A proteomic view of Caenorhabditis elegans caused by short-term hypoxic stress.
BACKGROUND
The nematode Caenorhabditis elegans is both sensitive and tolerant to hypoxic stress, particularly when the evolutionarily conserved hypoxia response pathway HIF-1/EGL-9/VHL is involved. Hypoxia-induced changes in the expression of a number of genes have been analyzed using whole genome microarrays in C. elegans, but the changes at the protein level in response to hypoxic stress still remain unclear.


RESULTS
Here, we utilized a quantitative proteomic approach to evaluate changes in the expression patterns of proteins during the early response to hypoxia in C. elegans. Two-dimensional difference gel electrophoresis (2D-DIGE) was used to compare the proteomic maps of wild type C. elegans strain N2 under a 4-h hypoxia treatment (0.2% oxygen) and under normoxia (control). A subsequent analysis by MALDI-TOF-TOF-MS revealed nineteen protein spots that were differentially expressed. Nine of the protein spots were significantly upregulated, and ten were downregulated upon hypoxic stress. Three of the upregulated proteins were involved in cytoskeletal function (LEV-11, MLC-1, ACT-4), while another three upregulated (ATP-2, ATP-5, VHA-8) were ATP synthases functionally related to energy metabolism. Four ribosomal proteins (RPL-7, RPL-8, RPL-21, RPS-8) were downregulated, indicating a decrease in the level of protein translation upon hypoxic stress. The overexpression of tropomyosin (LEV-11) was further validated by Western blot. In addition, the mutant strain of lev-11(x12) also showed a hypoxia-sensitive phenotype in subsequent analyses, confirming the proteomic findings.


CONCLUSIONS
Taken together, our data suggest that altered protein expression, structural protein remodeling, and the reduction of translation might play important roles in the early response to oxygen deprivation in C. elegans, and this information will help broaden our knowledge on the mechanism of hypoxia response.
Li
Hualing
H
Life Science College of Nanjing Agriculture University, Nanjing 210095, China.|Beijing Institute of Radiation Medicine, State Key Laboratory of Proteomics, Beijing 100850, China.|Medical College of Yangzhou University, Yangzhou 225001, China.
Ren
Changhong
C
Beijing Institute of Radiation Medicine, State Key Laboratory of Proteomics, Beijing 100850, China.
Shi
Jinping
J
Beijing Institute of Radiation Medicine, State Key Laboratory of Proteomics, Beijing 100850, China.
Hang
Xingyi
X
Beijing Institute of Radiation Medicine, State Key Laboratory of Proteomics, Beijing 100850, China.
Zhang
Feilong
F
Beijing Institute of Radiation Medicine, State Key Laboratory of Proteomics, Beijing 100850, China.
Gao
Yan
Y
Beijing Institute of Radiation Medicine, State Key Laboratory of Proteomics, Beijing 100850, China.
Wu
Yonghong
Y
Beijing Institute of Radiation Medicine, State Key Laboratory of Proteomics, Beijing 100850, China.
Xu
Langlai
L
Life Science College of Nanjing Agriculture University, Nanjing 210095, China.
Chen
Changsheng
C
Department of Health Statistics, School of Military Preventive Medicine, Fourth Military Medical University, Xi'an 710032, China.
Zhang
Chenggang
C
Beijing Institute of Radiation Medicine, State Key Laboratory of Proteomics, Beijing 100850, China.