Limits...
Aldehyde dehydrogenase-independent bioactivation of nitroglycerin in porcine and bovine blood vessels.

Neubauer R, Wölkart G, Opelt M, Schwarzenegger C, Hofinger M, Neubauer A, Kollau A, Schmidt K, Schrammel A, Mayer B - Biochem. Pharmacol. (2015)

Bottom Line: ALDH2 mRNA expression and the rates of GTN denitration were similarly low, excluding a significant contribution of ALDH2 to the bioactivation of GTN in these vessels.Attempts to identify the responsible pathway with enzyme inhibitors did not provide conclusive evidence for the involvement of ALDH3A1, cytochrome P450, or GSH-S-transferase.If present in the human vasculature, this pathway might contribute to the therapeutic effects of organic nitrates that are not metabolized by ALDH2.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, Karl-Franzens-Universität Graz, Austria.

Show MeSH

Related in: MedlinePlus

Relative mRNA expression of ALDH isoforms in rat aorta, and porcine and bovine coronary arteries. Total RNA was isolated from rat aortas (n = 5), and bovine and porcine coronary arteries (n = 5–6). mRNA levels were determined by SYBR Green-based qPCR, and expression levels are calculated relative to the ALDH2 mRNA levels of rat aortas after normalization to cyclophilin A. Data are mean values ± SEM of 5–6 experiments.; n.d., not detectable (<0.0001%). ALDH1A1 mRNA was not determined in PCA. *p < 0.05 compared with ALDH2 in rat aorta; #p < 0.05 compared with ALDH1A1 in rat aorta.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4321882&req=5

fig0025: Relative mRNA expression of ALDH isoforms in rat aorta, and porcine and bovine coronary arteries. Total RNA was isolated from rat aortas (n = 5), and bovine and porcine coronary arteries (n = 5–6). mRNA levels were determined by SYBR Green-based qPCR, and expression levels are calculated relative to the ALDH2 mRNA levels of rat aortas after normalization to cyclophilin A. Data are mean values ± SEM of 5–6 experiments.; n.d., not detectable (<0.0001%). ALDH1A1 mRNA was not determined in PCA. *p < 0.05 compared with ALDH2 in rat aorta; #p < 0.05 compared with ALDH1A1 in rat aorta.

Mentions: To see whether low ALDH2 expression is a peculiarity of coronary arteries, we measured the protein levels in several types of porcine blood vessels and compared the data with the ALDH2 expression levels in rat liver, rat aorta, and porcine liver. As shown in Fig. 4E, the highest expression levels were found in liver, containing about 150 (rat) and 40 (pig) ng/mg wet weight. Rat aorta expressed about 40 ng of ALDH2 per mg tissue, whereas expression levels were below 5 ng/mg in all porcine arteries studied (coronary, liver, renal, and splenic artery). The data on protein levels agreed well with ALDH2 mRNA expression (Fig. 5), which was hardly detectable in porcine coronary arteries (∼0.01% of rat aorta) and about 18% of rat aortic levels in bovine coronary arteries. Expression levels of ALDH1A1 and ALDH3A1, respectively, were about 0.05 and 3% of the ALDH2 levels in rat aorta, and not or hardly detectable in porcine and bovine coronary arteries.


Aldehyde dehydrogenase-independent bioactivation of nitroglycerin in porcine and bovine blood vessels.

Neubauer R, Wölkart G, Opelt M, Schwarzenegger C, Hofinger M, Neubauer A, Kollau A, Schmidt K, Schrammel A, Mayer B - Biochem. Pharmacol. (2015)

Relative mRNA expression of ALDH isoforms in rat aorta, and porcine and bovine coronary arteries. Total RNA was isolated from rat aortas (n = 5), and bovine and porcine coronary arteries (n = 5–6). mRNA levels were determined by SYBR Green-based qPCR, and expression levels are calculated relative to the ALDH2 mRNA levels of rat aortas after normalization to cyclophilin A. Data are mean values ± SEM of 5–6 experiments.; n.d., not detectable (<0.0001%). ALDH1A1 mRNA was not determined in PCA. *p < 0.05 compared with ALDH2 in rat aorta; #p < 0.05 compared with ALDH1A1 in rat aorta.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4321882&req=5

fig0025: Relative mRNA expression of ALDH isoforms in rat aorta, and porcine and bovine coronary arteries. Total RNA was isolated from rat aortas (n = 5), and bovine and porcine coronary arteries (n = 5–6). mRNA levels were determined by SYBR Green-based qPCR, and expression levels are calculated relative to the ALDH2 mRNA levels of rat aortas after normalization to cyclophilin A. Data are mean values ± SEM of 5–6 experiments.; n.d., not detectable (<0.0001%). ALDH1A1 mRNA was not determined in PCA. *p < 0.05 compared with ALDH2 in rat aorta; #p < 0.05 compared with ALDH1A1 in rat aorta.
Mentions: To see whether low ALDH2 expression is a peculiarity of coronary arteries, we measured the protein levels in several types of porcine blood vessels and compared the data with the ALDH2 expression levels in rat liver, rat aorta, and porcine liver. As shown in Fig. 4E, the highest expression levels were found in liver, containing about 150 (rat) and 40 (pig) ng/mg wet weight. Rat aorta expressed about 40 ng of ALDH2 per mg tissue, whereas expression levels were below 5 ng/mg in all porcine arteries studied (coronary, liver, renal, and splenic artery). The data on protein levels agreed well with ALDH2 mRNA expression (Fig. 5), which was hardly detectable in porcine coronary arteries (∼0.01% of rat aorta) and about 18% of rat aortic levels in bovine coronary arteries. Expression levels of ALDH1A1 and ALDH3A1, respectively, were about 0.05 and 3% of the ALDH2 levels in rat aorta, and not or hardly detectable in porcine and bovine coronary arteries.

Bottom Line: ALDH2 mRNA expression and the rates of GTN denitration were similarly low, excluding a significant contribution of ALDH2 to the bioactivation of GTN in these vessels.Attempts to identify the responsible pathway with enzyme inhibitors did not provide conclusive evidence for the involvement of ALDH3A1, cytochrome P450, or GSH-S-transferase.If present in the human vasculature, this pathway might contribute to the therapeutic effects of organic nitrates that are not metabolized by ALDH2.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, Karl-Franzens-Universität Graz, Austria.

Show MeSH
Related in: MedlinePlus