Upregulation of N-acetylaspartic acid alters inflammation, transcription and contractile associated protein levels in the stomach and smooth muscle contractility.
N-acetylaspartic acid (NAA) is converted into aspartate and acetate by aspartoacylase. Abnormal levels of the enzyme leads to accumulation of NAA and these changes have been observed in Canavan disease and type 2 diabetes. How upregulation of NAA affect the gastrointestine protein levels and the function is not known. Incubation of rat stomach tissue with NAA 1.5 mM, 1.5 microM and 1.5 nM induced inflammatory agents TNFalpha, p38MAPK, iNOS, PKC, COX2 and ICAM3; transcription factors phospho-NF-kBp65, cjun and cfos; contractile proteins MLCK and phospho MLC; and calcium channel alpha1C and calcium channel, voltage-dependent, beta 3 subunit compared to their respective control. Incubation of circular smooth muscle cells with the above doses of NAA induced contractility compared to the control. These studies suggest that NAA alters proteins levels and smooth muscle contractility and these changes likely to contribute to gastrointestinal disorder seen in these diseases.
Surendran
Sankar
S
Department of Pediatrics, University of Texas Health Science Center, Houston, TX 77030, USA. surendran.sankar@uth.tmc.edu
D000704:Analysis of Variance; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D003285:Contractile Proteins / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D020869:Gene Expression Profiling; D007249:Inflammation / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism*; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D003285:Contractile Proteins; D047908:Intracellular Signaling Peptides and Proteins; D014157:Transcription Factors; D001224:Aspartic Acid; C000179:N-acetylaspartate; D048051:p38 Mitogen-Activated Protein Kinases