A biologically active fragment of the differentiation factor of the HL-60 line cells: Identification and properties

Коstanyan, I. A.; Astapova, M. V.; Navolotskaya, E. V.; Lepikhova, T. N.; Dranitsyna, S. M.; Telegin, G. B.; Rodionov, I. L.; Байдакова, Л. К.; Zolotarev, Yu. A.; Molotkovskaya, I. M.; Липкин, В. М.

doi:10.1007/bf02758614

Cited by 15 publications

(11 citation statements)

References 9 publications

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“…Endogenous levels of the hormone HLDF in adult rat blood and brain structures was determined (Sewell et al, 2005). Hexapeptide HLDF-6 fully reproduced the differentiation activity of the full-sized factor (Kostanyan et al, 1994, 2000). In animals the central and systemic administration of HLDF-6 in doses of 3–30 μg/kg caused better formation and retention of long-term memory, which confirms high nootropic activity of the peptide (Kostanyan et al, 2009).…”

Section: Introductionmentioning

confidence: 90%

Anxiolytic activity of the neuroprotective peptide HLDF-6 and its effects on brain neurotransmitter systems in BALB/c and C57BL/6 mice

et al. 2016

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This study is focused on a new amide derivative of the peptide HLDF-6 (Thr-Gly-Glu-Asn-His-Arg). This hexapeptide is a fragment of Human Leukaemia Differentiation Factor (HLDF). It displays a broad range of nootropic and neuroprotective activities. We showed, for the first time, that the peptide HLDF-6-amide has high anxiolytic activity. We used 'open field' and 'elevated plus maze' tests to demonstrate anxiolytic effects of HLDF-6-amide (0.1 and 0.3 mg/kg intranasally), which were comparable to those of the reference drug diazepam (0.5 mg/kg). Five daily equipotent doses of HLDF-6-amide selectively mitigated anxiety and increased the density of NMDA receptors in the hippocampus of stress-susceptible BALB/c mice, and had no effect on stress-resilient C57BL/6 mice. The subchronic administration of HLDF-6-amide showed no effect on the density of GABAA and nicotine receptors but was accompanied by a nonselective decrease of the 5-HT2A serotonin receptor density in frontal cortex of both strains. The mechanism of the specific anxiolytic activity of HLDF-6-amide may include its action on the NMDA-glutamatergic receptor system of the hippocampus and on serotonin 5-HT2A-receptors in the prefrontal cortex. The psychotropic activity of HLDF-6-amide is promising for its introduction to medical practice as a highly effective anxiolytic medicine for mental and neurological diseases.

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Section: Introductionmentioning

confidence: 90%

Anxiolytic activity of the neuroprotective peptide HLDF-6 and its effects on brain neurotransmitter systems in BALB/c and C57BL/6 mice

et al. 2016

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“…Research on human leukaemia differentiation factor (HLDF), which we were the irst to discover and isolate [4], revealed a hexapeptide fragment, Thr-Gly-Glu-Asn-His-Arg (HLDF-6), that reproduced the differentiating effects of the full-size factor. Direct evidence of the neuroprotective effects of HLDF-6 were obtained from experiments in a primary culture of neuronal cells from the hippocampus and cerebellum as well as in immunocompetent cells [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Comparative study of carboxylate and amide forms of HLDF-6 peptide: Neuroprotective and nootropic effects in animal models of ischemic stroke

Bogachuk¹,

Сторожева²,

Proshin³

et al. 2019

J Neurosci Neurol Disord

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Aim: The work was to perform a comparative study of the neuroprotective and nootropic activities of two pharmaceutical substances, the HLDF-6 peptide and its amide form (HLDF-6-NH 2). Materials and Methods: We used in the study healthy adult male Wistar rats aged 180-200 days weighing 280-300 g. We modelled ischemic stroke in rats by chronical occlusion of carotid arteries. Solutions of the HLDF-6-NH 2 and HLDF-6 peptides were administered intranasally. Cognitive functions we assessed with Novel object recognition test and Morris maze. Results: The amide form of HLDF-6 peptide is more effi cient: the neuroprotective activity of HLDF-6-NH 2 , evaluated by improvement of cognitive functions in animals, surpassed that of the native HLDF-6 peptide. A dose of 250 μg/kg of HLDF-6-NH 2 peptide resulted in practically complete restoration of the disturbed functions. In the model of ischemic stroke, the amide form of the peptide signifi cantly excelled the reference substance mexidol both in the effective dose and biological activity. Conclusion: The results of study of the agent allow hoping for its success in further clinical investigation. In view of high demand for the agent and in case of successful clinical trials, it will surely become widely used in clinical practice in treatment of IS.

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“…This peptide exhibits an anti-apoptotic activity and protects cells against beta-amyloid (βA) peptide, sodium azide, ceramide, ethanol, cold stress, and hypoxia. HLDF-6 peptide enhances the viability of early mouse embryos in vitro [ 4 - 7 ].…”

Section: Introductionmentioning

confidence: 99%

Studying the Specific Activity of the Amide Form of HLDF-6 Peptide using the Transgenic Model of Alzheimer’s Disease

et al. 2017

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The neuroprotective and nootropic activities of the amide form (AF) of the HLDF-6 peptide (TGENHR-NH2) were studied in transgenic mice of the B6C3-Tg(APPswe,PSEN1de9)85Dbo (Tg+) line (the animal model of familial Alzheimer’s disease (AD)). The study was performed in 4 mouse groups: group 1 (study group): Tg+ mice intranasally injected with the peptide at a dose of 250 μg/kg; group 2 (active control): Tg+ mice intranasally injected with normal saline; group 3 (control 1): Tg- mice; and group 4 (control 2): C57Bl/6 mice. The cognitive functions were evaluated using three tests: the novel object recognition test, the conditioned passive avoidance task, and the Morris water maze. The results testify to the fact that the pharmaceutical substance (PhS) based on the AF of HLDF-6 peptide at a dose of 250 μg/kg administered intranasally efficiently restores the disturbed cognitive functions in transgenic mice. These results are fully consistent with the data obtained in animal models of Alzheimer’s disease induced by the injection of the beta-amyloid (βA) fragment 25-35 into the giant-cell nucleus basalis of Meynert or by co-injection of the βA fragment 25-35 and ibotenic acid into the hippocampus, and the model of ischemia stroke (chronic bilateral occlusion of carotids, 2VO). According to the overall results, PhS based on AF HLDF-6 was chosen as an object for further investigation; the dose of 250 μg/kg was used as an effective therapeutic dose. Intranasal administration was the route for delivery.

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A biologically active fragment of the differentiation factor of the HL-60 line cells: Identification and properties

Cited by 15 publications

References 9 publications

Anxiolytic activity of the neuroprotective peptide HLDF-6 and its effects on brain neurotransmitter systems in BALB/c and C57BL/6 mice

Anxiolytic activity of the neuroprotective peptide HLDF-6 and its effects on brain neurotransmitter systems in BALB/c and C57BL/6 mice

Comparative study of carboxylate and amide forms of HLDF-6 peptide: Neuroprotective and nootropic effects in animal models of ischemic stroke

Studying the Specific Activity of the Amide Form of HLDF-6 Peptide using the Transgenic Model of Alzheimer’s Disease

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