期刊论文详细信息
Clinical Proteomics
Protein expression profiling of nuclear membrane protein reveals potential biomarker of human hepatocellular carcinoma
Nikhat Ahmed1  Saadia Zahid1  Abid Azhar3  M Ataur Rahman3  Atta M Nawabi2  A-Bashar Abdul Karim2  Jameson Forster2  Rizma Khan1  Yu-Jui Yvonne Wan2 
[1] Neurochemistry Research Unit Laboratory, Department of Biochemistry, University of Karachi, Karachi, PakistanNeurochemistry Research Unit Laboratory, Department of Biochemistry, University of Karachi, Karachi, PakistanNeurochemistry Research Unit Laboratory, Department of Biochemistry, University of Karachi, Karachi, Pakistan;The University of Kansas Medical Center, Kansas City Lawrence, Kansas, USAThe University of Kansas Medical Center, Kansas City Lawrence, Kansas, USAThe University of Kansas Medical Center, Kansas City Lawrence, Kansas, USA;The Karachi Institute of Biotechnology and Genetic Engineering, (KIBGE), University of Karachi, Karachi, PakistanThe Karachi Institute of Biotechnology and Genetic Engineering, (KIBGE), University of Karachi, Karachi, PakistanThe Karachi Institute of Biotechnology and Genetic Engineering, (KIBGE), University of Karachi, Karachi, Pakistan
关键词: Hepatocellular carcinoma;    Cytochrome b5A;    Two dimensional gel electrophoresis;    S-nitrosylation;    Proteomics;    ESI-Q-TOF MS/MS mass spectrometry;   
DOI  :  10.1186/1559-0275-10-6
来源: Humana Press Inc
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【 摘 要 】

Abstract

Background

Complex molecular events lead to development and progression of liver cirrhosis to HCC. Differentially expressed nuclear membrane associated proteins are responsible for the functional and structural alteration during the progression from cirrhosis to carcinoma. Although alterations/ post translational modifications in protein expression have been extensively quantified, complementary analysis of nuclear membrane proteome changes have been limited. Deciphering the molecular mechanism that differentiate between normal and disease state may lead to identification of biomarkers for carcinoma.

Results

Many proteins displayed differential expression when nuclear membrane proteome of hepatocellular carcinoma (HCC), fibrotic liver, and HepG2 cell line were assessed using 2-DE and ESI-Q-TOF MS/MS. From the down regulated set in HCC, we have identified for the first time a 15 KDa cytochrome b5A (CYB5A), ATP synthase subunit delta (ATPD) and Hemoglobin subunit beta (HBB) with 11, 5 and 22 peptide matches respectively. Furthermore, nitrosylation studies with S-nitrosocysteine followed by immunoblotting with anti SNO-cysteine demonstrated a novel and biologically relevant post translational modification of thiols of CYB5A in HCC specimens only. Immunofluorescence images demonstrated increased protein S-nitrosylation signals in the tumor cells and fibrotic region of HCC tissues. The two other nuclear membrane proteins which were only found to be nitrosylated in case of HCC were up regulated ATP synthase subunit beta (ATPB) and down regulated HBB. The decrease in expression of CYB5A in HCC suggests their possible role in disease progression. Further insight of the functional association of the identified proteins was obtained through KEGG/ REACTOME pathway analysis databases. String 8.3 interaction network shows strong interactions with proteins at high confidence score, which is helpful in characterization of functional abnormalities that may be a causative factor of liver pathology.

Conclusion

These findings may have broader implications for understanding the mechanism of development of carcinoma. However, large scale studies will be required for further verification of their critical role in development and progression of HCC.

【 授权许可】

Unknown   

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