LKB1 signaling is altered in skeletal muscle of a Duchenne muscular dystrophy mouse model
© 2023. Published by The Company of Biologists Ltd..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
|---|---|
| Enthalten in: |
Disease models & mechanisms - 16(2023), 7 vom: 01. Juli |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Boccanegra, Brigida [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 12.07.2023 Date Revised 21.07.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1242/dmm.049930 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM359284981 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM359284981 | ||
| 003 | DE-627 | ||
| 005 | 20231226080539.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1242/dmm.049930 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1197.xml |
| 035 | |a (DE-627)NLM359284981 | ||
| 035 | |a (NLM)37427454 | ||
| 035 | |a (PII)dmm049930 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Boccanegra, Brigida |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a LKB1 signaling is altered in skeletal muscle of a Duchenne muscular dystrophy mouse model |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 12.07.2023 | ||
| 500 | |a Date Revised 21.07.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. Published by The Company of Biologists Ltd. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a AMPK | |
| 650 | 4 | |a Duchenne muscular dystrophy | |
| 650 | 4 | |a Epigenetic | |
| 650 | 4 | |a LKB1 | |
| 650 | 4 | |a Mouse models | |
| 650 | 4 | |a Muscle metabolism | |
| 650 | 7 | |a AMP-Activated Protein Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.31 |2 NLM | |
| 650 | 7 | |a Protein Serine-Threonine Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Stk11 protein, mouse |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 700 | 1 | |a Mantuano, Paola |e verfasserin |4 aut | |
| 700 | 1 | |a Conte, Elena |e verfasserin |4 aut | |
| 700 | 1 | |a Cerchiara, Alessandro Giovanni |e verfasserin |4 aut | |
| 700 | 1 | |a Tulimiero, Lisamaura |e verfasserin |4 aut | |
| 700 | 1 | |a Quarta, Raffaella |e verfasserin |4 aut | |
| 700 | 1 | |a Caputo, Erika |e verfasserin |4 aut | |
| 700 | 1 | |a Sanarica, Francesca |e verfasserin |4 aut | |
| 700 | 1 | |a Forino, Monica |e verfasserin |4 aut | |
| 700 | 1 | |a Spadotto, Valeria |e verfasserin |4 aut | |
| 700 | 1 | |a Cappellari, Ornella |e verfasserin |4 aut | |
| 700 | 1 | |a Fossati, Gianluca |e verfasserin |4 aut | |
| 700 | 1 | |a Steinkühler, Christian |e verfasserin |4 aut | |
| 700 | 1 | |a De Luca, Annamaria |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Disease models & mechanisms |d 2008 |g 16(2023), 7 vom: 01. Juli |w (DE-627)NLM184855462 |x 1754-8411 |7 nnns |
| 773 | 1 | 8 | |g volume:16 |g year:2023 |g number:7 |g day:01 |g month:07 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1242/dmm.049930 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 16 |j 2023 |e 7 |b 01 |c 07 | ||