] Novel Anti-Inflammatory Action of 5-Aminoimidazole-4-carboxamide Ribonucleoside with Protective Effect in Dextran Sulfate Sodium-Induced Acute and Chronic Colitis
    Bai, Aiping
    Yong, Michael
    Ma, Allan G.
    Ma, Yanbing
    Weiss, Carolyn R.
    Guan, Qingdong
    Bernstein, Charles N.
    Peng, Zhikang
    [J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2010, 333 (03) : 717 - 725
  • [8] Immunobiology of dendritic cells
    Banchereau, J
    Briere, F
    Caux, C
    Davoust, J
    Lebecque, S
    Liu, YT
    Pulendran, B
    Palucka, K
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 2000, 18 : 767 - +
  • [9] AMPKα1-Sensitivity of Orai1 and Ca2+ Entry in T-Lymphocytes
    Bhavsar, Shefalee K.
    Schmidt, Sebastian
    Bobbala, Diwakar
    Nurbaeva, Meerim K.
    Hosseinzadeh, Zohreh
    Merches, Katja
    Fajol, Abul
    Wilmes, Jan
    Lang, Florian
    [J]. CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2013, 32 (03) : 687 - 698
  • [10] LKB1 and AMPK: central regulators of lymphocyte metabolism and function
    Blagih, Julianna
    Krawczyk, Connie M.
    Jones, Russell G.
    [J]. IMMUNOLOGICAL REVIEWS, 2012, 249 : 59 - 71