Epithalon Tetra Peptide Sequence: alanyl-glutamyl-aspartyl-glycine
Molecular Formula: C14H22N4O9
Molecular Weight: 390.34588

Epitalon Tetra Peptide

Epithalon  is a peptide used to regulate the cell cycle through up-regulation of telomerase activity. The sequence of amino acids in the peptide is Alanine-Glutamate-Asparagine-Glycine. Animal studies have been done on the effects of Epithalon on suppression of spontaneous mammary tumors and spontaneous carcinogenesis. Studies have shown that the mode of action of Epithalon involves suppression of oncogene expression and modification of telomerase activity. A summary of the studies and research on telomerase is provided below.

Telomerase is a specific RNA (ribonucleic acid)-dependent polymerase that elongates and maintains the length of telomeres by adding tandem repeats on the chromosomal 3′ end. The enzyme is composed of two parts: an RNA component which supplies the telomere template for elongation, and the catalytic subunit which possesses reverse transcriptase activity. These two parts work in tandem to avert telomere attrition especially in somatic cells. In vitro experiments have shown that telomere elongation promotes indefinite cellular proliferation and that suppression of telomerase activity promotes apoptosis of neoplastic cells. However, these studies have also shown that maintenance of telomere length within a range of 15-20 kilobase pairs does prevent tumorigenesis. All the research and studies done concerning telomerase do show that telomerase activity is limited to cell division through its action of stabilizing the telomere length.

Telomeres are located at either ends of a chromosome, and they do protect the adjacent gene sequence from shortening due to repeated replication cycles. Elongation of telomeres enables senescent cells to stabilize their telomeric length. However, excess elongation would enable such cells to exceed their Hayflick limit via evasion of apoptosis or the post-mitotic phase; and therefore, such cells have the potential of becoming immortal and this predisposes them to neoplastic transformation.

Human telomeres are made up of tandem repeats of the nucleotide sequence TTAGGG that form a T loop structure when associated with telomere-binding proteins. The T loop structure ensures the integrity of the telomeres by protecting them from constitutive degradation. These tandem repeats do shorten as a consequence of repeated chromosomal replication cycles. Such shortening is due to the inability of DNA polymerase to repeatedly replicate the nucleotides located in the T loop region. This leads to senescence or growth arrest, and a critically shortened telomere does induce a p53-mediated DNA checkpoint reaction. Some cells do evade senescence if they have nonfunctional p53 and/or pRb, but cell death still occurs due to either lethal DNA rearrangements or chromosomal fusion. Thus, evasion of telomere-mediated senescence is the main way that cells use to avert premature senescence and apoptosis. This occurs only when telomerase activity is up-regulated. Telomerase elongation leads to stabilization of the genotype as the rate of gene mutation is maintained within normal limits. However, an increase in the rate of apoptosis leads to a proportionate increase in cellular regeneration rate, and this causes an increase in the number of sporadic gene mutations that occur thus predisposing the person to pro-neoplastic mutations.

Current studies show that telomere shortening is associated with chronic diseases such as pulmonary fibrosis, coronary artery disease, diabetes mellitus and Alzheimer’s disease, though their findings are still considered inconclusive. Based on the findings of these studies, it can be theorized that Epithalon could prevent the development of these diseases.

Wholesale DSIP 10mg

Delta sleep-inducing peptide, abbreviated DSIP, is a neuropeptide that when infused into the mesodiencephalic ventricle of recipient rabbits induces spindle and delta EEG activity and reduced motor activities. Its aminoacid sequence is Тrр-Аlа-Gly-Gly-Asp-Ala-Ser-Gly-Glu.

Discovery

Delta sleep-inducing peptide was first discovered in 1974 by the Swiss Schoenenberger-Monnier group who isolated it from the cerebral venous blood of rabbits in an induced state of sleep. It was primarily believed to be involved in sleep regulation due to its apparent ability to induce slow-wave sleep in rabbits, but studies on the subject have been contradictory.

Delta-sleep-inducing peptide (DSIP)-like material has also been found in human breast milk.

Structure and Interactions

DSIP is an amphiphilic peptide of molecular weight 850 daltons with the amino acid motif: N-Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu-C.

It has been found in both free and bound forms in the hypothalamus, limbic system and pituitary as well as various peripheral organs, tissues and body fluids. In the pituitary it co-localises with many peptide and non-peptide mediators such as corticotropin-like intermediate peptide (CLIP), adrenocorticotrophic hormone (ACTH), melanocyte-stimulating hormone (MSH), thyroid-stimulating hormone (TSH) and melanin concentrating hormone (MCH). It is abundant in the gut secretory cells and in the pancreas where it co-localizes with glucagon.

In the brain its action may be mediated by NMDA receptors. In another study Delta sleep-inducing peptide stimulated Acetyltransferase activity through receptors in rats.

In vitro it has been found to have a low molecular stability with a half life of only 15 minutes due to the action of a specific aminopeptidase-like enzyme. It has been suggested that in the body it complexes with carrier proteins to prevent degradation, or exists as a component of a large precursor molecule,[9] but as yet no structure or gene has been found for this precursor.

Evidence supports the current belief that it is regulated by glucocorticoids. Gimble et al. suggest that DSIP interacts with components of the MAPK cascade and is homologous to glucocorticoid-induced leucine zipper (GILZ). GILZ can be induced by Dexamethasone. It prevents Raf-1 activation, which inhibits phosphorylation and activation of ERK.

Function

Many roles for DSIP have been suggested following research carried out using peptide analogues with a greater molecular stability  and through measuring DSIP-like immunological (DSIP-LI) response by injecting DSIP antiserum and antibodies.

Roles in endocrine regulation

Decreases basal corticotropin level and blocks its release. Stimulates release of luteinizing hormone (LH).Stimulates release of somatoliberin and somatotrophin secretion and inhibits somatostatin secretion.

Roles in physiological processes

Can act as a stress limiting factor.

May have a direct or indirect effect on body temperature and alleviating hypothermia.

Can normalize blood pressure and myocardial contraction.

It has been shown to enhance the efficiency of oxidative phosphorylation in rat mitochondria in vitro, suggesting it may have antioxidant effects.

There is also conflicting evidence as to its involvement in sleep patterns. Some studies suggest a link between DSIP and slow-wave sleep (SWS) promotion and suppression of paradoxical sleep,  while some studies show no correlation. Stronger effects on sleep have been noted for the synthesized analogues of DSIP.

It may have an impact on human lens epithelial cell function via the MAPK pathway, which is involved in cell proliferation, differentiation, motility, survival, and apoptosis.

Roles in Disease and Medicine

It has been found to have anticarcinogenic properties. In a study on mice, injecting a preparation of DSIP over the mice’s lifetime decreased total spontaneous tumor incidence 2.6-fold.

The same study found it to also have geroprotective effects: it slowed down the age-related switching-off of oestrous function; it decreased by 22.6% the frequency of chromosome aberrations in bone marrow cells and it increased by 24.1% maximum life span in comparison with the control group.

Levels of DSIP may be significant in patients diagnosed with major depressive disorder (MDD). In several studies, levels of DSIP in the plasma and cerebrospinal fluid are significantly deviated from the norm in patients with MDD, though there are contradictions as to whether levels are higher or lower than healthy control patients.

Studies have demonstrated a direct link between GILZ expression (homologous to DSIP) and adipogenesis which has links to obesity and metabolic syndrome.

In studies on rats with metaphit-induced epilepsy DSIP acted as an anticonvulsant, significantly decreasing the incidence and duration of fits suggesting DSIP as a potential treatment for epilepsy.

DSIP has been found to have an analgesic effect. In studies on mice it was found to have a potent antinociceptive effect when administered intracerebroventricularly or intracisternally (see: Route of administration).

Due to its possible effects on sleep and nociception, trials have been carried out to determine whether DSIP can be used as an anaesthetic. One such study found that administration of DSIP to humans as an adjunct to isoflurane anaesthesia actually increased the heart rate and reduced the depth of anaesthesia instead of deepening it as expected.

Low plasma concentrations of DSIP have been found in patients with Cushing’s syndrome.[38] In Alzheimer’s patients levels of DSIP have been found to be slightly elevated, though this is unlikely to be causal.

A preparation of DSIP, Deltaran, has been used to correct central nervous system function in children after antiblastomic therapy. Ten children aged 3-16 years were given a ten-day course of Deltaran and their bioelectric activity recorded. It was found that the chemotherapy-induced impairment in the bioelectrical activity of 9 out of the 10 children was reduced by administration of DSIP.

DSIP can act antagonistically on opiate receptors to significantly inhibit the development of opioid and alcohol dependence and is currently being used in clinical trials to treat withdrawal syndrome. In one such trial it was reported that in 97% of opiate-dependent and 87% of alcohol-dependent patients the symptoms were alleviated by DSIP administration.

In some studies administration of DSIP has alleviated narcolepsy and normalized disturbed sleeping patterns.

Safety and possible side-effects of long-term DSIP use hasn’t been established in clinical research studies.