PMID- 30739301
OWN - NLM
STAT- MEDLINE
DCOM- 20190902
LR  - 20190902
IS  - 1572-8773 (Electronic)
IS  - 0966-0844 (Linking)
VI  - 32
IP  - 2
DP  - 2019 Apr
TI  - Profiling of nuclear copper-binding proteins under hypoxic condition.
PG  - 329-341
LID - 10.1007/s10534-019-00171-x [doi]
AB  - Under hypoxic condition, copper (Cu) accumulates in cell nuclei, and regulates 
      the activity of hypoxia-inducible factor-1 (HIF-1) through Cu-binding proteins 
      (CuBPs). To understand the CuBPs in the nucleus, proteomic approach was 
      undertaken to explore the dynamic changes of the CuBPs in response to hypoxia. 
      Human umbilical vein endothelial cells (HUVECs) were treated with 
      dimethyloxalylglycine in a final concentration of 100 muM for 4 h to induce 
      hypoxia, resulting in the accumulation of HIF-1alpha and Cu in the nucleus. Cu 
      immobilized metal affinity chromatography was applied to extract the CuBPs, 
      followed by identification using nanoliter-liquid chromatograpy combined with 
      quadrupole time of flight tandem mass spectrometry (nanoLC-Q-TOF-MS/MS). There 
      were 278 nuclear proteins that were found as CuBPs in the induced hypoxic group 
      in contrast to 218 CuBPs in the control group. Functional annotation of these 
      proteins in gene ontology category revealed that proteins participating in 
      negative regulation of transcription from RNA polymerase II promoter were 
      dramatically enriched by induced hypoixc treatment. Label-free quantitative 
      proteomic approach identified quantitative changes of nuclear proteome; of 17 
      differentially expressed proteins, 8 were downregulated and 9 were upregulated in 
      the induced hypoxic nuclei. Four of the 17 proteins were CuBPs, including ILF2 
      and TRA2B, both were downregulated, and LMNA and HSPB1, both were upregulated. We 
      confirmed the protein change of ALB, LMNA and HSPB1 (HSP27) in real hypoxia, and 
      suggested that the identified CuBPs could be the target for further study of Cu 
      regulation of HIF-1 activity in the nucleus.
FAU - Fu, Haiying
AU  - Fu H
AUID- ORCID: 0000-0002-4826-6903
AD  - Regenerative Medicine Research Center, Sichuan University West China Hospital, 
      Chengdu, 610041, Sichuan, China.
FAU - Ding, Xueqin
AU  - Ding X
AD  - Regenerative Medicine Research Center, Sichuan University West China Hospital, 
      Chengdu, 610041, Sichuan, China.
FAU - Zhang, Wenjing
AU  - Zhang W
AD  - Regenerative Medicine Research Center, Sichuan University West China Hospital, 
      Chengdu, 610041, Sichuan, China.
FAU - Kang, Y James
AU  - Kang YJ
AUID- ORCID: 0000-0001-8449-7904
AD  - Regenerative Medicine Research Center, Sichuan University West China Hospital, 
      Chengdu, 610041, Sichuan, China. jameskang@vip.163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190209
PL  - Netherlands
TA  - Biometals
JT  - Biometals : an international journal on the role of metal ions in biology, 
      biochemistry, and medicine
JID - 9208478
RN  - 0 (Carrier Proteins)
RN  - 0 (copper-binding protein)
SB  - IM
MH  - Algorithms
MH  - Carrier Proteins/*metabolism
MH  - Cell Nucleus/*metabolism
MH  - Cells, Cultured
MH  - Human Umbilical Vein Endothelial Cells/cytology/metabolism
MH  - Humans
MH  - Hypoxia/*metabolism
OTO - NOTNLM
OT  - Copper binding proteins
OT  - Cu
OT  - Hypoxia
OT  - Proteomics
EDAT- 2019/02/11 06:00
MHDA- 2019/09/03 06:00
CRDT- 2019/02/11 06:00
PHST- 2018/06/08 00:00 [received]
PHST- 2019/01/14 00:00 [accepted]
PHST- 2019/02/11 06:00 [pubmed]
PHST- 2019/09/03 06:00 [medline]
PHST- 2019/02/11 06:00 [entrez]
AID - 10.1007/s10534-019-00171-x [pii]
AID - 10.1007/s10534-019-00171-x [doi]
PST - ppublish
SO  - Biometals. 2019 Apr;32(2):329-341. doi: 10.1007/s10534-019-00171-x. Epub 2019 Feb 
      9.