Biomedical subjects

E Herbert

Publications and source records attributed to E Herbert.

111 records · Page 7Linked to original sources

PubMedDate not supplied

A cyclic AMP- and phorbol ester-inducible DNA element.

Many cellular processes are regulated by hormones and neurotransmitters which interact with cell-surface receptors to produce intracellular second messengers that activate protein kinases. Cyclic (c) AMP is a second messenger whose intracellular level is determined by receptor-mediated activation or inhibition of adenylate cyclase. Phorbol esters directly activate protein kinase C, a Ca2+ and phospholipid-dependent protein kinase and a component of a different second messenger system, the phosphatidylinositol pathway. 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. Here we report that cAMP analogues and activators of adenylate cyclase regulate a proenkephalin-chloramphenicol acetyl transferase fusion gene when transiently expressed in tissue culture cells. Phorbol ester regulates the fusion gene in a similar fashion, but requires the presence of phosphodiesterase inhibitors for large effects. 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. This highly conserved region is composed of three closely related 12-bp sequences and has properties similar to those of previously characterized transcriptional enhancers.

Acetyltransferases↗

PubMedDate not supplied

Cloning and sequence analysis of cDNA for bovine carboxypeptidase E.

Carboxypeptidase E (enkephalin convertase) was first identified as the carboxypeptidase B-like enzyme involved in the biosynthesis of enkephalin in bovine adrenal chromaffin granules. A similar enzyme is present in many brain regions and in purified secretory granules from rat pituitary and rat insulinoma. Within the secretory granules, carboxypeptidase E (CPE) activity is found in both a soluble and a membrane-bound form, which differ slightly in relative molecular mass (Mr). Here, to investigate whether the CPE activities in the various tissues are produced from a single gene, purified CPE was partially sequenced and oligonucleotide probes were used to isolate a clone encoding CPE from a bovine pituitary complementary DNA library. This cDNA hybridizes to bovine pituitary poly(A)+ RNAs of approximately 3.3, 2.6 and 2.1 kilobases (kb), with the 3.3-kb messenger RNA the predominant species. The predicted amino-acid sequence of the cDNA clone contains the partially determined sequences of CPE, several pairs of basic amino acids and displays some homology with both carboxypeptidases A and B. Restriction analysis of bovine genomic DNA suggests only one gene for CPE. This is consistent with a broad role for CPE in the biosynthesis of many neuropeptides.

Amino Acid Sequence↗

PubMedDate not supplied

Clinical aspects and physiopathology of Brugada syndrome: review of current concepts.

Brugada syndrome (BS) is an inherited cardiac disorder characterized by typical electrocardiographic patterns of ST segment elevation in the precordial leads, right bundle branch block, fast polymorphic ventricular tachycardia in patients without any structural heart disease, and a high risk of sudden cardiac death. The incidence of BS is high in male vs. female (i.e., 8-10/1: male/female). The disorder is caused by mutations in the SCN5A gene encoding Nav1.5, the cardiac sodium channel, which is the only gene in which mutations were found to cause the disease. Mutations in SCN5A associated with the BS phenotype usually result in a loss of channel function by a reduction in Na+ currents. We review the clinical aspects, risk stratification, and therapeutic management of this important syndrome.

Brugada Syndrome↗