title: Differential expression of 26S proteasome subunits and functional activity during neonatal development.
abstract: Proteasomes regulate many essential cellular processes by degrading intracellular proteins. While aging is known to be associated with dysfunction of the proteasome, there are few reports detailing activity and function of proteasomes in the early stages of life. To elucidate the function and development of mammalian proteasomes, 26S proteasomes were affinity-purified from rat intestine, spleen and liver. The developmental expression of core, regulatory and immunoproteasome subunits was analyzed by immunoblotting and reverse-transcriptase PCR of mRNA subunits, and proteasome catalytic function was determined by fluorogenic enzymatic assays. The expression of core (β2, β5, α7 and β1) and regulatory (Rpt5) subunits was found to be present at low levels at birth and increased over time particularly at weaning. In contrast, while gradual developmental progression of proteasome structure was also seen with the immunoproteasome subunits (β1i, β5i, and β2i), these were not present at birth. Our studies demonstrate a developmental pattern to 26S proteasome activity and subunit expression, with low levels of core proteasome components and absence of immunoproteasomes at birth followed by increases at later developmental stages. This correlates with findings from other studies of a developmental hyporesponsiveness of the adaptive immune system to allow establishment of microbial colonization immediately after birth.
authors.affiliation: Departments of Pediatrics and Medicine, University of Chicago, Chicago, IL 60611, USA. eclaud@peds.bsd.uchicago.edu.
authors.forename: Erika C
authors.initials: EC
authors.lastname: Claud
authors.affiliation: Gastrointestinal Diseases Research Unit, Department of Medicine, Queen's University, Kingston, ON K7L 2V7, Canada. jm13@queensu.ca.
authors.forename: Julie A K
authors.initials: JA
authors.lastname: McDonald
authors.affiliation: Gastrointestinal Diseases Research Unit, Department of Medicine, Queen's University, Kingston, ON K7L 2V7, Canada. smh6@queensu.ca.
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: He
authors.affiliation: Departments of Pediatrics and Medicine, University of Chicago, Chicago, IL 60611, USA. yyu@peds.bsd.uchicago.edu.
authors.forename: Yueyue
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Gastrointestinal Diseases Research Unit, Department of Medicine, Queen's University, Kingston, ON K7L 2V7, Canada. 9ld27@queensu.ca.
authors.forename: Lily
authors.initials: L
authors.lastname: Duong
authors.affiliation: Department of Biochemistry, Rush University, Chicago, IL 60612, USA. Jun_Sun@rush.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
authors.affiliation: Gastrointestinal Diseases Research Unit, Department of Medicine, Queen's University, Kingston, ON K7L 2V7, Canada. eop@queensu.ca.
authors.forename: Elaine O
authors.initials: EO
authors.lastname: Petrof
mesh_terms: D056704:Adaptive Immunity; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002918:Chymotrypsin / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006868:Hydrolysis; D009928:Organ Specificity; D011247:Pregnancy; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014357:Trypsin / Q000378:metabolism; D014886:Weaning
chemical_list: D021122:Protein Subunits; D002918:Chymotrypsin; D014357:Trypsin; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D000251:Adenosine Triphosphatases