title: Polydatin Protecting Kidneys against Hemorrhagic Shock-Induced Mitochondrial Dysfunction via SIRT1 Activation and p53 Deacetylation.
abstract: OBJECTIVE
  To ascertain if mitochondrial dysfunction (MD) of kidney cells is present in severe hemorrhagic shock and to investigate whether polydatin (PD) can attenuate MD and its protective mechanisms.
  
  
  METHODS
  Renal tubular epithelial cells (RTECs) from rat kidneys experiencing HS and a cell line (HK-2) under hypoxia/reoxygenation (H/R) treatment were used. Morphology and function of mitochondria in isolated RTECs or cultured HK-2 cells were evaluated, accompanied by mitochondrial apoptosis pathway-related proteins.
  
  
  RESULTS
  Severe MD was found in rat kidneys, especially in RTECs, as evidenced by swollen mitochondria and poorly defined cristae, decreased mitochondrial membrane potential (ΔΨm), and reduced ATP content. PD treatment attenuated MD partially and inhibited expression of proapoptotic proteins. PD treatment increased SIRT1 activity and decreased acetylated-p53 levels. Beneficial effect of PD was abolished partially when the SIRT1 inhibitor Ex527 was added. Similar phenomena were shown in the H/R cell model; when pifithrin-α (p53 inhibitor) was added to the PD/Ex527 group, considerable therapeutic effects were regained compared with the PD group apart from increased SIRT1 activity.
  
  
  CONCLUSIONS
  MD is present in severe HS, and PD can attenuate MD of RTECs via the SIRT1-p53 pathway. PD might be a promising therapeutic drug for acute renal injury.
authors.affiliation: Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Guangdong Key Lab of Shock and Microcirculation Research, Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Zhongqing
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Guangdong Key Lab of Shock and Microcirculation Research, Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Siqi
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Guangdong Key Lab of Shock and Microcirculation Research, Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xingmin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Anesthesiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, China.
authors.forename: Youguang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Guangdong Key Lab of Shock and Microcirculation Research, Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Ke-seng
authors.initials: KS
authors.lastname: Zhao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002227:Carbazoles / Q000737:chemistry / Q000494:pharmacology; D015687:Cell Hypoxia; D002478:Cells, Cultured; D005260:Female; D005960:Glucosides / Q000494:pharmacology*; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000473:pathology*; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C550547:6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide; D002227:Carbazoles; D005960:Glucosides; D020011:Protective Agents; D013267:Stilbenes; D016159:Tumor Suppressor Protein p53; D056564:Sirtuin 1; D010100:Oxygen; C058229:polydatin