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Literature summary for 2.7.1.138 extracted from

  • Kukreti, H.; Amuthavalli, K.
    MicroRNA-34a causes ceramide accumulation and effects insulin signaling pathway by targeting ceramide kinase (CERK) in aging skeletal muscle (2020), J. Cell. Biochem., 121, 3070-3089 .
    View publication on PubMed

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + ceramide Mus musculus
-
ADP + ceramide 1-phosphate
-
?
ATP + ceramide Mus musculus C57BL/6J
-
ADP + ceramide 1-phosphate
-
?

Organism

Organism UniProt Comment Textmining
Mus musculus Q8K4Q7
-
-
Mus musculus C57BL/6J Q8K4Q7
-
-

Source Tissue

Source Tissue Comment Organism Textmining
C2C12 cell
-
Mus musculus
-
myoblast
-
Mus musculus
-
skeletal muscle analysis of levels of miR-34a, ceramide kinase (CERK) and other insulin signaling molecules in skeletal muscle from old mice. miR-34a is elevated in the muscles of 2-year-old mice Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + ceramide
-
Mus musculus ADP + ceramide 1-phosphate
-
?
ATP + ceramide
-
Mus musculus C57BL/6J ADP + ceramide 1-phosphate
-
?

Synonyms

Synonyms Comment Organism
CERK
-
Mus musculus

Cofactor

Cofactor Comment Organism Structure
ATP
-
Mus musculus

General Information

General Information Comment Organism
malfunction miR-34a targets CERK resulting in ceramide accumulation, activation of PP2A and the pJNK pathway in muscle and C2C12 myoblasts. Overexpression of miR-34a in C2C12 myoblasts leads to alterations in the insulin signaling pathway, which are rescued by its antagonism Mus musculus
metabolism myostatin (Mstn) and microRNA miR-34a antagonism can help ameliorate ceramide accumulation and loss of insulin sensitivity in aging skeletal muscle Mus musculus
physiological function myostatin (Mstn) levels increase in aging mouse muscle and upregulate miR-34a, which inhibits CERK resulting in increased ceramide levels. This ceramide accumulation activates PP2A and pJNK causing hypophosphorylation of AKT and hyperphosphorylation of IRS1 (Ser307), respectively, impairing insulin signaling pathway and eventually inhibiting the sarcolemma localization of GLUT4. These changes can result in reduced glucose uptake and insulin resistance. CERK inhibition affects insulin signaling pathway in C2C12 myoblasts via ceramide accumulation. CERK inhibition with NVP231 results in hypophosphorylation of insulin signaling molecules (PI3K, AKT, AS160, and GSK3b) and hyperphosphorylation of IRS1 (Ser307) when compared with dimethyl sulfoxide treated control C2C12 myoblasts Mus musculus