Inhibition of Poly-(ADP-Ribose) Polymerase Protects the Kidney in a Canine Model of Endotoxic Shock

被引:15
|
作者
Liu, Si-bo [1 ]
Liu, Jinjie [1 ,2 ]
Liu, Da-wei [3 ]
Wang, Xiao-ting [3 ]
Yang, Rong-li [1 ]
机构
[1] Dalian Municipal Cent Hosp, Surg Intens Care Unit, Dalian 116000, Shahekou Distri, Peoples R China
[2] Dalian Municipal Cent Hosp, VIP Ward 2, Dalian 116000, Shahekou Distri, Peoples R China
[3] Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Crit Care Med, Beijing 100021, Peoples R China
关键词
Acute kidney injury; Apoptosis; Endotoxic shock; Hemodynamics; PARP; 3-aminobenzamide; ADP-RIBOSE POLYMERASE; POLY(ADP-RIBOSE) POLYMERASE; CELL APOPTOSIS; BLOOD-FLOW; INJURY; PARP; 3-AMINOBENZAMIDE; SEPSIS;
D O I
10.1159/000435815
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Poly-(ADP-ribose) polymerases (PARPs), a super family of enzymes, play important roles in preserving genomic integrity, regulating transcriptions, protecting telomeres and determining cell fate. PARP overactivation leads to metabolic disorder and cell injury via depletion of energy substance. However, it is still unclear whether PARP overactivation happens during acute kidney injury (AKI) caused by endotoxic shock (ES). Here, we built a canine model of lipopolysaccharide-induced ES to explore the role of PARP during the development AKI. We also used an intravenous injection of 3-amino-benzamide (3-AB) to further explore whether PARP inhibition rescues the kidney from injury. Cell fate and energy metabolism were detected to explore the underlying mechanisms. As a result, Western blot and immunohistochemistry assays showed PARP overactivation in the very early phase of ES. Through PARP inhibition by 3-AB, we observed significant improvement of systemic hemodynamics, renal hemodynamics, renal oxygen metabolism and renal tubular cell apoptosis. These findings indicated that overactivation of PARP plays an important role in septic AKI. Inhibition of PARP overactivation may protect renal function against hemodynamic disorder, renal metabolism disturbance and renal cell apoptosis during endotoxic AKI. (C) 2015 S. Karger AG, Basel
引用
收藏
页码:281 / 292
页数:12
相关论文
共 50 条
  • [1] Inhibition of nuclear poly(ADP-ribose) polymerase protects the kidney from cytotoxic damage
    Rácz, IB
    Tory, K
    Jaszlits, L
    Rabloczky, G
    Bernath, S
    Sumegi, B
    Literati-Nagy, P
    JOURNAL OF PHYSIOLOGY-LONDON, 2000, 526 : 178P - 179P
  • [2] Inhibition of the activity of poly (ADP-ribose) polymerase in hemorrhagic shock
    McDonald, M
    Abdelrahman, M
    Mota-Filipe, H
    Cuzzocrea, S
    Thiemermann, C
    5TH WORLD CONGRESS ON TRAUMA, SHOCK, INFLAMMATION AND SEPSIS: PATHOPHYSIOLOGY, IMMUNE CONSEQUENCES AND THERAPY, 2000, : 355 - 359
  • [3] Inhibition of the activity of poly (ADP-ribose) polymerase in hemorrhagic shock
    McDonald, MC
    Mota-Filipe, H
    Abdelrahman, M
    Threadgill, M
    Thiemermann, C
    SHOCK, 2004, 21 : 91 - 91
  • [4] Apoptosis in the absence of poly-(ADP-ribose) polymerase
    Leist, M
    Single, B
    Kunstle, G
    Volbracht, C
    Hentze, H
    Nicotera, P
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1997, 233 (02) : 518 - 522
  • [5] Inactivation of constitutive nitric oxide synthase(s) and poly(ADP-ribose) polymerase protects brain against endotoxic shock
    Czapski, GA
    Cakala, M
    Strosznajder, JB
    JOURNAL OF NEUROCHEMISTRY, 2003, 87 : 133 - 133
  • [6] Inhibition of poly(ADP-ribose) polymerase by arsenite
    Yager, JW
    Wiencke, JK
    MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH, 1997, 386 (03) : 345 - 351
  • [7] Poly(ADP-ribose) polymerase:: Relevance for shock and inflammation
    Szabó, C
    SHOCK, 2004, 21 : 90 - 90
  • [8] Cardioprotective effects of poly (ADP-ribose) polymerase inhibition
    Szabó, C
    PHARMACOLOGICAL RESEARCH, 2005, 52 (01) : 34 - 43
  • [9] Poly(ADP-ribose)polymerase inhibition decreases angiogenesis
    Rajesh, Mohanraj
    Mukhopadhyay, Partha
    Godlewski, Grzegorz
    Batkai, Sandor
    Hasko, Gyorgy
    Liaudet, Lucas
    Pacher, Pal
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 350 (04) : 1056 - 1062
  • [10] Poly(ADP-ribose)polymerase inhibition - Where now?
    Woon, ECY
    Threadgill, MD
    CURRENT MEDICINAL CHEMISTRY, 2005, 12 (20) : 2373 - 2392