Proteomic detection of changes in protein expression induced by cordycepin in human hepatocellular carcinoma BEL-7402 cells.
ABSTRACT The nucleoside analogue cordycepin (3 '-deoxyadenosine, 3 '-dA), one of the components of Cordyceps militaris, has been shown to inhibit the growth of various tumor cells. However, the probable mechanism is still obscure. In this study, the inhibition of cell growth and changes in protein expression induced by cordycepin were investigated in BEL-7402 cells. Using the MTT assay and flow cytometry, we found that cordycepin inhibits cell viability and induces apoptosis in BEL-7402 cells. Additionally, the proteins were separated using two-dimensional polyacrylamide gel electrophoresis, and eight proteins were found to be significantly affected by cordycepin compared to untreated control; among them, two were downregulated and six were upregulated. Of the eight proteins, six were identified with peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) after in-gel trypsin digestion. These proteins are involved in various aspects of cellular metabolism. It is suggested that the effect of cordycepin on the growth of tumor cells is significantly related to the metabolism-associated protein expression induced by cordycepin.
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ABSTRACT: The unfolded protein response (UPR) is involved in a diverse range of pathologies triggered by endoplasmic reticulum (ER) stress. Endeavor to seek selective regulators of the UPR is a promising challenge towards therapeutic intervention in ER stress-related disorders. In the present report, we describe aberrant, differential and bidirectional regulation of the UPR by 3'-deoxyadenosine (cordycepin) towards cell survival. 3'-Deoxyadenosine blocked ER stress-induced apoptosis via inhibiting the IRE1-JNK pro-apoptotic pathway. 3'-Deoxyadenosine also inhibited apoptosis through reinforcement of the pro-survival eIF2α signaling without affecting PERK activity. It was associated with depression of GADD34 that dephosphorylates eIF2α, and dephosphorylation of eIF2α by salubrinal mimicked the anti-apoptotic effect of 3'-deoxyadenosine. Unexpectedly, although 3'-deoxyadenosine caused activation of eIF2α, it inhibited downstream pro-apoptotic events including induction of ATF4 and expression of CHOP. Cooperation of adenosine transporter and A3 adenosine receptor, but not A1/A2 receptors, mediated the pluripotent effects of 3'-deoxyadenosine. In mice, ER stress caused activation of JNK, expression of CHOP and induction of apoptosis in renal tubules. The apoptosis was significantly attenuated by administration with 3'-deoxyadenosine, and it was correlated with blunted induction of JNK and CHOP in the kidney. These results disclosed atypical pro-survival regulation of the UPR by 3'-deoxyadenosine, which may be advantageous for the treatment of intractable, ER stress-related disorders.Cell death and differentiation 05/2011; 18(12):1876-88. · 8.24 Impact Factor
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ABSTRACT: Although hardly applied to human palaeoecology, bird fossils offer a unique opportunity for quantitative studies of the hominin habitat. Here we reconstruct the Homo habitat niche across a large area of the Palaearctic, based on a database of avian fauna for Pleistocene sites. Our results reveal a striking association between Homo and habitat mosaics. A mix of open savannah-type woodland, wetlands and rocky habitats emerges as the predominant combination occupied by Homo across a wide geographical area, from the earliest populations of the Lower Palaeolithic to the latest hunter-gatherer communities of the Upper Palaeolithic. This observation is in keeping with the view that such landscapes have had long standing selective value for hominins.Quaternary Science Reviews 01/2011; 30(11):1525-1532. · 4.08 Impact Factor
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ABSTRACT: Function exertion of specific proteins are key factors in disease progression, thus the systematical identification of those specific proteins is a prerequisite to understand various diseases. Though many proteins have been verified to impact on hepatitis, no systematical protein screening has been documented to hepatitis B virus (HBV) induced hepatitis, hindering the comprehensive understanding to this severe disease. To identify the major proteins in the progression of HBV infection from mild stage to severe stage. We performed an integrated strategy by combining two-dimensional electrophoresis (2-DE), peptide mass fingerprinting (PMF) analysis, and tissue microarray techniques to screen the functional proteins and detect the localization of those proteins. Interestingly, MS/MS identification revealed the expression level of alpha-1 antitrypsin (AAT) was significantly elevated in serum samples from patients with severe chronic hepatitis. Immunoblotting with a specific AAT antibody confirmed that AAT is highly expressed in serum samples from patients with hepatic carcinoma and severe chronic hepatitis. Furthermore, we observed that AAT is with highest expression in normal tissue and cells, but lowest in hepatic carcinoma and severe chronic hepatitis tissues and cells, suggesting the specific secretion of AAT from tissues and cells to serum. These results suggest the possibility of AAT as a potential biomarker for hepatitis B in diagnosis.Virology Journal 01/2011; 8:274. · 2.09 Impact Factor