title: Inhibitory effects and mechanism of 25-OH-PPD on glomerular mesangial cell proliferation induced by high glucose.
abstract: OBJECTIVE
  To investigate the protective effects and potential mechanism of the compound 25-OH-PPD (PPD) on the glomerular mesangial cells (GMC) under high glucose condition.
  
  
  METHODS
  The hypertrophic GMC cells were established by DMEM containing glucose and randomly divided into five groups, including the normal control group (Control), the high glucose model group (HG, 25 mmolL(-1)), the PPD low dose group (1μmolL(-1), PPD-L), the PPD middle dose group (5μmolL(-1), PPD -M) and the PPD high dose group (10μmolL(-1), UCN-H). The GMC were incubated for 48h under different treatment factors. Total protein content was determined by Lowry method. The diameter of the single GMC and volume were measured by computer photograph analysis system. The GMC cell viability was analyzed by MTT assay. The level of malondialdehyde (MDA), the content of glutathione (GSH) and superoxide dismutase (SOD) activity were measured by ELISA. [Ca(2+)]і transient was measured by Till image system and by cell-loading Fura-2/AM. The expression of COX-1 and COX-2 were also determined using ELISA method.
  
  
  RESULTS
  The viability of GMC and the total protein content were decreased in HG group, different dosage PPD group could increase these indexes (P<0.05). The level of MDA was increased, the content of GSH and SOD was decreased in HG group, while PPD could reduce the MDA and enhance GSH and SOD (P<0.05). Following treatment with different dosage (PPD-L, PPD-M or PPD-H), the [Ca(2+)]і transient was reduced (P<0.05 or P<0.01). Moreover, the expression of COX-1 was decreased while COX-2 expression was increased in different dosage PPD groups.
  
  
  CONCLUSIONS
  The protective effects of PPD on GMC from HG-induced hypertrophy may be associated with the inhibition of [Ca(2+)]і transient and decreasing expression of COX-1 via the oxidative-stress injure pathway.
authors.affiliation: Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Junxian
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, Liaoning Medical University, JinZhou 121001, China.
authors.forename: Chunna
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: The First Affiliated Hospital of Liaoning Medical University, JinZhou 121001, China. Electronic address: springnanaliu@163.com.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology*; D005947:Glucose; D005979:Glutathione Peroxidase / Q000378:metabolism; D006984:Hypertrophy / Q000139:chemically induced / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: C529607:25-hydroxyprotopanaxadiol; D036145:Ginsenosides; D008565:Membrane Proteins; D020011:Protective Agents; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D013482:Superoxide Dismutase; D005947:Glucose; D002118:Calcium
keywords: 25-OH-PPD; COX-2; Calcium transient; Diabetic nephropathy; Glomerular mesangial cell; High glucose level; Oxidative stress