Silica nanoparticles induces cell death in lung epithelial cells through mitochondria and endoplasmic reticulum pathways

Silica nanoparticles induces cell death in lung epithelial cells through

mitochondria and endoplasmic reticulum pathways.

Tien-Hui Lu

, Ling-Mei Tsai

, Dong-Zong Hung

, Cheng-Chieh Yen

, Chin-Chuan Su

, Yi-Chang Su

, Chun-Fa Huang

, Shing-Hwa Liu

, Ya-Wen Chen

1

Graduate Institute of Basic Medical Science,

Department of Physiology, China Medical University, Taichung, Taiwan

2

Toxicology Center, China Medical University Hospital, Taichung, Taiwan

3

Department of Occupational Safety and Health, Chung Shan Medical University, Taichung, Taiwan

4

Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan

5

School of Chinese Medicine, China Medical University, Taichung, Taiwan

6

Toxicology Center, China Medical University Hospital, Taichung, Taiwan

Abstract:

Silica nanoparticles (SiO

-NPs) are widely used in nanotechnology industry and

applications in various products. Previous studies have indicated that nanoparticles

can induce oxidative stress damage causing cell death. Alveolar type II epithelial cells

are known to be vulnerable to oxidative stress. However, the toxic effect of SiO

-NPs

on alveolar type II epithelial cell damage remains unclear. In this study, we investigate

the effect and possible mechanisms of SiO

-NPs on rat type II epithelial cell line (L2)

for 24–48 h. The results showed a decreased in cell viability and an increased in

annexin-V binding in a time- and dose-dependent manner. Meanwhile, after SiO

-NPs

exposure, the amount of silicon uptake and ROS production was correlated with the

concentration of SiO

-NPs at 24h, and the malondialdehyde (MDA) level increased in

a dose-dependent manner at 48h. SiO

-NPs also caused mitochondrial-dependent

apoptotic signals, including the increasing of caspase-3 activity, disruption of the

mitochondrial membrane potential, up-regulation of Bax and down-regulaton of Bcl-2

protein expression, activations of caspase cascades  and cleave poly(ADP-Ribose)

polymerase (PARP). Moreover, treatment of L2 cells with SiO

-NPs resulted in

endoplasmic reticulum (ER) stress, such as activating the protein expression of C/EBP

homologous protein (CHOP), X-box binding protein 1(XBP-1), caspase-12, and

decreasing the glucose-regulated protein 78/94 (GRP-78/-94) protein expression.

These results suggest that SiO

-NPs trigger an oxidative stress, and induce alveolar

epithelial cells apoptosis through mitochondria and endoplasmic reticulum pathways.

Keyword: Silica nanoparticle; Lung epithelial cells; Apoptosis; ROS; Mitochondria;

ER-stress