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Am J Chin Med. 2017;45(6):1273-1291. doi: 10.1142/S0192415X17500707.

Lutein Induces Autophagy via Beclin-1 Upregulation in IEC-6 Rat Intestinal Epithelial Cells.

Chang CJ1,2,3,4, Lin JF5, Hsiao CY6, Chang HH3,4,7, Li HJ3,4, Chang HH8, Lee GA3, Hung CF2,4,9.

Author information

1
* Division of Pediatric Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
2
‡ School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
3
§ Department of Chemistry, Fu-Jen Catholic University, New Taipei City, Taiwan.
4
¶ Graduate Institute of Biomedical and Pharmaceutical Science, Fu-Jen Catholic University, New Taipei City, Taiwan.
5
† Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
6
∥ Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan.
7
** Department of Cardiology, Tainan Municipal Hospital, Tainan, Taiwan.
8
†† Children's Hospital Informatics Program, Harvard-Massachusetts, Institute of Technology/Division of Health Sciences and Technology, Harvard Medical School, Boston, Massachusetts, USA.
9
‡‡ Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung, Taiwan.

Abstract

Lutein is a carotenoid with anti-oxidant properties. Autophagy, an evolutionarily conserved catabolic cellular pathway for coping with stress conditions, is responsive to reactive oxygen species (ROS) and degrades damaged organelles. We previously demonstrated that lutein can induce anti-oxidant enzymes to relieve methotrexate-induced ROS stress. We therefore hypothesized that lutein, which activates ROS-scavenging enzymes, can also induce autophagy for cell survival. In this study, we demonstrated that lutein treatment attenuated the reduction in cell viability caused by H2O2. Lutein dose-dependently induced the processing of microtubule-associated protein light chain 3 (LC3)-II, an autophagy marker protein, and accumulation of LC3-positive puncta in rat intestinal IEC-6 cells. Furthermore, (a) direct observation of autophagosome formation through transmission electron microscopy, (b) upregulation of autophagy-related genes including ATG4A, ATG5, ATG7, ATG12, and beclin-1 (BENC1), and (c) increased BECN1/Bcl-2 ratio confirmed the induction of autophagy by lutein. The results revealed that bafilomycin-A1-induced inhibition of autophagy reduced cell viability and increased apoptosis in lutein-treated cells, indicating a protective role of lutein-induced autophagy. Lutein treatment also activated adenosine monophosphate-activated protein kinase (AMPK), c-Jun N-terminal kinase (JNK), and p-38, but had no effects on the induction of extracellular signal-related kinase or inhibition of mTOR; however, the inhibition of activated AMPK, JNK, or p-38 did not attenuate lutein-induced autophagy. Finally, increased BECN1 expression levels were detected in lutein-treated cells, and BECN1 knockdown abolished autophagy induction. These results suggest that lutein-induced autophagy was mediated by the upregulation of BECN1 in IEC-6 cells. We are the first to demonstrate that lutein induces autophagy. Elevated autophagy in lutein-treated IEC-6 cells may have a protective role against various stresses, and this warrants further investigation.

KEYWORDS:

Apoptosis; Autophagy; Beclin-1; Intestinal Epithelial Cells; Lutein

PMID:
28893091
DOI:
10.1142/S0192415X17500707
[Indexed for MEDLINE]

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