Disease relevance of Ddah1

• To study the effect of dimethylarginine dimethylaminohydrolase on tumour growth and vascular development, the rat C6 glioma cell line was manipulated to overexpress the rat gene for dimethylarginine dimethylaminohydrolase I [1].
• Overexpression of dimethylarginine dimethylaminohydrolase enhances tumor hypoxia: an insight into the relationship of hypoxia and angiogenesis in vivo [2].
• In situ hybridization analysis revealed characteristic DDAH1 mRNA expression in the embryonic spinal cord, which was especially strong in the ventral horn and dorsal root ganglion (DRG) [3].
• With pulmonary hypertension, no changes in DDAHI expression were observed, but DDAHII expression was markedly decreased compared with age-matched controls [4].

Psychiatry related information on Ddah1

• The preservation of DDAH activity and the reduction of ADMA accumulation in neurons may be a new strategy for the treatment of Alzheimer's disease and cognitive impairment in normal aging [5].

High impact information on Ddah1

• Dimethylargininase metabolizes ADMA to L-citrulline and plays a key role in determining the in vivo levels of ADMA [6].
• RESULTS: Compared with HS rats, there was a significant (P < 0.05) increase in LS rats of nNOS protein in kidney and immunohistochemical expression in the macula densa, and of eNOS protein expression and immunohistochemical expression in the microvascular endothelium, and of DDAH protein expression [7].
• Losartan prevented these effects of salt on the expression of eNOS or DDAH, both of which were also increased by Ang II infusions in HS rats [7].
• Renal expression of constitutive NOS and DDAH: separate effects of salt intake and angiotensin [7].
• In conclusion, sites of DDAH expression in the vasculature or nephron are all sites of expression of an isoform of NOS [8].

Biological context of Ddah1

• Since the L-arginine:(L-NMA + ADMA) ratio determines NO synthase (NOS) activity, we compared the immunohistochemical distribution of NOS with NG, NG-dimethylarginine dimethylaminohydrolase (DDAH), which inactivates dimethylarginines (DMA) and L-NMA by hydrolysis to L-citrulline [8].
• The profile of DDAH mRNA up-regulation in the injured hypoglossal motor neurons paralleled that of NADPH diaphorase staining [9].
• The interaction of DDAH was mainly directed to the C-terminal domain (CTD) and to the cysteine/serine-rich domain (CSRD) of neurofibromin, coinciding with the regions containing specific PKA phosphorylation sites [10].
• The protective effect of PDTC suggests that L-homocysteine inactivates DDAH in neurons by reacting with the cysteine residue in its active site [5].
• In summary, the present results suggest that DMB protects endothelial damage induced by LPC in vitro and LDL in vivo or in endothelial cells, and the protective effect of DMB on the endothelium is related to reduction of ADMA concentration via an increase of DDAH activity by inhibition of lipid peroxidation [11].

Anatomical context of Ddah1

• This data demonstrates that dimethylarginine dimethylaminohydrolase plays a pivotal role in tumour growth and the development of the tumour vasculature by regulating the concentration of nitric oxide and altering vascular endothelial cell growth factor production [1].
• DDAH1 was also detected in the brain, kidney, digestive tract, and in other tissues [3].
• Immunostaining for DDAH was present in PT, TAL, MD, and IC, and was also present in the glomerulus, Bowman's capsule, and endothelium of blood vessels [8].
• Therefore, DDAH may regulate the cellular L-arginine: methylarginine levels in specific renal cells, thereby governing cell-specific L-arginine uptake and NO generation in renal tubular epithelium [8].
• Incubation of lysed red blood cell (RBC) supernatant yielded a significant decrease in ADMA that was blocked by 4124W, a synthetic inhibitor of dimethylarginine dimethylaminohydrolase, the only reported enzyme to hydrolyze ADMA [12].

Associations of Ddah1 with chemical compounds

• Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is an enzyme that metabolizes methylated arginine to citrulline and methylamine, thus working to produce nitric oxide (NO) [3].
• CONCLUSION: The expressions of eNOS in cortical microvascular endothelium and DDAH in kidney are enhanced by Ang II acting on AT(1) receptors [7].
• It is concluded that L-homocysteine inhibits DDAH activity, thereby causing ADMA accumulation and decreasing nitric oxide production in cultured neurons [5].
• The addition of PDTC caused a dose-dependent increase in DDAH activity [5].
• In this study, we identified a cellular neurofibromin-associating protein, N(G),N(G)-dimethylarginine dimethylaminohydrolase (DDAH) that is known as a cellular NO/NOS regulator [10].

Other interactions of Ddah1

• Evidence for dysregulation of dimethylarginine dimethylaminohydrolase I in chronic hypoxia-induced pulmonary hypertension [13].

Analytical, diagnostic and therapeutic context of Ddah1

• DDAH was detected in small vesicles of TAL and PT by electron microscopic (EM) immunocytochemistry [8].
• The present study demonstrated that both DDAH and nNOS mRNAs are up-regulated after axotomy in injured hypoglossal motor neurons [9].
• Tissue DDAH expression was examined by real-time polymerase chain reaction (PCR), immunoblotting, and immunohistochemistry [14].
• METHODS AND RESULTS: Using Western blotting, we showed that DDAHI expression did not change in the normal developing lung; however, DDAHII increased after birth and reached a peak at 1 day [4].

References