PMID- 17540725
OWN - NLM
STAT- MEDLINE
DCOM- 20070926
LR  - 20070816
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 148
IP  - 9
DP  - 2007 Sep
TI  - Involvement of glyceraldehyde-3-phosphate dehydrogenase in tumor necrosis 
      factor-related apoptosis-inducing ligand-mediated death of thyroid cancer cells.
PG  - 4352-61
AB  - TNF-related apoptosis-inducing ligand (TRAIL) is cytotoxic to most thyroid cancer 
      cell lines, including those originating from anaplastic carcinomas, implying 
      TRAIL as a promising therapeutic agent against thyroid cancers. However, signal 
      transduction in TRAIL-mediated apoptosis is not clearly understood. In addition 
      to its well-known glycolytic functions, glyceraldehyde-3-phosphate dehydrogenase 
      (GAPDH) is a multifunctional protein, including its surprising role as a mediator 
      for cell death. In this study we explored the involvement of GAPDH in 
      TRAIL-mediated thyroid cancer cell death. In follicular undifferentiated thyroid 
      cells, S-nitrosylation and nuclear translocation of GAPDH appear to mediate 
      TRAIL-induced cell death at least partially, as evidenced by pretreatment with 
      N-nitro-L-arginine methyl ester, a competitive nitric oxide synthase inhibitor 
      that partially but significantly attenuated TRAIL-induced apoptosis through the 
      reduction of S-nitrosylation and nuclear translocation of GAPDH. In addition, 
      GAPDH small interfering RNA partially prevented the apoptotic effect of TRAIL, 
      although TRAIL-induced nitric oxide synthase stimulation and production of nitric 
      oxide were not attenuated. Furthermore, nuclear localization of GAPDH was 
      observed in another thyroid cancer cell line, KTC2, which is also sensitive to 
      TRAIL, but not in those TRAIL insensitive cell lines: ARO, KTC1, and KTC3. These 
      data indicate that nitric oxide-mediated S-nitrosylation of GAPDH and subsequent 
      nuclear translocation of GAPDH might function as a mediator of TRAIL-induced cell 
      death in thyroid cancer cells.
FAU - Du, Zhen-Xian
AU  - Du ZX
AD  - Department of Endocrinology and Metabolism, the 1st Affiliated Hospital, China 
      Medical University, Shenyang 110001, China. dzx_doctor@hotmail.com
FAU - Wang, Hua-Qin
AU  - Wang HQ
FAU - Zhang, Hai-Yan
AU  - Zhang HY
FAU - Gao, Da-Xin
AU  - Gao DX
LA  - eng
PT  - Journal Article
DEP - 20070531
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (RNA, Neoplasm)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - EC 1.2.1.9 (Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+))
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Apoptosis/*physiology
MH  - Caspase 3/metabolism
MH  - Cell Death
MH  - Cell Line, Tumor
MH  - Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+)/*genetics/metabolism
MH  - Humans
MH  - RNA, Neoplasm/genetics/isolation & purification
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - TNF-Related Apoptosis-Inducing Ligand/*physiology
MH  - Thyroid Neoplasms/*pathology
EDAT- 2007/06/02 09:00
MHDA- 2007/09/27 09:00
CRDT- 2007/06/02 09:00
PHST- 2007/06/02 09:00 [pubmed]
PHST- 2007/09/27 09:00 [medline]
PHST- 2007/06/02 09:00 [entrez]
AID - en.2006-1511 [pii]
AID - 10.1210/en.2006-1511 [doi]
PST - ppublish
SO  - Endocrinology. 2007 Sep;148(9):4352-61. doi: 10.1210/en.2006-1511. Epub 2007 May 
      31.