Impairment of intracellular antiviral defense with age: age-dependent changes in expression of interferon-induced and double-stranded RNA-activated 2-5A synthetase in rat.

Abstract

The 2',5'-oligoadenylate (2-5A) system is involved in the defense of mammalian cells against virus infection. In a previous study [25], we demonstrated that the activities of the enzymes which synthesize and degrade 2-5A [2-5A synthetase (2-5OAS) and 2',3'-exoribonuclease] and of the enzyme that is activated by 2-5A (ribonuclease L) change during aging and development in different tissues of rat. The age-dependent decrease in 2-5OAS activity and increase in 2-5A nuclease activity results in a decrease in the cellular 2-5A content, suggesting that the efficiency of the antiviral 2-5A system is impaired in aged rats. Here we determined the age-dependent changes in the level of mRNA coding for the class I isoenzyme of 2-5OAS (M(r) 40-46 kDa) in rat liver and brain using a cDNA which was recently cloned from rat hippocampus. We found that the decrease in 2-5OAS activity is accompanied by a decrease in the level of 2-5OAS mRNA; in old animals (32-33 months old), the amount of 2-5OAS mRNA was reduced to 20-30% compared to young adult (2-3 months old) (100%) and middle-aged adult animals (12 months old) (110-120%). In addition, Western-blotting experiments revealed that the amount of class I 2-5OAS capable of binding to its activator, poly(I).poly(C), is also diminished in the livers and brains of old rats compared to those of young adult and middle-aged adult animals.

• Authors: A Kuusksalu, E Truve, A Aaspollu, M Kelve, U Scheffer, W E Müller, H C Schröder
• Journal: Mechanisms of ageing and development (Mech Ageing Dev) Vol. 78 Issue 2 Pg. 103-15 (Mar 01 1995) ISSN: 0047-6374 [Print] Ireland
• PMID: 7541098 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Double-Stranded
• RNA, Messenger
• Interferons
• Protein Kinases
• 2',5'-Oligoadenylate Synthetase

Topics

• 2',5'-Oligoadenylate Synthetase (biosynthesis)
• Age Factors
• Aging (metabolism, physiology)
• Amino Acid Sequence
• Animals
• Blotting, Western
• Brain (enzymology)
• Female
• Interferons (genetics)
• Liver (enzymology)
• Molecular Sequence Data
• Protein Kinases (metabolism)
• RNA, Double-Stranded (genetics, metabolism)
• RNA, Messenger (metabolism)
• Rats
• Virus Diseases (metabolism)