Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0026850 (
muscular dystrophy
)
5,870
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Mutations in lipin1 are suggested to be a common cause of massive rhabdomyolysis episodes in children; however, the molecular mechanisms involved in the regulation of myofiber death caused by the absence of lipin1 are not fully understood. Loss of membrane integrity is considered as an effective inducer of cell death in
muscular dystrophy
. In this study, we utilized a mouse line with selective homozygous lipin1 deficiency in the skeletal muscle (Lipin1
Myf5cKO
) to determine the role of compromised membrane integrity in the myofiber death in lipin1-deficient muscles. We found that Lipin1
Myf5cKO
muscles had significantly elevated proapoptotic factors (Bax, Bak, and cleaved caspase-9) and necroptotic proteins such as RIPK1, RIPK3, and
MLKL
compared with WT mice. Moreover, Lipin1
Myf5cKO
muscle had significantly higher membrane disruptions, as evidenced by increased IgG staining and elevated uptake of Evans Blue Dye (EBD) and increased serum creatine kinase activity in Lipin1
Myf5cKO
muscle fibers. EBD-positive fibers were strongly colocalized with apoptotic or necroptotic myofibers, suggesting an association between compromised plasma membrane integrity and cell death pathways. We further show that the absence of lipin1 leads to a significant decrease in the absolute and specific muscle force (normalized to muscle mass). Our work indicates that apoptosis and necroptosis are associated with a loss of membrane integrity in Lipin1
Myf5cKO
muscle and that myofiber death and dysfunction may cause a decrease in contractile force.
...
PMID:Loss of membrane integrity drives myofiber death in lipin1-deficient skeletal muscle. 3311 95
