» Articles » PMID: 33260152

Cigarette Smoke Extract Induces Airway Epithelial Cell Death Via Repressing PRMT6/AKT Signaling

Overview
Specialty Geriatrics
Date 2020 Dec 1
PMID 33260152
Citations 12
Authors
Affiliations
Soon will be listed here.
Abstract

Chronic obstructive pulmonary disease (COPD) is a severe public health threat world-wide. Cigarette smoke (CS)-induced airway epithelial cell death is a major pathway of pathogenesis in emphysema, a subtype of COPD. Protein arginine methyltransferase 6 (PRMT6) is a type I PRMT that catalyzes mono- and di-methylation on arginine residues within histone and non-histone proteins to modulate a variety of life processes, such as apoptosis. However, its role in CS-induced lung epithelial death has not been fully elucidated. Here we report that PRMT6 was decreased in mouse lung tissues from a cigarette smoke extract (CSE)-mediated experimental emphysematous model and in CSE treated or cigarette smoke exposed lung epithelial cells. Depletion of PRMT6 increased the protein levels of phosphatase PTEN and PI3K regulatory subunit p85 but decreased a downstream kinase PDK1, resulting in AKT dephosphorylation and thereafter, lung epithelial cell death. Knockout of PRMT6 inhibited epithelial survival and promoted CSE-mediated epithelial cell death, while ectopic expression of PRMT6 protein partially reversed epithelial cell death via PI3K/AKT-mediated cell survival signaling in CSE cellular models. These findings demonstrate that PRMT6 plays a crucial role in CS-induced bronchial epithelial cell death that may be a potential therapeutic target against the airway cell death in CS-induced COPD.

Citing Articles

NF-κB-mediated EAAT3 upregulation in antioxidant defense and ferroptosis sensitivity in lung cancer.

Wen D, Li W, Song X, Hu M, Liao Y, Xu D Cell Death Dis. 2025; 16(1):124.

PMID: 39987248 PMC: 11847022. DOI: 10.1038/s41419-025-07453-y.


Protective effects of sesamol against cigarette smoke toxicity on the blood-brain barrier.

Koru I, Atasever-Arslan B BMC Complement Med Ther. 2025; 25(1):68.

PMID: 39987119 PMC: 11846467. DOI: 10.1186/s12906-025-04796-z.


Ginkgo biloba extract alleviates CCl-induced acute liver injury by regulating PI3K/AKT signaling pathway.

Pu X, Fu Y, Yang Y, Xu G Heliyon. 2024; 10(4):e26093.

PMID: 38390084 PMC: 10881365. DOI: 10.1016/j.heliyon.2024.e26093.


SARS-CoV-2 Accessory Protein Orf7b Induces Lung Injury via c-Myc Mediated Apoptosis and Ferroptosis.

Deshpande R, Li W, Li T, Fanning K, Clemens Z, Nyunoya T Int J Mol Sci. 2024; 25(2).

PMID: 38256231 PMC: 10816122. DOI: 10.3390/ijms25021157.


CSE reduces OTUD4 triggering lung epithelial cell apoptosis via PAI-1 degradation.

Luo L, Li T, Zeng Z, Li H, He X, Chen Y Cell Death Dis. 2023; 14(9):614.

PMID: 37726265 PMC: 10509146. DOI: 10.1038/s41419-023-06131-1.


References
1.
Messner B, Frotschnig S, Steinacher-Nigisch A, Winter B, Eichmair E, Gebetsberger J . Apoptosis and necrosis: two different outcomes of cigarette smoke condensate-induced endothelial cell death. Cell Death Dis. 2012; 3:e424. PMC: 3542598. DOI: 10.1038/cddis.2012.162. View

2.
Chen Y, Hanaoka M, Chen P, Droma Y, Voelkel N, Kubo K . Protective effect of beraprost sodium, a stable prostacyclin analog, in the development of cigarette smoke extract-induced emphysema. Am J Physiol Lung Cell Mol Physiol. 2009; 296(4):L648-56. DOI: 10.1152/ajplung.90270.2008. View

3.
Yoshida M, Minagawa S, Araya J, Sakamoto T, Hara H, Tsubouchi K . Involvement of cigarette smoke-induced epithelial cell ferroptosis in COPD pathogenesis. Nat Commun. 2019; 10(1):3145. PMC: 6637122. DOI: 10.1038/s41467-019-10991-7. View

4.
Gao T, Furnari F, Newton A . PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth. Mol Cell. 2005; 18(1):13-24. DOI: 10.1016/j.molcel.2005.03.008. View

5.
Yao H, Rahman I . Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease. Toxicol Appl Pharmacol. 2011; 254(2):72-85. PMC: 3107364. DOI: 10.1016/j.taap.2009.10.022. View