Productos de Laboratorio

Introduction to the Research Project

Introduction to NO/cGMP-signaling system

What's nitric oxide (usually abbreviated as NO)?:

NO is a free radical gas produced by cells in order to communicate with neighboring cells.

How is NO synthesized?:

Several enzymes (NO synthases; NOS) transform the aminoacid L-arginine (with molecular oxygen and NADPH as cosubstrates) into citrulline and NO. Two of these enzymes (NOS-1 and NOS-3; formerly known as nNOS and eNOS according to their main cell location: neurons and endothelium) are constitutive, that is they are normally expressed by the producer cell. Another type (NOS-2, Type II NOS or also known as iNOS) is an inducible form. This NOS is not expressed in resting cells and producer cell must be previously stimulated with certain substances, such as endotoxin or cytokines, to synthesize it. NOS-2 usually releases much more NO than the constitutive forms.

How does NO exert its actions?:

NO enters the second cell (diana) and activates soluble guanylyl cyclase (sGC; also known as soluble guanylate cyclase). This enzyme synthesize cyclic GMP (cGMP; guanosine 3':5'-cyclic monophosphate) from GTP (nucleotide that is also one of the components of DNA). cGMP modulates the activity of protein kinase G (PKG), two cyclic nucleotide phosphodiesterases (PDE2 and PDE3) and some ion channels. Although cGMP seems to be the main mediator of NO effects, NO can also act through protein nitrosylation, interaction with transition metals or other free radicals, direct modification of DNA, etc.

And where?:

NO has been shown to be especially relevant in brain, in the vascular system and in the immune system. However, its synthetic enzymes are amply distributed in many organs. Its importance is manifested by the big number of diseases in which NO can play a role: diabetes mellitus, erectile dysfunction, myocardial infarction, ...

Introduction to Myocardial Infarction

Any cell of the organism should receive a constant supply of oxygen and other nutrients. This is achieved thanks to a complex net of blood vessels. Heart, besides being responsible of pumping blood throughout the whole body, has its own arteries (coronary arteries) and capillaries that irrigate every cardiac muscle cell.

When the pass of blood through one of these coronary vessels is blocked, some cells of the myocardial tissue are exposed to an oxygen pressure and a nutrient concentration below the usual levels. These cells are suffering a condition known as ischemia. Tissues that perform an arduous and permanent work as brain or heart are especially sensitive to this situation. If ischemia is not solved in a short time, cells die and the part of the heart affected constitutes an infarcted region.