Nicotine-induced autophagy via AMPK/mTOR pathway exerts protective effect in colitis mouse model.

Abstract

Epidemiological studies have shown that cigarette smoking is beneficial in ulcerative colitis and that nicotine may be responsible for this effect. However, the mechanism remains unclear. In a previous study, nicotine was found to induce autophagy in intestinal cells. Here, we evaluated the effect of nicotine-induced autophagy in a dextran sodium sulfate (DSS)-induced colitis mouse model. C57BL/6 adult male mice drank DSS water solution freely for seven consecutive days, and then tap water was administered. The effect of nicotine treatment was examined in the DSS model, including colon length, disease severity, histology of the colon tissue, and inflammation levels. Moreover, autophagy levels were detected by Western blot analysis (LC3II/LC3I, p62, and beclin-1). The levels of DSS-induced colitis were significantly decreased following nicotine treatment. The disease activity score, body weight, histologic damage scores, and the level of colonic inflammatory factors of nicotine-treated mice all decreased compared to those of the control mice. Additionally, nicotine enhanced the expression of LC3II/LC3I and beclin-1 but decreased the p62 protein level. Inhibiting autophagy by 3-MA attenuated the protective effects of nicotine on colitis. Additionally, both in vitro and in vivo experiments showed changes in AMPK-mTOR-P70S6K during this process. These results suggest that nicotine improved colitis by regulating autophagy and provided a protective effect against DSS-induced colitis.

• Authors: Qian Gao, Pinduan Bi, Ding Luo, Ying Guan, Wanli Zeng, Haiying Xiang, Qili Mi, Guangyu Yang, Xuemei Li, Bin Yang
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 317 Pg. 108943 (Feb 01 2020) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 31926917 (Publication Type: Journal Article)
• Copyright: Copyright © 2020. Published by Elsevier B.V.

Chemical References

• 3-methyladenine
• Nicotine
• Dextran Sulfate
• mTOR protein, mouse
• Ribosomal Protein S6 Kinases, 70-kDa
• TOR Serine-Threonine Kinases
• Adenylate Kinase
• Adenine

Topics

• Adenine (analogs & derivatives, pharmacology)
• Adenylate Kinase (genetics, metabolism)
• Animals
• Autophagy (drug effects)
• Colitis (chemically induced, prevention & control)
• Dextran Sulfate (toxicity)
• Gene Expression Regulation (drug effects)
• Mice
• Mice, Inbred C57BL
• Nicotine (pharmacology)
• Ribosomal Protein S6 Kinases, 70-kDa (genetics, metabolism)
• TOR Serine-Threonine Kinases (genetics, metabolism)