TY - JOUR
T1 - Neprilysin participates in skeletal muscle regeneration and is accumulated in abnormal muscle fibres of inclusion body myositis.
AU - Broccolini, Aldobrando
AU - Gidaro, Teresa
AU - Morosetti, Roberta
AU - Gliubizzi, Carla
AU - Servidei, Tiziana
AU - Pescatori, Mario
AU - Tonali, Pietro Attilio
AU - Ricci, Enzo
AU - Mirabella, Massimiliano
PY - 2006
Y1 - 2006
N2 - Neprilysin (NEP, EP24.11), a metallopeptidase originally shown to modulate signalling events by degrading small regulatory peptides, is also an amyloid-beta- (Abeta) degrading enzyme. We investigated a possible role of NEP in inclusion body myositis (IBM) and other acquired and hereditary muscle disorders and found that in all myopathies NEP expression was directly associated with the degree of muscle fibre regeneration. In IBM muscle, NEP protein was also strongly accumulated in Abeta-bearing abnormal fibres. In vitro, during the experimental differentiation of myoblasts, NEP protein expression was regulated at the post-transcriptional level with a rapid increase in the early stage of myoblast differentiation followed by a gradual reduction thereafter, coincident with the progression of the myogenic programme. Treatment of differentiating muscle cells with the NEP inhibitor dl-3-mercapto-2-benzylpropanoylglycine resulted in impaired differentiation that was mainly associated with an abnormal regulation of Akt activation. Therefore, NEP may play an important role during muscle cell differentiation, possibly through the regulation, either directly or indirectly, of the insulin-like growth factor I-driven myogenic programme. In IBM muscle increased NEP may be instrumental in (i) reducing the Abeta accumulation in vulnerable fibres and (ii) promoting a repair/regenerative attempt of muscle fibres possibly through the modulation of insulin-like growth factor I-dependent pathways.
AB - Neprilysin (NEP, EP24.11), a metallopeptidase originally shown to modulate signalling events by degrading small regulatory peptides, is also an amyloid-beta- (Abeta) degrading enzyme. We investigated a possible role of NEP in inclusion body myositis (IBM) and other acquired and hereditary muscle disorders and found that in all myopathies NEP expression was directly associated with the degree of muscle fibre regeneration. In IBM muscle, NEP protein was also strongly accumulated in Abeta-bearing abnormal fibres. In vitro, during the experimental differentiation of myoblasts, NEP protein expression was regulated at the post-transcriptional level with a rapid increase in the early stage of myoblast differentiation followed by a gradual reduction thereafter, coincident with the progression of the myogenic programme. Treatment of differentiating muscle cells with the NEP inhibitor dl-3-mercapto-2-benzylpropanoylglycine resulted in impaired differentiation that was mainly associated with an abnormal regulation of Akt activation. Therefore, NEP may play an important role during muscle cell differentiation, possibly through the regulation, either directly or indirectly, of the insulin-like growth factor I-driven myogenic programme. In IBM muscle increased NEP may be instrumental in (i) reducing the Abeta accumulation in vulnerable fibres and (ii) promoting a repair/regenerative attempt of muscle fibres possibly through the modulation of insulin-like growth factor I-dependent pathways.
KW - Neprilysin
KW - muscle fibres
KW - myositis
KW - skeletal muscle regeneration
KW - Neprilysin
KW - muscle fibres
KW - myositis
KW - skeletal muscle regeneration
UR - http://hdl.handle.net/10807/8478
U2 - 10.1111/j.1471-4159.2005.03584.x
DO - 10.1111/j.1471-4159.2005.03584.x
M3 - Article
SN - 0022-3042
VL - 96
SP - 777
EP - 789
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
ER -