PEDF - A Noninhibitory Serpin with Neurotrophic Activity.

The pigment epithelium-derived factor (PEDF) is a glycoprotein with a molecular weight of 50 kDa belonging to the noninhibitory serpin family. It regulates several physiological processes, such as stimulation of retinoblastoma cell differentiation into neuron cells, and facilitation of the growth and viability of photoreceptor cells and neurons of the central nervous system. Moreover, this factor protects neuronal cells against apoptosis.

Antitumor and immunomodulating effects of a fragment of HL-60 cell differentiation factor in mice with lewis pulmonary carcinoma.

A six-member HLDF6 peptide, fragment of HL-60 cell differentiation factor, exhibited antimetastatic and immunomodulating effects.

Hemodynamic effects of peptide fragments of differentiation factor HLDF.

Hemodynamic activity of peptides from differentiation factor HLDF (promyelocytic HL-60 line) was studied on WKY and SHR-SP rats. Intravenous infusion of the test peptides was accompanied by changes in blood pressure and heart rate, which depended on the structure of peptides and functional activity of the organism and differed in normotensive and hypertensive animals.

Granulocyte differentiation inducer, hexapeptide HLDF-6, decreases cytotoxic effect of tumor necrosis factor on HL-60 cell line.

The effect of hexapeptide HLDF-6, the granulocytic differentiation inducer, on the tumor necrosis factor alpha (TNF-alpha)-induced differentiation and apoptosis of human promyelocytic leukemia HL-60 cells has been investigated. Costimulation of HL-60 cells with HLDF-6 and TNF-alpha enhanced granulocyte differentiation, whereas the level of monocyte differentiation remained unchanged; however, the cytotoxic action of TNF-alpha on these cells decreased. The protective effect of HLDF-6 peptide did not depend on activation of NF-kappaB (nuclear transcription factor).

Lysozyme amyloid oligomers and fibrils induce cellular death via different apoptotic/necrotic pathways.

Among the newly discovered amyloid properties, its cytotoxicity plays a key role. Lysozyme is a ubiquitous protein involved in systemic amyloidoses in vivo and forming amyloid under destabilising conditions in vitro. We characterized both oligomers and fibrils of hen lysozyme by atomic force microscopy and demonstrated their dose (5-50 microM) and time-dependent (6-48 h) effect on neuroblastoma SH-SY5Y cell viability.

Hexapeptides HLDF-6 and PEDF-6 restore memory in rats after chronic intracerebroventricular treatment with beta-amyloid peptide Abeta(25-35).

Effects of homologous peptides HLDF-6 and PEDF-6 on behavior of animals with experimental Alzheimer's disease induced by chronic intracerebroventricular administration of beta-amyloid peptide Abeta(25-35) were studied in the zoosocial recognition test and Morris water maze. Peptides HLDF-6 and PEDF-6 possessed neuroprotective activity and counteracted the toxic effect of Abeta(25-35). Peptides HLDF-6 and PEDF-6 mainly improved long-term memory and working memory, respectively.

Experimental model of hemorrhagic stroke: rabbit immunization with HL-60 promyelocytic cell differentiation factor.

Rabbits immunized with synthetic HLDF differentiation factor developed hemorrhagic stroke with thrombosis of small cerebral vessels and destruction of vascular endotheliocytes. The severity of stroke correlated with serum level of antibodies to differentiation factor. The role of different sites of HLDF molecule in the induction of clinical signs of hemorrhagic stroke was studied.

Intermediate amyloid oligomers of lysozyme: Is their cytotoxicity a particular case or general rule for amyloid?

In the current study we investigated the molecular mechanisms of cytotoxicity of amyloid oligomers of horse milk lysozyme. We have shown that lysozyme forms soluble amyloid oligomers and protofibrils during incubation at pH 2.0 and 4.

Cytotoxicity of albebetin oligomers depends on cross-beta-sheet formation.

Prefibrillar cytotoxicity was suggested as a common amyloid characteristic. We showed two types of albebetin prefibrillar oligomers are formed during incubation at pH 7.3.

Amyloidogenic properties of the artificial protein albebetin and its biologically active derivatives. The role of electrostatic interactions in fibril formation.

The artificial protein albebetin (ABB) and its derivatives containing biologically active fragments of natural proteins form fibrils at physiological pH. The amyloid nature of the fibrils was confirmed by far UV circular dichroism spectra indicating for rich beta-structure, thioflavin T binding assays, and examination of the obtained polymers by atomic force microscopy. Fusing of short peptides--octapeptide of human alpha(2)-interferon (130-137) or hexapeptide HLDF-6 (41-46) of human leukemia differentiation factor--with the N-terminus of ABB led to increased amyloidogenicity of the protein: the rate of fibril formation increased and the morphology of fibrils became more complex.

Does the human leukaemia differentiation factor fragment HLDF6 improve memory via brain DNA and protein synthesis?

The novel human differentiating factor peptide fragment HLDF6 (Thr-Gly-Glu-Asn-His-Arg) was synthesized and purified. HLDF6 (0.1mg/kg i.

HLDF-6 peptide affects behavioral reactions and organism functions dependent on androgen hormones in normal and castrated male mice.

The hexapeptide Thr-Gly-Glu-Asn-His-Arg (HLDF-6), which was first identified as an active fragment of the human leukemia differentiation factor (HLDF) molecule, displays differentiation-inducing, neuroprotective and anti-drug abuse activities. Most of its in vivo effects were revealed only on male animals. We have studied HLDF-6 effects on a variety of organism functions and behavioral reactions, which are known to be dependent on androgen steroid hormones, both on castrated and normal (sham-operated) animals.

HLDF-6 peptide relieves symptoms of abstinence syndrome during experimental opium abuse.

Experiments were performed on rats with opium abuse induced by chronic administration of morphine in increasing doses. We studied the effect of HLDF-6 peptide on symptoms of naloxone abstinence. Repeated administration of HLDF-6 peptide in a dose of 0.

Different mechanisms of protective and differentiative activities of homological peptides TGENHR and TQVEHR.

Previously we identified a six-membered fragment 354TQVEHR359 of the C-terminal part of the PEDF (Pigment Epithelium-Derived Factor) differentiation factor molecule that shares homology with fragment 41TGENHR46 of the HLDF (Human Leukemia Differentiation Factor) differentiation factor molecule, which is responsible for its differentiation activity. HLDF has been isolated from the culture medium of human promyelocytic leukemia cell line HL-60. Hexapeptides HLDF-6 (TGENHR) and PEDF-6 (TQVEHR) corresponding to these HLDF and PEDF molecule fragments, which were previously shown to induce cell differentiation (Kostanyan et al.

Fibrillation of carrier protein albebetin and its biologically active constructs. Multiple oligomeric intermediates and pathways.

We showed that the genetically engineered carrier-protein albebetin and its biologically active constructs with interferon-alpha(2) octapeptide LKEKKYSP or differentiation factor hexapeptide TGENHR are inherently highly amyloidogenic at physiological pH. The kinetics of fibrillation were monitored by thioflavine-T (ThT) binding and the morphological changes by atomic force microscopy. Fibrillation proceeds via multiple pathways and includes a hierarchy of amyloid structures ranging from oligomers to protofilaments and fibrils.

Autoimmune responses to amyloid structures of Abeta(25-35) peptide and human lysozyme in the serum of patients with progressive Alzheimer's disease.

We have found an increased level of serum antibodies to the prefibrillar structures of both Abeta(25-35) peptide and human lysozyme in Alzheimer's disease (AD) patients compared to age-matched controls, indicating that autoimmunity is implicated in AD. In the serum of AD patients with a long-term duration (>15 years) the titer of serum antibodies to aggregates of Abeta(25-35) peptide increased by approximately 5-fold, whilst the antibody titer to lysozyme protofilaments decreased by approximately 8-fold compared to patients with AD duration of <5 years. The content of immunoglobulins of the A, G and M types declined, particularly in AD duration of >15 years.

Use of HLDF-6 peptide for correction of disturbances in the endogenous opioid system in offspring of morphine-tolerant animals.

We studied the effect of bioactive peptide HLDF-6 on functional activity of the endogenous antinociceptive system in the offspring of morphine-tolerant animals. Disturbances in this system included changes in the thermonociceptive threshold and enkephalinase A activity in various brain structures. The peptide acted as a potent regulator of the homeostasis in systems responsible for the synthesis and catabolism of endogenous opioids.

Soluble Fas antigen in the serum of patients with colon cancer.

Serum concentration of soluble Fas antigen (sFas) was measured in 60 normal subjects and 33 patients with colon cancer. The incidence of sFas detection and its serum content were higher in patients with colon cancer compared to normal subjects. No relationships between the incidence and level of sFas and patient's sex, age, duration and stage of the disease were found.

Leptin and apoptosis inhibitor soluble Fas antigen in the serum of patients with osteosarcoma and neuroectodermal bone tumors.

Serum contents of leptin and soluble Fas antigen were measured in 28 patients with osteosarcoma, 7 with neuroectodermal bone tumors, and 17 healthy subjects. The incidence and levels of soluble Fas antigen in patients with osteosarcoma and neuroectodermal bone tumors were higher than in healthy subjects and did not depend on sex and age in both healthy subjects and patients. Serum concentration of leptin in women was higher than in men (both in healthy controls and patients) and was lower in healthy subjects compared to patients with osteosarcoma and neuroectodermal bone tumors.