The effects of lanthanoid on the structure–function of lactate dehydrogenase from mice heart.
The activity of lactate dehydrogenase (LDH, EC1.1.1.27) is often changed upon inflammatory responses in animals. Lanthanoid (Ln) was shown to provoke various inflammatory responses both in rats and mice; however, the molecular mechanism by which Ln3+ exert its toxicity has not been completely understood, especially that we know little about the mechanism of the interaction between Ln with 4f electron shell and alternation valence and LDH. In this report, we investigated the mechanisms of LaCl3, CeCl3, and NdCl3 on LDH activity in vivo and in vitro. Our results showed that La3+, Ce3+, and Nd3+ could significantly activate LDH in vivo and in vitro; the order of activation was Ce3+>Nd3+> La3+>control. The affinity of LDH for Ce3+ was higher than Nd3+ and La3+; the saturated binding sites for Ce3+ on the LDH protein were 1.2 and for La3+ and Nd3+ 1.55. Ln3+ caused the reduction of exposure degree of cysteine or tryptophan/tyrosine of LDH, the increase of space resistance, and the enhancement of α-helix in secondary structure of LDH, which was greatest in Ce3+ treatment, medium in Nd3+ treatment, and least in La3+ treatment. It implied that the changes of structure-function on LDH caused by Ln3+ were closely related to the characteristics of 4f electron shell and alternation valence in Ln.
Li
Na
N
Medical College of Soochow University, Suzhou 215123, People's Republic of China.
Duan
Yanmei
Y
Zhou
Min
M
Liu
Chao
C
Hong
Fashui
F
D000818:Animals; D002563:Cerium / Q000494:pharmacology; D002942:Circular Dichroism; D004789:Enzyme Activation / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism*; D028581:Lanthanoid Series Elements / Q000494:pharmacology*; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D051379:Mice; D009206:Myocardium / Q000201:enzymology*; D009354:Neodymium / Q000494:pharmacology
D028581:Lanthanoid Series Elements; C028521:lanthanum chloride; C053739:neodymium chloride; D009354:Neodymium; D002563:Cerium; D007811:Lanthanum; D007770:L-Lactate Dehydrogenase; C026690:cerous chloride