Studies on the action of porphyrinogenic trace metals on the activity of hepatic uroporphyrinogen decarboxylase

Woods, James S.; Kardish, R.; Fowler, Bruce A.

doi:10.1016/0006-291x(81)91688-0

Cited by 40 publications

(16 citation statements)

References 22 publications

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“…These results may reflect an in vivo thiol-dependent inhibition of URO-D, which would be in agreement with the inhibition of URO-D activity by As previously reported in vitro. 6 However, the decrease in URO-D activity observed in this study occurred in spite of the presence of DTT (an agent previously shown to restore the activity of the enzyme inhibited by arsenic in vitro6) in our reaction mixture, thus suggesting that thiol-independent mechanisms may also be involved. Finally, the significant depression of COPRO-O activity observed in kidney homogenates confirms previous findings in rats subchronically treated with sodium arsenate.5 A significant depression of hepatic COPRO-O activity was found when exposure to As III lasted more than 4 weeks.…”

Section: Discussionmentioning

confidence: 68%

“…1,5,6 For example, an increase in hepatic 5-aminolevulinate synthetase activity was found in rats treated with sodium arsenite through drinking water, 12 whereas other studies have shown that arsenic depresses renal coproporphyrinogen oxidase5 and ferrochelatasel activities in vivo and renal uroporphyrinogen decarboxylase activity in vitro. 6 However, the role played by these enzymic changes in the alterations of the urinary porphyrin profile has not yet been clarified.…”

Section: Introductionmentioning

confidence: 99%

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Time-dependent porphyric response in mice subchronically exposed to arsenic

Garcı́a-Vargas

Albores

et al. 1995

Hum Exp Toxicol

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1 A time-course study was carried out in mice subchroni cally exposed to As III (as sodium arsenite) or As V (as sodium arsenate), via drinking water, relating the pattern of urinary porphyrin excretion to the renal and hepatic enzyme activities of porphobilinogen deaminase (PBGD), uroporphyrinogen III synthetase (URO III-S), uropor phyrinogen decarboxylase (URO-D) and coproporphyrino gen oxidase (COPRO-O), as well as to the hepatic por phyrin accumulation in the treated animals. 2 A time-dependent, wave-like porphyric response was found in mice exposed to As V, and the increases seen in total urinary porphyrins (at 3 weeks of exposure) corre sponded to an increased activity of PBGD and Uro III-S in liver. 3 Significant decreases in renal URO-D and hepatic and renal COPRO-O activities were found in treated mice; these inhibitions were more pronounced in animals exposed to As III. 4 The combination of these enzymic effects may explain the time-dependent porphyric response of mice subchroni cally exposed to As. Finally, the relative magnitudes of URO-D and COPRO-O inhibitions may determine the pat tern of porphyrin concentration observed in urine and tis sues. 5 The decrease in renal URO-D activity may help to explain the inversion in the coproporphyrin/uroporphyrin ratio previously reported in humans chronically exposed to As; however, there were differences between the uri nary porphyrin profiles found in both species. The possi ble reasons for the similarities and differences are briefly discussed.

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Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Time-dependent porphyric response in mice subchronically exposed to arsenic

Garcı́a-Vargas

Albores

et al. 1995

Hum Exp Toxicol

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“…Hg 2+ complexed tightly with hydrosulphonyl moieties after entering the body, causing depletion of intracellular hydrosulphonyl moieties and release of reactive oxygen free radicals. It resulted, either indirectly or directly, in oxidative stress and lipid peroxidation37. However, luteolin attenuates oxidative stress and free radical damage, and enhances the antioxidant system including superoxide dismutase (SOD) and GSH, indicating that luteolin provides protection against HgCl 2 -induced lipid peroxidation and oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Sirt1/Nrf2/TNF-α signaling pathway by luteolin is critical to attenuate acute mercuric chloride exposure induced hepatotoxicity

Yang

Xiao

et al. 2016

Sci Rep

142

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Inorganic mercury, though a key component of pediatric vaccines, is an environmental toxicant threatening human health via accumulating oxidative stress in part. Luteolin has been of great interest because of its antiinflammatory, anticarcinogenic and antioxidative effects. Here we hypothesized that luteolin would attenuate hepatotoxicity induced by acute inorganic mercury exposure. Kunming mice were treated with luteolin (100 mg/kg) 24 h after administration of 4 mg/kg mercuric chloride (HgCl2). The results showed that luteolin ameliorated HgCl2 induced anemia and hepatotoxicity, regulating radical oxygen species (ROS) production and hepatocyte viability in vitro and oxidative stress and apoptosis in vivo. Furthermore, luteolin reversed the changes in levels of inflammation- and apoptosis-related proteins involving NF-κB, TNF-α, Sirt1, mTOR, Bax, p53, and Bcl-2, and inhibited p38 MAPK activation. Luteolin enhanced antioxidant defense system based on Keap1, Nrf2, HO-1, NQO1, and KLF9. Moreover, luteolin did not affect miRNA-146a expression. Collectively, our findings, for the first time, elucidate a precise mechanism for attenuation of HgCl2-induced liver dysfunction by dietary luteolin via regulating Sirt1/Nrf2/TNF-α signaling pathway, and provide a foundation for further study of luteolin as a novel therapeutic agent against inorganic mercury poisoning.

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“…The uroporphyrinogen decarboxylase from human sources is inhibited by a wide variety of sulphydryl reagents (de Verneuil et al, 1983a;Elder et al, 1983) and by heavy metals (Kushner et al, 1972;Woods et al, 1981). This has been interpreted as is 4.4.…”

Section: Introductionmentioning

confidence: 97%

Purification and properties of the uroporphyrinogen decarboxylase from Rhodobacter sphaeroides

Jones

Jordan

1993

Biochemical Journal

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Uroporphyrinogen decarboxylase (EC 4.1.1.37) was purified 600-fold from Rhodobacter sphaeroides grown anaerobically in the light. The enzyme, under both denaturing and non-denaturing conditions, is a monomer of M(r) 41,000. The Km values are 1.8 microM and 6.0 microM for the conversion of uroporphyrinogen I and III to coproporphyrinogen I and III respectively. The enzyme is susceptible to inhibition by both uroporphyrinogen and uroporphyrin. The pH optimum is 6.8 and the isoelectric point is 4.4. The importance of cysteine and arginine residues is implicated from studies with inhibitors. The sequence of the first 29 amino acids of the N-terminus shows a high degree of similarity to the primary structures of other uroporphyrinogen decarboxylases. Studies on the order of decarboxylation of the four acetic acid side chains of uroporphyrinogen III suggest that at high substrate levels a random route is preferred.

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Studies on the action of porphyrinogenic trace metals on the activity of hepatic uroporphyrinogen decarboxylase

Cited by 40 publications

References 22 publications

Time-dependent porphyric response in mice subchronically exposed to arsenic

Time-dependent porphyric response in mice subchronically exposed to arsenic

Regulation of Sirt1/Nrf2/TNF-α signaling pathway by luteolin is critical to attenuate acute mercuric chloride exposure induced hepatotoxicity

Purification and properties of the uroporphyrinogen decarboxylase from Rhodobacter sphaeroides

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