Betulinic acid-mediated inhibitory effect on hepatitis B virus by suppression of manganese superoxide dismutase expression
Φόρτωση...
Ημερομηνία
Συγγραφείς
Yao, D. C.
Li, H. W.
Gou, Y. L.
Zhang, H. M.
Vlessidis, A. G.
Zhou, H. Y.
Evmiridis, N. P.
Liu, Z. X.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Wiley-Blackwell
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Febs Journal
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
The betulinic acid (BetA) purified from Pulsatilla chinensis (PC) has been found to have selective inhibitory effects on hepatitis B virus (HBV). In hepatocytes from HBV-transgenic mice, we showed that BetA substantially inhibited HBV replication by downregulation of manganese superoxide dismutase (SOD2) expression, with subsequent reactive oxygen species generation and mitochondrial dysfunction. Also, the HBV X protein (HBx) is suppressed and translocated into the mitochondria followed by cytochrome c release. Further investigation revealed that SOD2 expression was suppressed by BetA-induced cAMP-response element-binding protein dephosphorylation at Ser133, which subsequently prevented SOD2 transcription through the cAMP-response element-binding protein-binding motif on the SOD2 promoter. SOD2 overexpression abolished the inhibitory effect of BetA on HBV replication, whereas SOD2 knockdown mimicked this effect, indicating that BetA-mediated HBV clearance was due to modulation of the mitochondrial redox balance. This observation was further confirmed in HBV-transgenic mice, where both BetA and PC crude extracts suppressed SOD2 expression, with enhanced reactive oxygen species generation in liver tissues followed by substantial HBV clearance. We conclude that BetA from PC could be a good candidate for anti-HBV drug development.
Περιγραφή
Λέξεις-κλειδιά
apoptosis, creb, mitochondrial, pulsatilla chinensis, reactive oxygen species, element-binding protein, nf-kappa-b, x-protein, transgenic mice, somatostatin gene, oxidative stress, redox regulation, protective role, cell-survival, human liver
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
<Go to ISI>://000264882700016
http://onlinelibrary.wiley.com/store/10.1111/j.1742-4658.2009.06988.x/asset/j.1742-4658.2009.06988.x.pdf?v=1&t=hmst47rc&s=fb2e0b7d3aa696b4f22d11a0705ae9bbe62d59df
http://onlinelibrary.wiley.com/store/10.1111/j.1742-4658.2009.06988.x/asset/j.1742-4658.2009.06988.x.pdf?v=1&t=hmst47rc&s=fb2e0b7d3aa696b4f22d11a0705ae9bbe62d59df
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείας