Next Article in Journal
Cinnamomum cassia Essential Oil Inhibits α-MSH-Induced Melanin Production and Oxidative Stress in Murine B16 Melanoma Cells
Next Article in Special Issue
A Novel Thylakoid Ascorbate Peroxidase from Jatrophacurcas Enhances Salt Tolerance in Transgenic Tobacco
Previous Article in Journal
Formation of Apatite Coatings on an Artificial Ligament Using a Plasma- and Precursor-Assisted Biomimetic Process
Previous Article in Special Issue
Insulin-Dependent H2O2 Production Is Higher in Muscle Fibers of Mice Fed with a High-Fat Diet
Int. J. Mol. Sci. 2013, 14(9), 19169-19185; doi:10.3390/ijms140919169

Involvement of Calcium-Mediated Reactive Oxygen Species in Inductive GRP78 Expression by Geldanamycin in 9L Rat Brain Tumor Cells

1,* , 2
1 Department of Bioresources, Da-Yeh University, Changhua 515, Taiwan 2 Department of Life Science and Institute of Biotechnology, National Tsing Hua University, Hsinchu 300, Taiwan 3 School of Chinese Pharmaceutical Science and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan 4 Department of Medical Research, Tungs' Taichung MetroHarbor Hospital, Taichung 435, Taiwan
* Author to whom correspondence should be addressed.
Received: 24 July 2013 / Revised: 19 August 2013 / Accepted: 9 September 2013 / Published: 18 September 2013
(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)
View Full-Text   |   Download PDF [1421 KB, uploaded 19 June 2014]   |   Browse Figures


Treatment with geldanamycin (GA) leads to an increase in [Ca2+]c and the production of reactive oxygen species (ROS) in rat brain tumor 9L RBT cells. GA-exerted calcium signaling was blocked by BAPTA/AM and EGTA. The effect of GA on [Ca2+]c was significantly reduced in the presence of thapsigargin (TG) and ruthenium red (RR). GA-induced GRP78 expression is significantly decreased in the presence of BAPTA/AM, EGTA and RR, suggesting that the calcium influx from the extracellular space and intracellular calcium store oscillations are contributed to by the calcium mobilization and GRP78 expression induced by GA. The induced GRP78 expression is sensitive to added U73122 and Ro-31-8425, pinpointing the involvement of phospholipase C (PLC) and protein kinase C (PKC) in GA-induced endoplasmic reticulum (ER) stress. The antioxidants N-acetylcysteine (NAC), BAPTA/AM, EGTA and H7 also have significant inhibitory effects on ROS generation. Finally, neither H7 nor NAC was able to affect the calcium response elicited by GA. Our results suggest that the causal signaling cascade during GA-inducted GRP78 expression occurs via a pathway that connects PLC to cytoplasmic calcium increase, PKC activation and, then, finally, ROS generation. Our data provides new insights into the influence of GA on ER stress response in 9L RBT cells.
Keywords: geldanamycin; calcium; PKC; ROS; GRP78 geldanamycin; calcium; PKC; ROS; GRP78
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
EndNote |
MDPI and ACS Style

Sun, F.-C.; Shyu, H.-Y.; Lee, M.-S.; Lee, M.-S.; Lai, Y.-K. Involvement of Calcium-Mediated Reactive Oxygen Species in Inductive GRP78 Expression by Geldanamycin in 9L Rat Brain Tumor Cells. Int. J. Mol. Sci. 2013, 14, 19169-19185.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here


[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert