Yun Wang1, Yu-Han Gu1, Li-Ye Liang1, Ming Liu2, Bin Jiang3, Mei-Jia Zhu1, Xin Wang1, Lin Shi1. 1. Department of Clinical Pharmacology, School of Pharmacy, China Medical University, Shenyang, China. 2. Department of Drug Control, China Criminal Police University, Shenyang, China. 3. Department of Cardiovascular Ultrasound, The First Hospital, China Medical University, Shenyang, China.
Abstract
OBJECTIVES: Methamphetamine (MA) abuse evokes pulmonary toxicity. The aim of our study is to investigate if autophagy is induced by MA and if autophagy-initiated apoptosis in alveolar epithelial cells is involved in MA-induced chronic pulmonary toxicity. MATERIALS AND METHODS: The rats in Control group and MA group were tested by Doppler and HE staining. The alveolar epithelial cells were treated with MA, following by western blot, RT-PCR and immunofluorescence assay. RESULTS: Chronic exposure to MA resulted in lower growth ratio of weight and in higher heart rate and peak blood flow velocity of the main pulmonary artery of rats. MA induced infiltration of inflammatory cells in lungs, more compact lung parenchyma, thickened alveolar septum and reduction in the number of alveolar sacs. In alveolar epithelial cells, the autophagy marker LC3 and per cent of cells containing LC3-positive autophagosome were significantly increased. MA dose dependently suppressed the phosphorylation of mTOR to inactivate mTOR, elicited autophagy regulatory proteins LC3 and Beclin-1, accelerated the transformation from LC3 I to LC3 II and initiated apoptosis by decreasing Bcl-2 and increasing Bax, Bax/Bcl-2 and cleaved Caspase 3. The above results suggest that sustained autophagy was induced by long-term exposure to MA and that the increased Beclin-1 autophagy initiated apoptosis in alveolar epithelial cells. CONCLUSIONS: Concurrence of autophagy with apoptosis in alveolar epithelial cells contributes to chronic pulmonary toxicity induced by MA.
OBJECTIVES:Methamphetamine (MA) abuse evokes pulmonary toxicity. The aim of our study is to investigate if autophagy is induced by MA and if autophagy-initiated apoptosis in alveolar epithelial cells is involved in MA-induced chronic pulmonary toxicity. MATERIALS AND METHODS: The rats in Control group and MA group were tested by Doppler and HE staining. The alveolar epithelial cells were treated with MA, following by western blot, RT-PCR and immunofluorescence assay. RESULTS: Chronic exposure to MA resulted in lower growth ratio of weight and in higher heart rate and peak blood flow velocity of the main pulmonary artery of rats. MA induced infiltration of inflammatory cells in lungs, more compact lung parenchyma, thickened alveolar septum and reduction in the number of alveolar sacs. In alveolar epithelial cells, the autophagy marker LC3 and per cent of cells containing LC3-positive autophagosome were significantly increased. MA dose dependently suppressed the phosphorylation of mTOR to inactivate mTOR, elicited autophagy regulatory proteins LC3 and Beclin-1, accelerated the transformation from LC3 I to LC3 II and initiated apoptosis by decreasing Bcl-2 and increasing Bax, Bax/Bcl-2 and cleaved Caspase 3. The above results suggest that sustained autophagy was induced by long-term exposure to MA and that the increased Beclin-1 autophagy initiated apoptosis in alveolar epithelial cells. CONCLUSIONS: Concurrence of autophagy with apoptosis in alveolar epithelial cells contributes to chronic pulmonary toxicity induced by MA.
Authors: Adriana C Hernandez-Santini; Anum N Mitha; Daniela Chow; Mohamed F Hamed; Azad L Gucwa; Valerie Vaval; Luis R Martinez Journal: Sci Rep Date: 2021-04-15 Impact factor: 4.379