JIP3 deficiency attenuates cardiac hypertrophy by suppression of JNK pathway
- Department of Cardiology, Linyi Central Hospital of Shandong Province, Linyi 276400 (China)
- Department of Geriatric Medicine, Linyi Central Hospital of Shandong Province, Linyi 276400 (China)
- Department of Cardiology, Shandong Provincial Hospital, Jinan 250021 (China)
Highlights: • JIP3 deficiency in mice alleviates pressure overload-induced hypertrophy. • Deletion of JIP3 attenuates aortic banding-induced cardiac oxidative stress, inflammation, apoptosis and ER stress. • Inhibition of JIP3-reduced cardiac hypertrophy is dependent on JNK inactivation. Pathological cardiac hypertrophy is a leading cause of morbidity and mortality worldwide; however, our understanding of the molecular mechanisms revealing the disease is still unclear. In the present study, we suggested that c-Jun N-terminal kinase (JNK)-interacting protein 3 (JIP3), involved in various cellular processes, played an essential role in regulating pathological cardiac hypertrophy through in vivo and in vitro studies. JIP3 was highly expressed in human hearts with hypertrophic cardiomyopathy (HCM), and in mouse hypertrophic hearts. Following, the wild type (WT) and JIP3-knockout (KO) mice subjected to aortic banding (AB) challenge were used as animal models with cardiac hypertrophy. The results showed that JIP3-KO mice after AB operation exhibited attenuated cardiac function, reduced fibrosis levels and decreased hypertrophic marker proteins, including atrial natriuretic peptides (Anp) and brain/B-type natriuretic peptides (Bnp) and β-myosin heavy chain (β-Mhc). Loss of JIP3 also ameliorated oxidative stress, inflammatory response, apoptosis and endoplasmic reticulum (ER) stress in hearts of mice after AB surgery. Consistently, the expressions of ER stress-related molecules, such as phosphorylated-α-subunit of the eukaryotic initiation factor-2 (eIF2α), glucose-regulated protein (GRP) 78 and C/-EBP homologous protein (CHOP), were markedly decreased by JIP3-deficiency in hearts of AB-operated mice. JNK and its down-streaming signal of p90rsk was highly activated by AB operation in WT mice, while being significantly reversed by JIP3-ablation. Intriguingly, the in vitro results showed that promoting JNK activation by using its activator of anisomycin enhanced AngII-stimulated ER stress, oxidative stress, apoptosis and inflammatory response in cardiomyocytes isolated from WT mice. However, JIP3-KO-attenuated these pathologies was rescued by anisomycin treatment in AngII-incubated cardiomyocytes. Together, the findings indicated that blockage of JIP3 could alleviate cardiac hypertrophy via inactivating JNK pathway, and thus might be a promising strategy to prevent pathological cardiac hypertrophy.
- OSTI ID:
- 23105697
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 503, Issue 1; Other Information: Copyright (c) 2018 Published by Elsevier Inc.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Interleukin-6 deficiency attenuates angiotensin II-induced cardiac pathogenesis with increased myocyte hypertrophy
DUSP14 knockout accelerates cardiac ischemia reperfusion (IR) injury through activating NF-κB and MAPKs signaling pathways modulated by ROS generation