Activation of endoproteolytic processing of insulin-like growth factor-II in fetal, early postnatal, and pregnant rats and persistence of circulating levels in postnatal life.
The process of posttranslational modifications of IGF-II likely has important physiological consequences. In addition to mature IGF-II, glycosylated proIGF-II(156-amino acid peptide) and two glycosylated big IGF-II forms, IGF-II(1-104) and IGF-II(1-87), have been identified in the human circulation. Due to lack of an appropriate methodology, different IGF-II isoforms have not been demonstrated and characterized in the rat circulation, thus preventing a better understanding of the physiological and pathological roles of IGF-II. In the present study, we characterized each IGF-II form and assessed its content in the rat circulation throughout life time by using a highly sensitive Western blot analysis, which is void of the IGF binding protein interference and distinguished all IGF-II forms. For the first time, we demonstrated the presence of IGF-II variants, including proIGF-II, IGF-II(1-87), and mature IGF-II, in the rat circulation during postnatal life, challenging the current impression that IGF-II is absent from sera of adult rats. ProIGF-II is glycosylated and is the predominant form in the rat circulation. Endoproteolytic processing of proIGF-II was clearly activated in fetal, neonatal, and pregnant rats, likely reflecting its involvement in fetal development through the generation of specific forms of IGF-II (e.g. mature IGF-II) that are required for their distinct biological functions. Taken together, our data also suggest that serum IGF-II profiles may reflect underlying physiological conditions.
Qiu
Qing
Q
Department of Obstetrics and Gynecology, The Ottawa Hospital, 501 Smyth Road, Ottawa, Ontario, Canada. qqiu@ohri.ca
Jiang
Jin-Yi
JY
Bell
Michael
M
Tsang
Benjamin K
BK
Gruslin
Andrée
A
D000375:Aging / Q000097:blood; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006031:Glycosylation; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood / Q000378:metabolism*; D011498:Protein Precursors / Q000097:blood / Q000235:genetics; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley
D011498:Protein Precursors; C066038:proinsulin-like growth factor II; D007335:Insulin-Like Growth Factor II; D010447:Peptide Hydrolases