Browsing by Author "Karademir, Betul"

Now showing 1 - 3 of 3

Citation Count: 0
Peripheral neuropathy as the side effect of proteasome inhibitors bortezomib and carfilzomib
(Elsevier Science inc, 2016) Sari-Kaplan, Gulce; Musunuri, Sravani; Wicher, Grzegorz; Jung, Tobias; Mi, Jia; Hacioglu-Bay, Husniye; Karademir, Betul
[No Abstract Available]
Citation Count: 3
Proteasome Inhibitors in Cancer Therapy and their Relation to Redox Regulation
(Bentham Science Publ Ltd, 2018) Sari, Gulce; Okat, Zehra; Sahin, Ali; Karademir, Betul
Redox homeostasis is important for the maintenance of cell survival. Under physiological conditions, redox system works in a balance and involves activation of many signaling molecules. Regulation of redox balance via signaling molecules is achieved by different pathways and proteasomal system is a key pathway in this process. Importance of proteasomal system on signaling pathways has been investigated for many years. In this direction, many proteasome targeting molecules have been developed. Some of them are already in the clinic for cancer treatment and some are still under investigation to highlight underlying mechanisms. Although there are many studies done, molecular mechanisms of proteasome inhibitors and related signaling pathways need more detailed explanations. This review aims to discuss redox status and proteasomal system related signaling pathways. In addition, cancer therapies targeting proteasomal system and their effects on redox-related pathways have been summarized.
Citation Count: 25
Proteomic approach for understanding milder neurotoxicity of Carfilzomib against Bortezomib
(Nature Portfolio, 2018) Karademir, Betul; Sari, Gulce; Jannuzzi, Ayse Tarbin; Musunuri, Sravani; Wicher, Grzegorz; Grune, Tilman; Jung, Tobias
The proteasomal system is responsible for the turnover of damaged proteins. Because of its important functions in oncogenesis, inhibiting the proteasomal system is a promising therapeutic approach for cancer treatment. Bortezomib (BTZ) is the first proteasome inhibitor approved by FDA for clinical applications. However neuropathic side effects are dose limiting for BTZ as many other chemotherapeutic agents. Therefore second-generation proteasome inhibitors have been developed including carfilzomib (CFZ). Aim of the present work was investigating the mechanisms of peripheral neuropathy triggered by the proteasome inhibitor BTZ and comparing the pathways affected by BTZ and CFZ, respectively. Neural stem cells, isolated from the cortex of E14 mouse embryos, were treated with BTZ and CFZ and mass spectrometry was used to compare the global protein pool of treated cells. BTZ was shown to cause more severe cytoskeletal damage, which is crucial in neural cell integrity. Excessive protein carbonylation and actin filament destabilization were also detected following BTZ treatment that was lower following CFZ treatment. Our data on cytoskeletal proteins, chaperone system, and protein oxidation may explain the milder neurotoxic effects of CFZ in clinical applications.