BECAUSE THE BLOOD AND PLASMA OF YOUNG DONORS ACTIVATE GENES THAT INDUCE THE CELLULAR REPROGRAMMATION? "THIRD PART"

BECAUSE THE BLOOD AND PLASMA OF YOUNG DONORS ACTIVATE GENES THAT INDUCE THE CELLULAR REPROGRAMMATION?

"THIRD PART"

Rodolfo Sixto Negri (1)

Nuclear receptors that are activated by hormones or other proteins activate specific DNA receptors called hormone-sensitive elements (HREs), which are DNA sequences that are located in the promoter region of the genes that are activated by the Hormone-Receptor complex. o Protein-Receptor [PR]. As this complex activates the transcription of certain genes, these hormones or proteins are also called inducers of gene expression. Activation of gene transcription is much slower than signals that directly affect existing proteins. As a consequence, the effects of certain hormones or proteins that bind to nuclear receptors occur in the long term. However, the transduction signal through soluble receptors affects only some proteins.

The receptors linked to enzymes, are a set of receptors that base their functional model on the increase of enzymatic activity. A protein binds to the receptor and causes a specific enzymatic activity at the intracellular level:

Receptors of the epidermal growth factor: ErbB

Receptors of the neurotropic factor derived from the glial cell line: GFRa

Receptors of natriuretic peptides: NPR

Receptors of neurotrophins: Trk.

Transmembrane receptors:

1- With intrinsic tyrosine kinase activity, are receptors of most of the growth factors and the insulin receptor.

These receptors have an extracellular ligand-binding domain, a transmembrane domain and an intracellular domain with intrinsic tyrosine kinase activity. When it binds to the ligand, the receptor dimerizes, which induces the autophosphorylation of the tyrosines of the intracellular domain and activates the tyrosine kinase, which phosphorylates (activates) many effector molecules in cascade, in a form or by adapter proteins.

These receptors can activate different signaling cascades such as cascades of MAP Kinases (Mitogen-Activated-Protein), with activation of the GTP binding protein called Ras, synthesis and activation of transcription factors such as FOS and JUN, which stimulate the production of new GROWTH FACTORS, of RECEIVERS for said factors and of PROTEINS that control the entry into the cell in the cell cycle.

The PI3K cascade (phosphoinositol 3-kinase), which activates AKT kinase, is involved in cell proliferation and cell survival by inhibiting apoptosis.

2-Receptors that lack intrinsic activity that recruit kinases, in this group include the receptors of many cytokines, such as IL-2, IL-3, Interferon alpha, beta and gamma, erythropoietin (EPO), growth hormone and prolactin . The transmission of the signal of these receptors causes the activation of members of the family called JAK (Janus kinases), these kinases activate cytoplasmic transcription factors called STATs (Signal Transducers and activation of transcription), which are translocated to the nucleus and activate the transcription of specific genes. In other cases, these receptors activate the MAP kinase cascade.

3-The receptors coupled to G proteins, base their functional model on signal transduction: a protein binds to the receptor and generates a cascade of signals that leads to a specific biological behavior. There are 6 subtypes of receptors coupled to G proteins, which are distinguished by their protein similarity, mechanism or function.

Among them the Frizzled receiver. (Kumar, MBBS et.al 2009, Abul Abbas, MBBS et al., 2009, Nelson Fausto, MD and Jon Aster, MD (2009).

(1) -Bioquimico-MUBM & BIOMEDICINE

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