Disease relevance of Cpe

• Ibotenic acid lesions of the hippocampus eliminated the majority of the label, which had been present over pyramidal cells, though labeling was increased over areas of reactive gliosis, suggesting that activated astrocytes can also synthesize CPE mRNA [1].
• Altered expression of the neuropeptide-processing enzyme carboxypeptidase E in the rat brain after global ischemia [2].
• The intracellular distribution and molecular heterogeneity of carboxypeptidase H was studied in rat insulinoma tissue and isolated islets of Langerhans by a combination of immunohistochemical, ultrastructural, subcellular fractionation, and immunoblotting analyses [3].
• Regulation of carboxypeptidase E by membrane depolarization in PC12 pheochromocytoma cells: comparison with mRNAs encoding other peptide- and catecholamine-biosynthetic enzymes [4].
• CPE mRNA is also influenced by the insulin shock, with levels increasing to 155% of the control level after 6 h and 170% after 2 days [5].

Psychiatry related information on Cpe

• CONCLUSION: The abilities of CPH to attenuate memory deficits and neuronal damage after ischemia may be beneficial in cerebrovascular type dementia [6].

High impact information on Cpe

• Enkephalin convertase, an enkephalin-forming carboxypeptidase, is potently inhibited by guanidinoethylmercaptosuccinic acid (GEMSA) [7].
• These interactions were demonstrated by the behavior of promoters that contained either linker-scanning or deletion mutations of the UPE in combination with point mutations of the CPE (bidomain mutants) [8].
• Both in situ hybridization and indirect immunofluorescence studies indicate that CPE is expressed in photoreceptors in the dark [9].
• During light onset, CPE expression is rapidly induced in retinal ganglion cells, whereas expression in photoreceptors is reduced [9].
• Immunoreactivity to CPE in the hippocampus is found in the pyramidal cells and in the inner part of the molecular layer of the dentate gyrus [10].

Chemical compound and disease context of Cpe

• Decreased expression of carboxypeptidase E protein is correlated to estrogen-induction of rat pituitary tumors [11].
• Synaptic parameters of the cerebellar glomerulus were calculated and compared with similar data obtained from old Wistar rats of the same breed treated with centrophenoxine (CPH; HelferginR, Promonta, Hamburg) in the form of intraperitoneal injections (100 mg/kg body weight) for 40 days [12].

Biological context of Cpe

• A 2.2-kilobase pair cDNA was shown to contain the complete amino acid sequence of rat carboxypeptidase H [13].
• Nuclease protection analysis shows that alternative splicing of exons 7, 8, and 9 does not occur, indicating that the heterogeneity of the C-terminal region of CPE is due to posttranslational processing [14].
• These animals have a point mutation in carboxypeptidase E (CPE), an exopeptidase that removes C-terminal basic amino acids from peptide intermediates [15].
• Together, these findings show that CPE is a key enzyme for pro-GnRH processing in vivo; however, the reproductive deficits in Cpe(fat/fat) males appear to be due primarily to abnormal sexual behavior [15].
• Regions of the CPE gene spanning the major transcription initiation site (-12 to 47) are sufficient for low levels of transcription [16].

Anatomical context of Cpe

• No carboxypeptidase H mRNA was detected in rat liver, spleen, kidney, lung, and mammary gland [13].
• High levels of CPE mRNA are present in rat hypothalamus, hippocampus, midbrain, striatum, and cerebral cortex; and moderate levels are present in the brain stem, cerebellum, heart, adrenal, and eye [17].
• Carboxypeptidase-H is a molecule expressed within islet secretory granules and neurendocrine cells [18].
• Northern blot analyses reveal that prohormone convertase 2 (PC2), carboxypeptidase E, glutaminyl cyclase, and peptidyl-glycine alpha-amidating monooxygenase are expressed in the GT1 cells and rat hypothalamus [19].
• Carboxypeptidase E in rat antropyloric mucosa: distribution in progenitor and mature endocrine cell types [20].

Associations of Cpe with chemical compounds

• Treatment of AtT20 cells with dexamethasone decreased the levels of both carboxypeptidase H and preproopiomelanocortin (POMC) mRNAs by approximately 30% [13].
• These data indicate that immature G/D cells are able to process gastrin to glycine-extended forms and that CPE-mediated processing is not a characteristic of mature somatostatin and serotonin cells [20].
• Selective destruction of CA 3-4 pyramidal cells with kainic acid eliminates EC in the pyramidal cell region [21].
• Ibotenic acid lesions of the caudate nucleus destroy binding in the substantia nigra pars reticulata ipsilateral to the lesion, suggesting that nigral EC is associated with axons originating in the caudate nucleus [21].
• Pituitary-specific transcriptional initiation sites of the rat carboxypeptidase-H gene and the influence of thyroid hormone status [22].

Other interactions of Cpe

• Only one of the exon/intron junctions of the rat CPE gene is present in a comparable position within the genes for carboxypeptidase-A and -B, both of which are only 17-21% homologous to CPE at the amino acid level [14].
• We investigated the biosynthesis of various constituents (chromogranins A and B, secretogranin II, carboxypeptidase H and synaptin/synaptophysin) of large dense core and small vesicles in PC12 cells [23].
• Northern blot analysis indicates that BRL-3A cells express carboxypeptidase E mRNA in addition to mRNA encoding furin, a prohormone-processing endopeptidase [24].
• Comparison of the regulation of carboxypeptidase E and prolactin in GH4C1 cells, a rat pituitary cell line [25].
• Proteolytic processing of chromogranin A in purified insulin granules. Formation of a 20 kDa N-terminal fragment (betagranin) by the concerted action of a Ca2+-dependent endopeptidase and carboxypeptidase H (EC 3.4.17.10) [26].

Analytical, diagnostic and therapeutic context of Cpe

• Northern blot analysis identified a single carboxypeptidase H mRNA of approximately 2.3 kilobases in brain, pituitary, and heart, as well as in mouse AtT20 cells [13].
• Isolation and sequence analysis of cDNA for rat carboxypeptidase E [EC 3.4.17.10], a neuropeptide processing enzyme [17].
• Enkephalin convertase localization by [3H]guanidinoethylmercaptosuccinic acid autoradiography: selective association with enkephalin-containing neurons [7].
• Using in situ hybridization with 35S-labeled oligonucleotide probes, we have mapped the localization of CPE mRNA in the rat brain [1].
• After extended reperfusion (24 to 72 hours), both carboxypeptidase E messenger RNA and protein levels were decreased [2].

References