TY  - JOUR
A1  - Luger, Anna-Luisa
A1  - Sauer, Benedikt
A1  - Lorenz, Nadja Irene
A1  - Engel, Anna Larissa
A1  - Braun, Yannick
A1  - Voß, Martin
A1  - Harter, Patrick Nikolaus
A1  - Steinbach, Joachim Peter
A1  - Ronellenfitsch, Michael Wilfried
T1  - Doxycycline impairs mitochondrial dunction and protects human glioma cells from hypoxia-induced cell death : implications of using tet-inducible systems
T2  - International journal of molecular sciences
N2  - Inducible gene expression is an important tool in molecular biology research to study protein function. Most frequently, the antibiotic doxycycline is used for regulation of so-called tetracycline (Tet)-inducible systems. In contrast to stable gene overexpression, these systems allow investigation of acute and reversible effects of cellular protein induction. Recent reports have already called for caution when using Tet-inducible systems as the employed antibiotics can disturb mitochondrial function and alter cellular metabolism by interfering with mitochondrial translation. Reprogramming of energy metabolism has lately been recognized as an important emerging hallmark of cancer and is a central focus of cancer research. Therefore, the scope of this study was to systematically analyze dose-dependent metabolic effects of doxycycline on a panel of glioma cell lines with concomitant monitoring of gene expression from Tet-inducible systems. We report that doxycycline doses commonly used with inducible expression systems (0.01–1 µg/mL) substantially alter cellular metabolism: Mitochondrial protein synthesis was inhibited accompanied by reduced oxygen and increased glucose consumption. Furthermore, doxycycline protected human glioma cells from hypoxia-induced cell death. An impairment of cell growth was only detectable with higher doxycycline doses (10 µg/mL). Our findings describe settings where doxycycline exerts effects on eukaryotic cellular metabolism, limiting the employment of Tet-inducible systems.
KW  - doxycycline
KW  - tetracycline
KW  - inducible gene expression
KW  - Tet-inducible system
KW  - hypoxia-induced cell death
KW  - mitochondria
KW  - tumor metabolism
KW  - glioblastoma
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/46612
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-466128
SN  - 1422-0067
SN  - 1661-6596
N1  - This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
VL  - 19
IS  - 5, Art. 1504
SP  - 1
EP  - 17
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -