Effect of beta-alanine treatment on mitochondrial taurine level and 5-taurinomethyluridine content.

Publisher: BioMed Central Country of Publication: England NLM ID: 9421567 Publication Model: Electronic Cited Medium: Internet ISSN: 1423-0127 (Electronic) Linking ISSN: 10217770 NLM ISO Abbreviation: J Biomed Sci Subsets: MEDLINE

Publication: 2009- : London : BioMed Central
Original Publication: Basel ; New York : S. Karger Medical and Scientific Publishers, c1994-

Mitochondria/*drug effects ; Mitochondria/*metabolism ; Taurine/*metabolism ; Uridine/*analogs & derivatives ; beta-Alanine/*pharmacology; Animals ; Cells, Cultured ; Humans ; Mitochondria/genetics ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/drug effects ; Myocytes, Cardiac/metabolism ; RNA, Transfer, Leu/metabolism ; Rats ; Rats, Wistar ; Uridine/metabolism

Background: The beta-amino acid, taurine, is a nutritional requirement in some species. In these species, the depletion of intracellular stores of taurine leads to the development of severe organ dysfunction. The basis underlying these defects is poorly understood, although there is some suggestion that oxidative stress may contribute to the abnormalities. Recent studies indicate that taurine is required for normal mitochondrial protein synthesis and normal electron transport chain activity; it is known that defects in these events can lead to severe mitochondrial oxidative stress. The present study examines the effect of taurine deficiency on the first step of mitochondrial protein synthesis regulation by taurine, namely, the formation of taurinomethyluridine containing tRNA.
Methods: Isolated rat cardiomyocytes were rendered taurine deficient by incubation with medium containing the taurine transport inhibitor, beta-alanine. The time course of cellular and mitochondrial taurine depletion was measured. The primer extension method was employed to evaluate the effect of beta-alanine treatment on taurinomethyluridine content of tRNALeu. The protein levels of ND6 were also determined by Western blot analysis.
Results: beta-alanine caused a time-dependent decrease in cellular taurine content, which were reduced in half after 48 hrs of incubation. The amount of taurine in the mitochondria was considerably less than that in the cytosol and was unaffected by beta-alanine treatment. Approximately 70% of the tRNALeu in the untreated cell lacked taurinomethyluridine and these levels were unchanged following beta-alanine treatment. Protein content of ND6, however, was significantly reduced after 48 hours incubation with beta-alanine.
Conclusions: The taurine levels of the cytosol and the mitochondria are not directly coupled. The beta-alanine-mediated reduction in taurine levels is too small to affect taurinomethyluridine levels. Nonetheless, it interferes with mitochondrial protein synthesis, as exemplified by a decrease in ND6 protein content. Thus, beta-alanine does not cause alterations in mitochondrial protein synthesis through the lowering of taurine levels.

Can J Physiol Pharmacol. 2009 Feb;87(2):91-9. (PMID: 19234572)
J Clin Invest. 1994 Feb;93(2):606-14. (PMID: 8113398)
J Nutr. 1972 Jul;102(7):805-14. (PMID: 4556121)
Science. 1987 Aug 14;237(4816):764-8. (PMID: 3616607)
Cardiovasc Res. 1993 Mar;27(3):358-63. (PMID: 7683972)
Am J Physiol. 1991 Jul;261(1 Pt 2):H121-7. (PMID: 1858911)
Circ Res. 1994 Jun;74(6):1210-9. (PMID: 8187287)
Amino Acids. 2000;19(3-4):527-46. (PMID: 11140357)
Adv Exp Med Biol. 1998;442:449-60. (PMID: 9635062)
Biochem Pharmacol. 1986 Mar 15;35(6):985-9. (PMID: 3082336)
FEMS Microbiol Lett. 2003 Sep 26;226(2):195-202. (PMID: 14553911)
Am J Physiol. 1997 Oct;273(4):H1956-61. (PMID: 9362266)
Neurochem Res. 1992 Aug;17(8):821-4. (PMID: 1641065)
J Nutr. 1978 May;108(5):773-8. (PMID: 641594)
Proc Natl Acad Sci U S A. 2005 May 17;102(20):7127-32. (PMID: 15870203)
Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15070-5. (PMID: 15477592)
Biochem J. 2006 Mar 15;394(Pt 3):699-706. (PMID: 16318624)
Am J Physiol. 1993 Apr;264(4 Pt 2):H1323-6. (PMID: 8476107)
EMBO J. 2002 Dec 2;21(23):6581-9. (PMID: 12456664)
Neurochem Res. 2004 Jan;29(1):247-55. (PMID: 14992284)
J Nutr. 1982 Dec;112(12):2293-300. (PMID: 7143111)
Pediatr Res. 1987 Apr;21(4):399-403. (PMID: 3106924)
J Biol Chem. 2002 Oct 18;277(42):39266-73. (PMID: 12163498)
Adv Exp Med Biol. 2003;526:307-21. (PMID: 12908615)
Biochem J. 1988 Nov 15;256(1):251-5. (PMID: 2851980)
Science. 1975 May 30;188(4191):949-51. (PMID: 1138364)
Amino Acids. 1995 Sep;8(3):231-46. (PMID: 24186401)
Adv Exp Med Biol. 2000;483:57-69. (PMID: 11787642)
Biol Neonate. 1989;56(4):186-91. (PMID: 2804183)
Physiol Rev. 1993 Jan;73(1):119-47. (PMID: 8419963)
Physiol Rev. 1992 Jan;72(1):101-63. (PMID: 1731369)
Am J Physiol Cell Physiol. 2002 May;282(5):C1113-20. (PMID: 11940527)
Amino Acids. 1998;15(1-2):135-42. (PMID: 9871493)
Am J Physiol Heart Circ Physiol. 2003 Dec;285(6):H2364-72. (PMID: 12919932)
Biochim Biophys Acta. 2000 Dec 20;1509(1-2):324-34. (PMID: 11118543)
J Neurosci Res. 1986;15(2):223-39. (PMID: 2421007)

0 (5-taurinomethyluridine)
0 (RNA, Transfer, Leu)
11P2JDE17B (beta-Alanine)
1EQV5MLY3D (Taurine)
WHI7HQ7H85 (Uridine)

Date Created: 20100901 Date Completed: 20110201 Latest Revision: 20211020

20221213

PMC2994391

10.1186/1423-0127-17-S1-S25

20804600