Histidine Decarboxylase Articles 2

© 2012

Differential activity of histidine decarboxylase in normal and pre-eclamptic placentae

            (Brew, Lakasing et al. 2007) Download

Histamine and histidine decarboxylase up-regulation in colorectal cancer correlation with tumor stage

            (Masini, Fabbroni et al. 2005) Download

Upregulation of histidine decarboxylase expression in superficial cortical nephrons during pregnancy in mice and women

            (Morgan, Montgomery et al. 2006) Download

Mechanisms regulating pregnancy-induced changes in renal function are incompletely understood. Few candidate genes have been identified and data suggest that alternate mechanisms remain to be elucidated. Our objective was to screen thousands of genes expressed in kidneys from mice throughout gestation to identify possible key regulators of renal function during pregnancy. Mouse complementary DNA microarrays were used to screen for differences in expression during pregnancy in C57BL/6 mice. Interesting candidate genes whose expression varied with pregnancy were further analyzed by reverse transcription-PCR and Northern blot. Expression was localized by in situ hybridization and immunohistochemistry. Follow-up immunohistochemical analyses in archival human kidney sections from the fetus, non-pregnant, and pregnant women were also performed. Histidine decarboxylase (HDC), the enzyme that synthesizes histamine, was markedly upregulated in the mouse kidney during pregnancy. HDC expression localized to proximal tubule cells of fetal and adult mice. Females showed strong expression in the juxtamedullary zone before pregnancy and upregulation in the superficial cortical zone (SCZ) by mid-gestation. Histamine colocalized with HDC. Male mice showed only low HDC expression. Similar expression patterns were observed in human kidneys. Our results show that HDC expression and histamine production are increased in the SCZ during pregnancy. If histamine acts as a vasodilator, we speculate that increasing production in the SCZ may increase renal blood flow to this zone and recruit superficial cortical nephrons during pregnancy.


Carnosine protects against permanent cerebral ischemia in histidine decarboxylase knockout mice by reducing glutamate excitotoxicity

            (Shen, He et al. 2010) Download

Recently, we showed that carnosine protects against NMDA-induced excitotoxicity in differentiated PC12 cells through a histaminergic pathway. However, whether the protective effect of the carnosine metabolic pathway also occurs in ischemic brain is unknown. Utilizing the model of permanent middle cerebral artery occlusion (pMCAO) in mice, we found that carnosine significantly improved neurological function and decreased infarct size in both histidine decarboxylase knockout and the corresponding wild-type mice to the same extent. Carnosine decreased the glutamate levels and preserved the expression of glutamate transporter-1 (GLT-1) but not the glutamate/aspartate transporter in astrocytes exposed to ischemia in vivo and in vitro. It suppressed the dissipation of Delta Psi(m) and generation of mitochondrial reactive oxygen species (ROS) induced by oxygen-glucose deprivation in astrocytes. Furthermore, carnosine also decreased the mitochondrial ROS and reversed the decrease in GLT-1 induced by rotenone. These findings are the first to demonstrate that the mechanism of carnosine action in pMCAO may not be mediated by the histaminergic pathway, but by reducing glutamate excitotoxicity through the effective regulation of the expression of GLT-1 in astrocytes due to improved mitochondrial function. Thus, our study reveals a novel antiexcitotoxic agent in ischemic injury.


References

Brew, O., L. Lakasing, et al. (2007). "Differential activity of histidine decarboxylase in normal and pre-eclamptic placentae." Placenta 28(5-6): 585-7.

Masini, E., V. Fabbroni, et al. (2005). "Histamine and histidine decarboxylase up-regulation in colorectal cancer: correlation with tumor stage." Inflamm Res 54 Suppl 1: S80-1.

Morgan, T. K., K. Montgomery, et al. (2006). "Upregulation of histidine decarboxylase expression in superficial cortical nephrons during pregnancy in mice and women." Kidney Int 70(2): 306-14.

Shen, Y., P. He, et al. (2010). "Carnosine protects against permanent cerebral ischemia in histidine decarboxylase knockout mice by reducing glutamate excitotoxicity." Free Radic Biol Med 48(5): 727-35.