이수진
2018-03-23T04:33:12Z
2018-03-23T04:33:12Z
2013-09
Toxicology Letters, 23 October 2013, 223(1), p.25-34
0378-4274
https://www.sciencedirect.com/science/article/pii/S0378427413012873?via%3Dihub
http://hdl.handle.net/20.500.11754/51176
Oxidative stress created by environmental toxicants activates several signaling pathways. Autophagy is one of the first lines of defense against oxidative stress damage. The autophagy pathway can be induced and up-regulated in response to intracellular reactive oxygen species (ROS). Recently, we reported that fipronil (FPN)-induced mitochondria-dependent apoptosis is mediated through ROS in human neuroblastoma SH-SY5Y cells. In this study, we explored the role of autophagy to prevent FPN neurotoxicity. We investigated the modulation of FPN-induced apoptosis according to autophagy regulation. FPN activated caspase-9 and caspase-3, and induced nuclear fragmentation and condensation, all of which indicate that FPN-induced cell death was due to apoptosis. In addition, we observed FPN-induced autophagic cell death by monitoring the expression of LC3-II and Beclin-1. Exposure to FPN in SH-SY5Y cells led to the production of ROS. Treatment with N-acetyl-cysteine (NAC) effectively blocked both apoptosis and autophagy. Interestingly, pretreatment with rapamycin, an autophagy inducer, significantly enhanced the viability of FPN-exposed cells; the enhancement of cell viability was partially due to alleviation of FPN-induced apoptosis via a decrease in levels of cleaved caspase-3. However, pretreatment with 3-methyladenine (3MA) a specific inhibitor for autophagy, remarkably strengthened FPN toxicity and further induced activation of caspase-3 in these cells. Our studies suggest that FPN-induced cytotoxicity is modified by autophagy regulation and that rapamycin is neuroprotective against FPN-induced apoptosis through enhancing autophagy.
This work was supported by a grant from the Agenda Program (PJ008582), Rural Development Administration, Republic of Korea.
en
Elsevier Science B.V., Amsterdam.
Fipronil
Autophagy
Apoptosis
Neuroprotection
Rapamycin
Reactive oxygen species
Potential autophagy enhancers protect against fipronil-induced apoptosis in SH-SY5Y cells
Article
1
223
10.1016/j.toxlet.2013.08.015
25-34
TOXICOLOGY LETTERS
Park, Jae-Hyeon
Lee, Jeong-Eun
Park, Soo-Jin
Park, Kyung-Hun
Jeong, Mi-hye
Koh, Hyun-Chul
Lee, Soo-Jin
2013012205
S
COLLEGE OF MEDICINE[S]
DEPARTMENT OF MEDICINE
sjlee