生物活性 | |||
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描述 | Mitochondrial aldehyde dehydrogenase (ALDH2) plays roles in either toxic environmental aldehydes or organic ethanol metabolism as well as in disease therapy like cardiovascular disease. Alda-1 is an agonist that activates both wild-type ALDH2 and ALDH2*2 by bounding to the apo-form of them at the exit of the substrate tunnel and extends in toward the active site. At pH 7.5, the length and nature of 100 μM aldehydes that were acetaldehyde, propionaldehyde and butyraldehyde were activated in dependent ways with the concentrations of Alda-1 of 0, 3, 6, 20, 30 μM respectively. Alda-1 also antagonized daidzin inhibition of both ALDH2 and ALDH2*2 in a dependent way with concentrations of 10 μM. Furthermore, the combined activatory could significantly increase the effects of both Alda-1 and NAD+ on ester hydrolysis for the two enzymes, which inversely became antagonistic for ALDH2 if the concentration is very high[1]. In male sprague-dawley rats study model with lung ischemia/reperfusion (I/R) injuries, 10 mg/kg Alda-1 treatment could significantly alleviate the I/R injury. The hepatic I/R could increase ROC which was reduced by Alda-1 treatment and damage ALDH2 activity without changing ALDH2 expression and the ALDH2 activity could also be increased by Alda-1. The accumulation of MDA and 4-HNE due to I/R could also be inhibited, indicating that Alda-1 could activate ALDH2 activity and thus diminish the accumulation of toxic products. Furthermore, Alda-1 was proved to reduce the inflammatory response, ROS level, cell viability and mitochondrial membrane potential[2]. In sum, Alda-1 could enhance the catalytic ALDH2 activity by 2-times with EC50 of 20 μM and inhibit 4-HNE-induced inactivation of ALDH2. 8 mg/kg Injection of Alda-1 could decrease creatine kinase release into the blood by 50%[3]. |
实验方案 | |||
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1mg | 5mg | 10mg | |
1 mM 5 mM 10 mM |
3.08mL 0.62mL 0.31mL |
15.42mL 3.08mL 1.54mL |
30.85mL 6.17mL 3.08mL |
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