Differential Expression of Carnosine, Homocarnosine and N-Acetyl-L-Histidine Hydrolytic Activities in Cultured Rat Macroglial Cells

Abstract

N-acetyl-L-histidine (NAH) and N-acetyl-L-aspartate (NAA) are representatives of two series of substances that are synthesized by neurons and other cells in the vertebrate central nervous system (CNS). Histidine containing homologs of NAH are beta-alanyl-L-histidine or carnosine (Carn) and gamma-aminobutyrl-L-histidine or homocarnosine (Hcarn). A homolog of NAA is N-acetylaspartylglutamate (NAAG). These substances belong to a unique group of osmolytes in that they are synthesized in cells that may not to be able to hydrolyze them, and are released in a regulated fashion to a second compartment where they can be rapidly hydrolyzed. In this investigation, the catabolic activities for NAH, Carn, and Hcarn in cultured macroglial cells and neurons have been measured, and the second compartment for NAH and Hcarn has been identified only with astrocytes. In addition, oligodendrocytes can only hydrolyze Carn, although Carn can also be hydrolyzed by astrocytes. Thus, astrocytes express hydrolytic activity against all three substrates, but oligodendrocytes can only act on Carn. The cellular separation of these hydrolytic enzyme activities, and the possible nature of the enzymes involved are discussed.

Canavan disease, a rare early-onset human spongiform leukodystrophy: Insights into its genesis and possible clinical interventions

“…Whereas ASPA showed no activity against NAH, amidohydrolase I was active against NAA at 0.15 mmol/ g/h or about 6% of its activity against NAH. These two enzymes are associated with different glial cells in rat brain cell cultures, with ASPA highly expressed in oligodendrocytes and amidohydrolase I activity highly expressed in astrocytes [30]. NAH has previously been found to be present in rat brain [31], and in this investigation it was found that of all cells tested, only cultured rat neurons contained small quantities of NAH.…”

“…In CD, excretion of NAA by this alternate method ranges from 3 to 5 mmol/d, a value that represents the turnover of almost all brain synthesized NAA each day [8]. Another minor pathway for removal of some NAA from brain ECF in CD could be via astrocyte uptake and hydrolysis by amidohydrolase I [30]. In this article, except where specific metabolic sequences are involved, the terms NAA and its NAA-waterMe þ complex are used interchangeably since the anionic solute NAA cannot exist independently at the physiological pH of the brain.…”

N-acetyl-l-histidine, a Prominent Biomolecule in Brain and Eye of Poikilothermic Vertebrates

“…In the dietary His supplementation studies [ 19 , 20 ], a therapeutic role for the essential amino acid His in synthesis of NAH and preventing lens cataract formation in teleost fish was reported. This observation may have relevance to homeotherms where NAH and the His dipeptides, Carn and Hcarn are present in cultured rat neurons [ 26 ] and Carn and Hcarn are important biomolecules in human brain and eye.…”

Carnosine as a Possible Drug for Zinc-Induced Neurotoxicity and Vascular Dementia

“…These results are consistent with previous studies. In the mammalian brain, carnosine and homocarnosine, but not anserine, have been detected [96]. It is secreted from oligodendrocytes by the stimulation of glutamate [97].…”