Disease relevance of PENK

• Proenkephalin antigenic domains, mapped using phage display libraries and synthetic peptides, are differentially revealed in the three distribution patterns [1].
• These results demonstrate that functional Kex2-related endoproteases are expressed in human pheochromocytomas and may be involved in the processing of proenkephalin [2].
• Therefore, it has been suggested that an enhanced striatal PENK mRNA expression may reflect to some extent an increase in the activity of the GABAergic striatopallidal pathway whose overactivity has been suggested to take place in the course of Parkinson's disease [3].
• Gene expression analysis showed that PENK expression was down-regulated in prostate cancer [4].
• Normal epithelial cells of human endometrium, and Ishikawa human endometrial adenocarcinoma cells (an in vitro model for the study of steroid hormone effects on human endometrium) have been found to express and secrete opioid peptides deriving from proenkephalin, prodynorphin, and proopiomelanocortin [5].

Psychiatry related information on PENK

• Association and linkage studies of CRH and PENK genes in bipolar disorder: a collaborative IGSLI study [6].
• We tested the hypothesis that the alleles at the (CA)n repeat of the proenkephalin gene (PENK) might be associated with opioid addiction in 31 non-Hispanic Caucasian subjects with opioid dependence (heroin), 89 ethnically matched subjects with substance dependence other than opioid dependence and 132 controls [7].
• Opioid peptides in Huntington's disease: alterations in prodynorphin and proenkephalin system [8].
• Striking dynamic alterations include a pronounced increase in levels of proenkephalin mRNA in the corpus striatum after blockade of dopamine receptors, but changes in opioid peptide mRNA after opiate addiction are less clear [9].
• A cross-validation of the Keane and Penk MMPI scales as measures of post-traumatic stress disorder [10].

High impact information on PENK

• The DNA sequences required for regulation by both cAMP and phorbol ester map to the same 37-base pair (bp) region located 107-71 bp 5' to the mRNA cap site of the proenkephalin gene [11].
• Proenkephalin messenger RNA levels are regulated in response to cAMP analogues, activators of adenylate cyclase, nicotinic agonists and depolarization, suggesting that expression of the gene encoding proenkephalin is regulated by trans-synaptic events involving cell-surface-receptor activation [11].
• The human proenkephalin gene consists of four exons, of which the main exon (exon IV) contains all known biologically active peptides--six Met-enkephalin sequences and one Leu-enkephalin sequence [12].
• Polymorphism and absence of Leu-enkephalin sequences in proenkephalin genes in Xenopus laevis [12].
• We report here the primary structures of the putative main exons of two proenkephalin genes in X. laevis, each of which codes for seven Met-enkephalin sequences but no Leu-enkephalin, indicating that Met-enkephalin preceded Leu-enkephalin in the evolution of the proenkephalin gene [12].

Chemical compound and disease context of PENK

• Elevated brain pH was observed in heroin overdose with positive alcohol toxicity suggesting potentiated alcohol-induced rapidity of heroin deaths. mRNA expression levels of the dopamine-related genes and proenkephalin were positively correlated with brain pH [13].
• Different AP-1 or cyclic AMP-responsive element-binding protein (CREB)/activating transcription factor (ATF) proteins which bind this element were expressed in murine teratocarcinoma F9 cells to identify those capable of mediating Tax-dependent transactivation of human proenkephalin gene transcription [14].
• Stimulation of c-fos and c-jun gene expression and down-regulation of proenkephalin gene expression in C6 glioma cells by endothelin-1 [15].
• The scores of DSM-III-diagnosed post-traumatic stress disorder (PTSD) patients (N = 116), psychiatric patients who did not meet the criteria, and normals (N = 19) on the Keane, Malloy, and Fairbank (1984) PTSD and Penk Combat scales for the MMPI were compared [10].

Biological context of PENK

• In the present study, effects of response-dependent (contingent) and response-independent (noncontingent) cocaine administration on the PENK and PDYN gene expression in the rat forebrain have been directly compared using the "yoked" self-administration procedure [16].
• We also detect a polymorphism in one of the toad proenkephalin genes, mapping 1.5 kilobases (kb) 5' of the main exon; it is caused by an insertion/deletion of a 1-kb repetitive sequence which has the characteristics of a transposable element [12].
• DNA probes derived from rat and human proenkephalin and prodynorphin genes have been used to localize these two opiate neuropeptide genes on human chromosomes [17].
• In situ hybridization to metaphase chromosomes confirms these assignments and indicates regional localizations of proenkephalin to 8q23-q24 and of prodynorphin to 20p12-pter [17].
• The nucleotide sequence of a 6.8-kb region of human DNA containing the proenkephalin gene and flanking regions is reported [18].

Anatomical context of PENK

• In areas adjacent to the hypothalamus, cells that contain pre-PENK message occur in the nucleus basalis of Meynert, central nucleus of amygdala, bed nucleus of the stria terminalis, caudate nucleus, and putamen.(ABSTRACT TRUNCATED AT 400 WORDS)[19]
• Pre-PENK neurons are numerous in the infundibular nucleus, ventromedial nucleus, dorsomedial nucleus, caudal parvicellular portion of the paraventricular nucleus, tuberomammillary nucleus, lateral hypothalamus, and retrochiasmatic area [19].
• Pro-enkephalin (PENK) mRNA and PENK-derived peptides have been reported in lymphocytes, monocytes, and macrophages [20].
• Pre-PENK neurons occur in varying numbers in all hypothalamic nuclei except the mammillary bodies [19].
• Levels of the PENK mRNA remained unaltered in all the above-mentioned forebrain regions of rats receiving contingent or noncontingent cocaine injections [16].

Associations of PENK with chemical compounds

• Nerves displaying immunoreactivity (ir) for the proenkephalin (PRO-ENK) derivatives met-enkephalin (ME), leuenkephalin (LE), octapeptide, and heptapeptide (ordered in decreasing frequency) were present in the dorsolateral stroma of human prostate [21].
• Selective abolition of these patterns with salt, nuclease, or methanol is associated with liberation of immunoprecipitable proenkephalin into the extraction supernatant [1].
• Since levels of both vasopressin and beta-endorphin were very high, these deficits in proenkephalin B-peptides were selective and do not represent a generalized property of the human pituitary [22].
• Intrastriatal injection of this compound reduced the striatal PENK expression induced by haloperidol [23].
• In contrast, a group II mGluR agonist (2R,4R-APDC) administered intrastriatally reduced neither PENK expression nor the above-mentioned parkinsonian-like symptoms [23].

Enzymatic interactions of PENK

• Finally, furin cleaved proenkephalin to generate peptide B, an unidentified peak between the 18- and 5.3-kDa fragments, and a small amount of the 5.3-kDa fragment [24].

Regulatory relationships of PENK

• We report here that ATF-3 is coexpressed with the neuropeptide precursor proenkephalin in human neuroblastoma SK-N-MC cells [25].
• Nicotine, histamine, and vasoactive intestinal peptide each enhanced the rate of proenkephalin synthesis approximately 10-fold when examined between 16 and 32 h after the drug or hormone addition [26].

Other interactions of PENK

• However, pre-PDYN and pre-PENK cells differ from one another in distribution [19].
• Antiserum to beta-endorphin/beta-lipotropin, [Met]-enkephalin-Arg6-Gly7-Leu8, and human leumorphin were used to identify the POMC and the proenkephalin A and B systems, respectively [27].
• Secretion of met-enkephalin in the culture supernatant of IL-4- or IL-10-stimulated PBMC could not be observed, but proenkephalin A-derived met-enkephalin containing peptides could be demonstrated [28].
• Here we compare the structure and function of the proenkephalin cAMP-inducible enhancer with the mapped cAMP-inducible elements of the vasoactive intestinal polypeptide, somatostatin, and tyrosine hydroxylase genes and a putative cAMP-inducible element in the proto-oncogene c-fos [29].
• These results indicate that the sorting signal of POMC, proinsulin, and proenkephalin specifically interacts with Arg255 and Lys260 at a novel binding site, independent of the active site on CPE [30].

Analytical, diagnostic and therapeutic context of PENK

• Using in situ hybridization histochemistry, we studied the distribution of neurons that express preproopiomelanocortin (pre-POMC), preprodynorphin (pre-PDYN), and preproenkephalin (pre-PENK) gene transcripts within the human hypothalamus and surrounding structures [19].
• We conclude that endogenous opioids apparently exclusively derived from PRO-ENK may fulfill important comessenger functions in the fine regulation of prostatic stromal tonus and of local vascular perfusion [21].
• Nuclear proenkephalin, detected by immunofluorescence with a panel of antiproenkephalin monoclonal antibodies, is distributed predominantly in three patterns [1].
• PENK cDNA was amplified from newt brain in a RACE PCR targeting the 3' end of the newt delta opioid receptor (DOR) [31].
• Prostate stromal expression of PENK was verified by an antibody raised against a PENK peptide, by RT-PCR analysis of laser-capture microdissected stromal cells, and by database analysis [4].

References