Affiliation:
1. The Fourth Affiliated Hospital of Harbin Medical University
Abstract
Abstract
Abstract
Background: The α/β-hydrolase domain 2 (ABHD2) genes which was expressed in the alveolar type II cells (AT-II cells) have been identified as down-regulated genes in human emphysematous lungs. Meanwhile, ABHD2 is considered a triacylglycerol lipase. We investigated how the ABHD2 gene is involved in the development of emphysema by affecting lipid metabolism.
Methods: We treated A549 cells (whose biological characteristics were similar to those of AT-II cells) with/without ABHD2 knockdown at 0,50,100umol/L palmitic acid (PA). The cells were stained by Oil Red O, probe DCFH-DA, Annexin V-FITC/PI. The contents of intracellular triglyceride, MDA, Caspase-3 activity and cell viability were determined. We analyzed of C57BL6 and Abhd2 knockdown mice at different ages. The triglyceride, cholesterol and MDA level in mouse serum were measured. The contents of triglyceride, Malondialdehyde (MDA), Caspase-3 activity in mouse lung tissues were determined. The lung tissues were stained with hematoxylin and eosin, Oil Red O and TUNEL.
Results: We found that there were excessive deposition of triglyceride, lipid peroxidation, decreased cell viability and increased apoptosis in the cells with ABHD2 knockdown, showing lipid toxicity. At the same time, ABHD2 knockdown aggravates the lipid toxicity induced by PA in the A549 cells. ABHD2 deficiency resulted in abnormal lipid metabolism and lipid peroxidation in serum of mice. Meanwhile, these mice developed spontaneous gradual progression of emphysema, due to abnormal lipid metabolism, lipid peroxidation and enhanced apoptosis in lung tissues of ABHD2 knockdown mice.
Conclusions: Our findings suggest that ABHD2 knockdown can induce emphysema by accelerating triglyceride deposition.
Keywords: ABHD2 knockdown, Emphysema, ATGL, Triglyceride Deposition, lipid toxicity
Publisher
Research Square Platform LLC
Reference30 articles.
1. The lipid profile parameter in chronic obstructive pulmonary disease patients and correlation with severity of disease [J];Jain B;J Cardio-Thoracic Med,2017
2. Lipid metabolism in chronic obstructive pulmonary disease [J];Chen H;Int J COPD,2019
3. Lipids in chronic obstructive pulmonary disease: a target for future therapy? [Z];Vlahos R;American Thoracic Society,2020
4. Lipid-based biomarkers for CVD, COPD, and aging – A translational perspective [J];Ekroos K;Prog Lipid Res,2020
5. Adipose Triglyceride Lipase Regulation: An Overview [J];Cerk IK;Curr Protein Pept Sci,2018