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Effect of the branched-chain alpha-keto acids accumulating in maple syrup urine disease on S100B release from glial cells.
J Neurol Sci. 2007 Sep 15; 260(1-2):87-94.JN

Abstract

Accumulation of the branched-chain alpha-keto acids (BCKA), alpha-ketoisocaproic acid (KIC), alpha-keto-beta-methylvaleric acid (KMV) and alpha-ketoisovaleric acid (KIV) and their respective branched-chain alpha-amino acids (BCAA) occurs in tissues and biological fluids of patients affected by the neurometabolic disorder maple syrup urine disease (MSUD). The objective of this study was to verify the effect of the BCKA on S100B release from C6 glioma cells. The cells were exposed to 1, 5 or 10 mM BCKA for different periods and the S100B release was measured afterwards. The results indicated that KIC and KIV, but not KMV, significantly enhanced S100B liberation after 6 h of exposure. Furthermore, the stimulatory effect of the BCKA on S100B release was prevented by coincubation with the energetic substrate creatine and with the N-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase inhibitor, indicating that energy deficit and nitric oxide (NO) were probably involved in this effect. Furthermore, the increase of S100B release was prevented by preincubation with the protein kinase inhibitors KN-93 and H-89, indicating that KIC and KIV altered Ca2+/calmodulin (PKCaMII)- and cAMP (PKA)-dependent protein kinases activities, respectively. In contrast, other antioxidants such as glutathione (GSH) and trolox (soluble vitamin E) were not able to prevent KIC- and KIV-induced increase of S100B liberation, suggesting that the alteration of S100B release caused by the BCKA is not mediated by oxidation of sulfydryl or other essential groups of the enzyme as well as by lipid peroxyl radicals. Considering the importance of S100B for brain regulation, it is conceivable that enhanced liberation of this protein by increased levels of BCKA may contribute to the neurodegeneration characteristic of MSUD patients.

Authors+Show Affiliations

Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, Rua Ramiro Barcelos 2600 anexo, 90035-003 Porto Alegre, RS, Brazil. csfunchal@yahoo.com.brNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17499767

Citation

Funchal, Cláudia, et al. "Effect of the Branched-chain Alpha-keto Acids Accumulating in Maple Syrup Urine Disease On S100B Release From Glial Cells." Journal of the Neurological Sciences, vol. 260, no. 1-2, 2007, pp. 87-94.
Funchal C, Tramontina F, Quincozes dos Santos A, et al. Effect of the branched-chain alpha-keto acids accumulating in maple syrup urine disease on S100B release from glial cells. J Neurol Sci. 2007;260(1-2):87-94.
Funchal, C., Tramontina, F., Quincozes dos Santos, A., Fraga de Souza, D., Gonçalves, C. A., Pessoa-Pureur, R., & Wajner, M. (2007). Effect of the branched-chain alpha-keto acids accumulating in maple syrup urine disease on S100B release from glial cells. Journal of the Neurological Sciences, 260(1-2), 87-94.
Funchal C, et al. Effect of the Branched-chain Alpha-keto Acids Accumulating in Maple Syrup Urine Disease On S100B Release From Glial Cells. J Neurol Sci. 2007 Sep 15;260(1-2):87-94. PubMed PMID: 17499767.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of the branched-chain alpha-keto acids accumulating in maple syrup urine disease on S100B release from glial cells. AU - Funchal,Cláudia, AU - Tramontina,Francine, AU - Quincozes dos Santos,André, AU - Fraga de Souza,Daniela, AU - Gonçalves,Carlos Alberto, AU - Pessoa-Pureur,Regina, AU - Wajner,Moacir, Y1 - 2007/05/17/ PY - 2007/01/15/received PY - 2007/03/06/revised PY - 2007/04/09/accepted PY - 2007/5/15/pubmed PY - 2007/12/7/medline PY - 2007/5/15/entrez SP - 87 EP - 94 JF - Journal of the neurological sciences JO - J Neurol Sci VL - 260 IS - 1-2 N2 - Accumulation of the branched-chain alpha-keto acids (BCKA), alpha-ketoisocaproic acid (KIC), alpha-keto-beta-methylvaleric acid (KMV) and alpha-ketoisovaleric acid (KIV) and their respective branched-chain alpha-amino acids (BCAA) occurs in tissues and biological fluids of patients affected by the neurometabolic disorder maple syrup urine disease (MSUD). The objective of this study was to verify the effect of the BCKA on S100B release from C6 glioma cells. The cells were exposed to 1, 5 or 10 mM BCKA for different periods and the S100B release was measured afterwards. The results indicated that KIC and KIV, but not KMV, significantly enhanced S100B liberation after 6 h of exposure. Furthermore, the stimulatory effect of the BCKA on S100B release was prevented by coincubation with the energetic substrate creatine and with the N-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase inhibitor, indicating that energy deficit and nitric oxide (NO) were probably involved in this effect. Furthermore, the increase of S100B release was prevented by preincubation with the protein kinase inhibitors KN-93 and H-89, indicating that KIC and KIV altered Ca2+/calmodulin (PKCaMII)- and cAMP (PKA)-dependent protein kinases activities, respectively. In contrast, other antioxidants such as glutathione (GSH) and trolox (soluble vitamin E) were not able to prevent KIC- and KIV-induced increase of S100B liberation, suggesting that the alteration of S100B release caused by the BCKA is not mediated by oxidation of sulfydryl or other essential groups of the enzyme as well as by lipid peroxyl radicals. Considering the importance of S100B for brain regulation, it is conceivable that enhanced liberation of this protein by increased levels of BCKA may contribute to the neurodegeneration characteristic of MSUD patients. SN - 0022-510X UR - https://www.unboundmedicine.com/medline/citation/17499767/Effect_of_the_branched_chain_alpha_keto_acids_accumulating_in_maple_syrup_urine_disease_on_S100B_release_from_glial_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-510X(07)00281-X DB - PRIME DP - Unbound Medicine ER -