Prosaposin is immunolocalized to muscle and prosaptides promote myoblast fusion and attenuate loss of muscle mass after nerve injury.
Prosaposin is the precursor of the saposins and has both neurotrophic and myelinotrophic activity in vitro and in vivo. Using an antibody specific for the holoprotein, an immunocytochemical survey demonstrated intense staining of adult rat skeletal, cardiac, and smooth muscle cells. Prosaposin immunoreactivity in muscle appears dependent on innervation, as denervated adult rat skeletal muscles showed decreased immunostaining that returned to normal levels after reinnervation. TX14(A), a peptide derived from the neurotrophic sequence of prosaposin, attenuated the decline in muscle mass loss following nerve injury induced by a constricting ligature. In vitro, both L6 myoblasts and primary chick-embryo myoblasts showed similar prosaposin immunopositivity, mainly in myotubes. TX14(A) induced a threefold increase in L6 myoblast fusion during early stages of differentiation without affecting cell proliferation. The fusion process was decreased in vitro in a dose-dependent fashion by addition of a neutralizing anti-prosaposin antibody. These data suggest that, in addition to neurotrophic and myelinotrophic activities, prosaposin has myotrophic properties.
Rende
M
M
Section of Anatomy, Department of Experimental Medicine and Biochemical Sciences, University of Perugia School of Medicine, Via del Giochetto, 06122 Perugia, Italy. rende@unipg.it
Brizi
E
E
Donato
R
R
Provenzano
C
C
Bruno
R
R
Mizisin
A P
AP
Garrett
R S
RS
Calcutt
N A
NA
Campana
W M
WM
O'Brien
J S
JS
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002459:Cell Fusion; D002460:Cell Line; D002642:Chick Embryo; D005260:Female; D006023:Glycoproteins / Q000032:analysis* / Q000737:chemistry; D007074:Immunoglobulin G / Q000494:pharmacology; D007150:Immunohistochemistry; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000166:cytology; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009206:Myocardium / Q000166:cytology; D009414:Nerve Growth Factors / Q000737:chemistry / Q000494:pharmacology*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D011498:Protein Precursors / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D049231:Saposins; D012584:Sciatic Nerve / Q000502:physiology*
D000906:Antibodies; D006023:Glycoproteins; D007074:Immunoglobulin G; D009414:Nerve Growth Factors; D009842:Oligopeptides; D011498:Protein Precursors; C483347:Psap protein, rat; D049231:Saposins; C101246:prosaptide