LKB1 signaling is altered in skeletal muscle of a Duchenne muscular dystrophy mouse model.

Autor:	Boccanegra B; Department of Pharmacy-Drug Sciences, University of Bari 'Aldo Moro', 70125 Bari, Italy., Mantuano P; Department of Pharmacy-Drug Sciences, University of Bari 'Aldo Moro', 70125 Bari, Italy., Conte E; Department of Pharmacy-Drug Sciences, University of Bari 'Aldo Moro', 70125 Bari, Italy., Cerchiara AG; Department of Pharmacy-Drug Sciences, University of Bari 'Aldo Moro', 70125 Bari, Italy., Tulimiero L; Department of Pharmacy-Drug Sciences, University of Bari 'Aldo Moro', 70125 Bari, Italy., Quarta R; Department of Pharmacy-Drug Sciences, University of Bari 'Aldo Moro', 70125 Bari, Italy., Caputo E; Department of Pharmacy-Drug Sciences, University of Bari 'Aldo Moro', 70125 Bari, Italy., Sanarica F; Department of Pharmacy-Drug Sciences, University of Bari 'Aldo Moro', 70125 Bari, Italy., Forino M; Preclinical R&D Department, Italfarmaco S.p.A., Cinisello Balsamo, 20092 Milan, Italy., Spadotto V; Preclinical R&D Department, Italfarmaco S.p.A., Cinisello Balsamo, 20092 Milan, Italy., Cappellari O; Department of Pharmacy-Drug Sciences, University of Bari 'Aldo Moro', 70125 Bari, Italy., Fossati G; Preclinical R&D Department, Italfarmaco S.p.A., Cinisello Balsamo, 20092 Milan, Italy., Steinkühler C; Preclinical R&D Department, Italfarmaco S.p.A., Cinisello Balsamo, 20092 Milan, Italy., De Luca A; Department of Pharmacy-Drug Sciences, University of Bari 'Aldo Moro', 70125 Bari, Italy.
Jazyk:	angličtina
Zdroj:	Disease models & mechanisms [Dis Model Mech] 2023 Jul 01; Vol. 16 (7). Date of Electronic Publication: 2023 Jul 10.
DOI:	10.1242/dmm.049930
Abstrakt:	The potential role of liver kinase B1 (LKB1) in the altered activation of the master metabolic and epigenetic regulator adenosine monophosphate-activated protein kinase (AMPK) in Duchenne muscular dystrophy has not been investigated so far. Hence, we analyzed both gene and protein levels of LKB1 and its related targets in gastrocnemius muscles of adult C57BL/10 mdx mice and D2 mdx mice, a model with a more severe dystrophic phenotype, as well as the sensitivity of the LKB1-AMPK pathway to AMPK activators, such as chronic exercise. Our data show, for the first time, a reduction in the levels of LKB1 and accessory proteins, MO25 and STRADα, in both mdx strains versus the respective wild type, which was further impaired by exercise, in parallel with a lack of further phosphorylation of AMPK. The AMPK-like kinase salt-inducible kinase (SIK) and class II histone deacetylases, along with expression of the HDAC target gene Mef2c, were also altered, supporting an impairment of LKB1-SIK-class II histone deacetylase signaling. Our results demonstrate that LKB1 may be involved in dystrophic progression, paving the way for future preclinical studies. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2023. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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