title: Nitric oxide inhibits autophagy via suppression of  JNK in meniscal cells.
abstract: OBJECTIVE
  Autophagy is a potential protective mechanism that is involved in several degenerative diseases. Nitric oxide (NO) is associated with programmed cellular death in meniscal cells, but whether it can induce autophagy is still undetermined. This study aims to investigate the interaction between autophagy and NO in normal human meniscal cells.
  
  
  METHODS
  Normal meniscal cells were harvested from female patients. NO donors and NO synthase inhibitors were used to regulate the level of NO. Changes in the incidence of autophagy and apoptosis were examined using flow cytometry, western blot and immunofluorescence methods. The effects of NO-mediated autophagy regulation of the expression of MMPs and aggrecanases (ADAMTS-4 and -5) were analysed by real-time PCR.
  
  
  RESULTS
  NO donors inhibited autophagy as well as augmented apoptosis in human meniscal cells with serum deprivation. Conversely, treatment with NOS inhibitors resulted in up-regulation of the autophagy level while repressing apoptosis. NOS inhibitor treatment also resulted in down-regulation of MMPs and aggrecanase mRNA expression. This effect of NOS inhibitor was also blocked by autophagy inhibitors. Our results also showed that NOS inhibitor enhanced Jun-N-terminal kinase (JNK) activation. Furthermore, SP600125, a selective JNK inhibitor, blocked up-regulation of autophagy by NOS inhibitor.
  
  
  CONCLUSIONS
  Our results demonstrated that NO augmented serum deprivation-induced apoptosis of meniscal cells via inhibition of autophagy through inactivation of JNK. Up-regulation of autophagy may be a potential approach in the treatment of meniscal tissue degeneration.
authors: Chao
authors: C
authors: Shen
authors: Jun
authors: J
authors: Yan
authors: Omer Faruk
authors: OF
authors: Erkocak
authors: Xin-Feng
authors: XF
authors: Zheng
authors: Xiao-Dong
authors: XD
authors: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors* / Q000502:physiology; D008592:Menisci, Tibial / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000235:genetics; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D048670:MAP Kinase Kinase 4