TY - JOUR
T1 - AVP induces myogenesis through the transcriptional activation of the myocyte enhancer factor 2
AU - Scicchitano, Bianca Maria
AU - Spath, Lucia
AU - Musarò, Antonio
AU - Molinaro, Mario
AU - Adamo, Sergio
AU - Nervi, Clara
PY - 2002
Y1 - 2002
N2 - The neurohypophyseal nonapeptide Arg8 vasopressin (AVP) promotes differentiation of cultured L6 and L5 myogenic cell lines and mouse primary satellite cells. Here, we investigated the molecular mechanism involved in the induction of the myogenic program by AVP. In L6 cells, AVP treatment rapidly induces Myf-5, myogenin, and myocyte enhancer factor 2 (MEF2) mRNAs, without affecting the expression of known myogenic growth factors such as IGF-I, IGF-II, or their receptors. In the presence of cycloheximide, AVP up-regulates the expression of MEF2, but not of myogenin, indicating that the synthesis of a protein intermediate is not necessary for MEF2 induction. Notably, AVP treatment activates a calcium/calmodulin kinase signaling pathway that induces cytosolic compartmentalization of the histone deacetylase 4, a mechanism related to the transcriptional activation of MEF2. The activity of chloramphenicol acetyltransferase reporter constructs carrying the Myo184 and Myo84 fragments of the myogenin promoter is also induced by AVP. Mutation of the MEF2 site completely abolishes the response to AVP, whereas deletion of the E1 site present in pMyo84 does not impair this response. Together, these results show that AVP induces myogenic differentiation through the transcriptional activation of MEF2, a mechanism that is critical for myogenesis
AB - The neurohypophyseal nonapeptide Arg8 vasopressin (AVP) promotes differentiation of cultured L6 and L5 myogenic cell lines and mouse primary satellite cells. Here, we investigated the molecular mechanism involved in the induction of the myogenic program by AVP. In L6 cells, AVP treatment rapidly induces Myf-5, myogenin, and myocyte enhancer factor 2 (MEF2) mRNAs, without affecting the expression of known myogenic growth factors such as IGF-I, IGF-II, or their receptors. In the presence of cycloheximide, AVP up-regulates the expression of MEF2, but not of myogenin, indicating that the synthesis of a protein intermediate is not necessary for MEF2 induction. Notably, AVP treatment activates a calcium/calmodulin kinase signaling pathway that induces cytosolic compartmentalization of the histone deacetylase 4, a mechanism related to the transcriptional activation of MEF2. The activity of chloramphenicol acetyltransferase reporter constructs carrying the Myo184 and Myo84 fragments of the myogenin promoter is also induced by AVP. Mutation of the MEF2 site completely abolishes the response to AVP, whereas deletion of the E1 site present in pMyo84 does not impair this response. Together, these results show that AVP induces myogenic differentiation through the transcriptional activation of MEF2, a mechanism that is critical for myogenesis
KW - Animals
KW - Arginine Vasopressin
KW - Calcium
KW - Cell Line
KW - DNA-Binding Proteins
KW - Electrophoretic Mobility Shift Assay
KW - MEF2 Transcription Factors
KW - Muscle Development
KW - Muscle Proteins
KW - Myogenic Regulatory Factor 5
KW - Myogenic Regulatory Factors
KW - Myogenin
KW - Promoter Regions, Genetic
KW - RNA, Messenger
KW - Rats
KW - Response Elements
KW - Trans-Activators
KW - Transcription Factors
KW - Transcriptional Activation
KW - Up-Regulation
KW - Animals
KW - Arginine Vasopressin
KW - Calcium
KW - Cell Line
KW - DNA-Binding Proteins
KW - Electrophoretic Mobility Shift Assay
KW - MEF2 Transcription Factors
KW - Muscle Development
KW - Muscle Proteins
KW - Myogenic Regulatory Factor 5
KW - Myogenic Regulatory Factors
KW - Myogenin
KW - Promoter Regions, Genetic
KW - RNA, Messenger
KW - Rats
KW - Response Elements
KW - Trans-Activators
KW - Transcription Factors
KW - Transcriptional Activation
KW - Up-Regulation
UR - http://hdl.handle.net/10807/97041
U2 - 10.1210/mend.16.6.0854
DO - 10.1210/mend.16.6.0854
M3 - Article
SN - 0888-8809
VL - 16
SP - 1407
EP - 1416
JO - Molecular Endocrinology
JF - Molecular Endocrinology
ER -