Role of COX2 in Cellular Senescence
Başlık:
Role of COX2 in Cellular Senescence
Yazar:
Feng, Mingxiao, author.
ISBN:
9780438113152
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (130 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Advisors: Minsub Shim Committee members: Hexin Chen; Hippokratis Kiaris; Maria Pena; Alan Waldman.
Özet:
The survivors of childhood cancers are often associated with the adverse late effects including hypoplasia, fatigue, and infertility, which are characteristics of aging. However, the underlying mechanisms of the late effects of chemotherapy are still elusive. We have found that transgenic cyclooxygenase-2 (COX2) expression causes premature aging phenotypes. Since COX2 expression is highly induced by various chemotherapeutic agents, we further investigated the possible link between COX2 and the late effects of chemotherapy. Treatment of juvenile wild-type mice with doxorubicin (DOX), an anthracycline-based chemotherapeutic agent, resulted in premature aging phenotypes and escalated cellular senescence level in various tissues. We found that tissue expression of COX2 persists even 11 weeks after cessation of DOX treatment. Moreover, COX inhibitors successfully alleviated cellular senescence level and early aging phenotypes in DOX-treated mice. In addition, genetic deletion or pharmacological inhibition of COX2 in cell lines significantly decreased DOX-induced cellular senescence. Also, treatment with COX inhibitors induced cell death among senescent cells, possibly through inhibition of p70 and Bcl signaling, consistent with our in vivo observation. Our results indicate that chemotherapy-induced COX2 may play an important role in the late effects of chemotherapy. COX inhibitors, which have been used in medical treatments for centuries, could serve as senolytic drugs by eliminating senescent cells to restore homeostasis and rescue aging phenotypes.
Notlar:
School code: 0202
Tüzel Kişi Ek Girişi:
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(689862.1) | 689862-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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