NDLI: Overexpression of IκBα in cardiomyocytes alleviates hydrogen peroxide-induced apoptosis and autophagy by inhibiting NF-κB activation

Content Provider	Springer Nature : BioMed Central
Author	Han, Min Chen, Xiao-Cui Sun, Ming-Hui Gai, Min-Tao Yang, Yi-Ning Gao, Xiao-Ming Ma, Xiang Chen, Bang-Dang Ma, Yi-Tong
Abstract	Background Inflammation and oxidative stress play predominant roles in the initiation and progression of ischaemia/reperfusion (I/R) injury, with nuclear factor kappa B (NF-κB) serving as a crucial mediator. Overexpression of the inhibitor of κB alpha (IκBα) gene is hypothesized to have protective effects against apoptosis and autophagy in cardiomyocytes subjected to hydrogen peroxide (H2O2) by inhibiting the NF-κB pathway. Methods The IκBαS32A, S36A gene was transfected via adeno-associated virus serotype 9 (AAV9) delivery into neonatal rat ventricular cardiomyocytes (NRVMs) prior to H2O2 treatment. NRVMs were divided into control, H2O2, GFP + H2O2, IκBα+H2O2, and pyrrolidine dithiocarbamate (PDTC) + H2O2 groups. Nuclear translocation of the NF-κB p65 subunit was evaluated by immunofluorescence and Western blotting. Cell viability was assessed by Cell Counting Kit-8 assay. Supernatant lactate dehydrogenase (LDH) and intracellular malondialdehyde (MDA) were measured to identify H2O2-stimulated cytotoxicity. Apoptosis was determined by Annexin V-PE/7-AAD staining, and the mitochondrial membrane potential (ΔΨm) was detected by JC-1 staining. Western blotting was used to detect apoptosis- and autophagy-related proteins. Results IκBα transfection significantly increased cell viability and ΔΨm but decreased the supernatant LDH and cellular MDA levels in cardiomyocytes exposed to H2O2. Meanwhile, IκBα overexpression decreased H2O2-induced apoptosis by upregulating the Bcl-2/Bax ratio and reduced autophagy by downregulating the expression of Beclin-1 and the LC3-II/LC3-I ratio. These effects partly accounted for the ability of IκBα to inhibit the NF-κB signalling pathway, as evidenced by decreases in p65 phosphorylation and nuclear translocation. Indeed, the effects of inactivation of NF-κB signalling with the specific inhibitor PDTC resembled the cardioprotective effects of IκBα during H2O2 stimulation. Conclusion IκBα overexpression can ameliorate H2O2-induced apoptosis, autophagy, oxidative injury, and ΔΨm loss through inhibition of the NF-κB signalling pathway. These findings suggest that IκBα transfection can result in successful resistance to oxidative stress-induced damage by inhibiting NF-κB activation, which may provide a potential therapeutic target for the prevention of myocardial I/R injury.
Related Links	https://lipidworld.biomedcentral.com/counter/pdf/10.1186/s12944-020-01327-2.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s12944-020-01327-2
Journal	Lipids in Health and Disease
Issue Number	1
Volume Number	19
Language	English
Publisher	BioMed Central
Publisher Date	2020-06-24
Access Restriction	Open
Subject Keyword	Lipidology Medical Biochemistry Clinical Nutrition Nuclear factor kappa B Inhibitor of kappa B alpha Apoptosis Autophagy Adeno-associated virus serotype 9 Oxidative stress Cardiomyocytes
Content Type	Text
Resource Type	Article
Subject	Endocrinology Clinical Biochemistry Endocrinology, Diabetes and Metabolism Biochemistry (medical)
Journal Impact Factor	3.9/2023
5-Year Journal Impact Factor	4.3/2023

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