Abstract
Our previous findings [Hazelton & Lang (1978) Fed. Proc. Fed. Am. Soc. Exp. Biol. 37(6), 2378 (abstr.)] demonstrated a senescence-specific decrease in glutathione (GSH) concentration in the yellow-fever mosquito Aedes aegypti (Louisville)]. As a possible mechanism for this change, GSH biosynthesis was investigated in adult mosquitoes of different ages through the life-span. Biosynthesis was measured as the incorporation rate of [14C]glycine or [14C]cystine into glutathione. Essential information to validate the procedure was also obtained on the precursor-amino-acid pool sizes and kinetic parameters such as lag-time and time course of incorporation. Also, synthesis de novo rather than exchange was verified using buthionine sulphoximine, a specific inhibitor of GSH biosynthesis. The synthetic rates with either amino acid precursor varied throughout the adult life-span, but the patterns for both precursors were essentially identical. Biosynthesis was high in the newly emerged adult and decreased 62-70% (P less than 0.005) to a plateau during maturity. From the mature value there was a decrease of 36-41% (P less than 0.005) to a new plateau during senescence. Glutathione biosynthesis and concentration were correlated throughout maturity and senescence (r = 0.982) and thus biosynthesis was proportional to glutathione content. On this basis we concluded that impaired biosynthesis is the major and perhaps sole mechanism for the aging decrease in glutathione content.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abraham E. C., Taylor J. F., Lang C. A. Influence of mouse age and erythrocyte age on glutathione metabolism. Biochem J. 1978 Sep 15;174(3):819–825. doi: 10.1042/bj1740819. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Du J. T., Beyer T. A., Lang C. A. Protein biosynthesis in aging mouse tissues. Exp Gerontol. 1977;12(5-6):181–191. doi: 10.1016/0531-5565(77)90004-3. [DOI] [PubMed] [Google Scholar]
- Griffith O. W., Meister A. Glutathione: interorgan translocation, turnover, and metabolism. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5606–5610. doi: 10.1073/pnas.76.11.5606. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Griffith O. W., Meister A. Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (S-n-butyl homocysteine sulfoximine). J Biol Chem. 1979 Aug 25;254(16):7558–7560. [PubMed] [Google Scholar]
- Hazelton G. A., Lang C. A. Glutathione S-transferase activities in the yellow-fever mosquito [Aedes aegypti (Louisville)] during growth and aging. Biochem J. 1983 Feb 15;210(2):281–287. doi: 10.1042/bj2100281. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hazelton G. A., Lang C. A. Glutathione contents of tissues in the aging mouse. Biochem J. 1980 Apr 15;188(1):25–30. doi: 10.1042/bj1880025. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kosower N. S., Kosower E. M. The glutathione status of cells. Int Rev Cytol. 1978;54:109–160. doi: 10.1016/s0074-7696(08)60166-7. [DOI] [PubMed] [Google Scholar]
- LANG C. A., LAU H. Y., JEFFERSON D. J. PROTEIN AND NUCLEIC ACID CHANGES DURING GROWTH AND AGING IN THE MOSQUITO. Biochem J. 1965 May;95:372–377. doi: 10.1042/bj0950372. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lauterburg B. H., Vaishnav Y., Stillwell W. G., Mitchell J. R. The effects of age and glutathione depletion on hepatic glutathione turnover in vivo determined by acetaminophen probe analysis. J Pharmacol Exp Ther. 1980 Apr;213(1):54–58. [PubMed] [Google Scholar]
- Lunn G., Dale G. L., Beutler E. Transport accounts for glutathione turnover in human erythrocytes. Blood. 1979 Jul;54(1):238–244. [PubMed] [Google Scholar]
- Meister A., Tate S. S. Glutathione and related gamma-glutamyl compounds: biosynthesis and utilization. Annu Rev Biochem. 1976;45:559–604. doi: 10.1146/annurev.bi.45.070176.003015. [DOI] [PubMed] [Google Scholar]
- Mills B. J., Lang C. A. The biosynthesis of deoxyribonucleic acid during the life-span of the mosquito. Biochem J. 1976 Feb 15;154(2):481–490. doi: 10.1042/bj1540481. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Minnich V., Smith M. B., Brauner M. J., Majerus P. W. Glutathione biosynthesis in human erythrocytes. I. Identification of the enzymes of glutathione synthesis in hemolysates. J Clin Invest. 1971 Mar;50(3):507–513. doi: 10.1172/JCI106519. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith J. E., Lee M. S., Mia A. S. Decreased gamma-glutamylcysteine synthetase: the probable cause of glutathione deficiency in sheep erythrocytes. J Lab Clin Med. 1973 Nov;82(5):713–718. [PubMed] [Google Scholar]
- Thayer D. W., Terzian L. A. Free amino acids and related compounds in the tissues of ageing female Aedes aegypti mosquitoes. J Insect Physiol. 1970 Jan;16(1):1–15. doi: 10.1016/0022-1910(70)90107-1. [DOI] [PubMed] [Google Scholar]