Expression and localization of augmenter of liver regeneration in human muscle tissue.
Mitochondrial DNA (mt-DNA) disorders and abnormal regulation of nuclear-derived proteins devoted to the cross-talk between the two cellular genomes have recently interested researchers in the field of neuromuscular diseases. We have identified, isolated and sequenced a new gene, augmenter of liver regeneration (ALR) that stimulates in vivo hepatocyte proliferation and up-regulates mt-DNA expression and ATP production. ALR protein (Alrp) is mainly located, in rat, in the mitochondrial inter-membrane space and its mRNA is particularly abundant in brain, muscle, testis and liver, tissues whose activity is mostly dependent on mitochondrial metabolism. Studies on rat Alrp sequence revealed the presence of homologous amino-acid sections into proteins derived from mouse, human, Drosophyla, plants and even DNA viruses. In this article, we evaluated ALR expression in normal human muscular tissues, both as protein and as mRNA. The data, obtained by molecular biology, immunohistochemistry and electron microscopy, demonstrated that: (i) Alrp and ALR mRNA are present in human muscular tissue; (ii) Alrp is particularly expressed in muscular fibres rich in mitochondria; (iii) Alrp is localized in the mitochondrial inter-membrane space or associated to mitochondrial cristae; and (iv) in subjects younger then 35 years of age, ALR mRNA expression is different between male and female subjects. In conclusion, the present data set Alrp, as a factor associated with mitochondria also in human tissue, call for future studies aimed at establishing Alrp as an important factor involved in the molecular events that trigger neuromuscular diseases.
Polimeno
Lorenzo
L
Section of Gastroenterology, Department of Emergency and Organ Transplantation (DETO), School of Pharmacy, University of Bari, 70124 Bari, Italy.
Pesetti
Barbara
B
Giorgio
Floriana
F
Moretti
Biagio
B
Resta
Leonardo
L
Rossi
Roberta
R
Annoscia
Emanuele
E
Patella
Vittorio
V
Notarnicola
Angela
A
Mallamaci
Rosanna
R
Francavilla
Antonio
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003579:Cytochrome Reductases / Q000032:analysis* / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000737:chemistry; D051336:Mitochondrial Membranes / Q000737:chemistry; D024101:Mitochondrial Proteins / Q000032:analysis; D018482:Muscle, Skeletal / Q000737:chemistry*; D050862:Oxidoreductases Acting on Sulfur Group Donors; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D055815:Young Adult
D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D003579:Cytochrome Reductases; C500897:GFER protein, human; D050862:Oxidoreductases Acting on Sulfur Group Donors