Protective effect of taurine on hypochlorous acid toxicity to nuclear nucleoside triphosphatase in isolated nuclei from rat liver.
OBJECTIVE
Taurine has been shown to be an effective scavenger of hypochlorous acid (HOCl). The role of HOCl is well established in tissue damage associated with inflammation and injury. In the present study, the effect of HOCl on nuclear nucleoside triphosphatase of hepatocytes and the ability of taurine to prevent this effect were investigated.


METHODS
Isolated hepatic nuclei from rat liver were exposed to HOCl with or without taurine. The NTPase activity on nuclear envelope was assayed using ATP and GTP as substrates, respectively.


RESULTS
The first series of experiments evaluated the toxicity of HOCl and the efficacy of taurine to protect NTPase. HOCl at 10(-9)-5 x 10(-6) mol/L reduced nuclear NTPase activities in a concentration dependent manner (ATP and GTP as substrates) (P<0.01). HOCl at 10(-6) mol/L reduced the NTPase activity by 65% (ATP as substrate) and 76% (GTP as substrate). Taurine (10(-7) to 10(-4) mol/L) was tested for protection against HOCl at 10(-6) mol/L and the nuclei treated with 5 x 10(-4) mol/L taurine exhibited only 20% and 12% reduction in NTPase activities compared to untreated controls. A second study was performed comparing taurine to glutathione (GSH). GSH and HOCl at 10(-6) mol/L exhibited 46% and 67.4% reduction in NTPase activities compared with control. GSH (10(-4) mol/L) which was incubated with the nuclei and HOCl still exhibited 44.2% and 44.8% reduction in NTPase activities of untreated control. Taurine with HOCl only exhibited 15.2% and 17.1% reduction in NTPase activities, which provided more powerful protection against HOCl than GSH. The third experiment was undertaken to evaluate the specificity of taurine against HOCl. Incubation of rat hepatic nuclei with Fe(3+)/H(2)O(2) (1 m mol/L vs 5 micromol/L) resulted in a decrease in nuclear NTPase activities (P<0.01). When hepatic nuclei were incubated with Tau (10(-4) mol/L) and Fe(3+)/H(2)O(2) (1m mol/L vs 5 micromol/L), nuclear NTPase activities were only slightly increased as compared with that of incubation with Fe(3+)/H(2)O(2) alone. However, GSH failed to alter the NTPase activities induced by Fe(3+)/H(2)O(2).


CONCLUSIONS
The present findings indicate that HOCl can act as an inhibitor of nuclear NTPase. Taurine can antagonistically reduce the toxicity of HOCl to NTPase.
Li
Ju-Xiang
JX
Department of Biochemistry and Molecular Biology, Health Science Center, Peking University, Beijing 100083, China. lizaiquan@bjmu.edu.cn
Pang
Yong-Zheng
YZ
Tang
Chao-Shu
CS
Li
Zai-Quan
ZQ
D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D005978:Glutathione / Q000494:pharmacology; D006997:Hypochlorous Acid / Q000633:toxicity*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D043583:Nucleoside-Triphosphatase / Q000378:metabolism*; D016877:Oxidants / Q000633:toxicity*; D011755:Pyrophosphatases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000494:pharmacology*
D016877:Oxidants; D013654:Taurine; D006997:Hypochlorous Acid; D011755:Pyrophosphatases; D043583:Nucleoside-Triphosphatase; C021899:nucleotide pyrophosphatase; D005978:Glutathione