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, whic...

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Bibliographic Details
Published in:Biochemistry (Moscow) 2004-08, Vol.69 (8), p.861-869
Main Authors: Zhokhov, S S, Kostanyan, I A, Gibanova, N V, Surina, E A, Rodionov, I L, Storozheva, Z I, Proshin, A T, Babichenko, I I, Lipkin, V M
Format: Article
Language:English
Subjects:
Adenylate cyclase
Adenylyl Cyclases - metabolism
Animals
Cell Hypoxia - drug effects
Cell Hypoxia - physiology
Cell Membrane - enzymology
Cell Survival - drug effects
Cerebellum
Eye Proteins - pharmacology
HL-60 Cells
Humans
Hypoxia
Neoplasm Proteins - pharmacology
Nerve Growth Factors - pharmacology
Oligopeptides - pharmacology
Peptides
Phosphatidylinositol
Phosphatidylinositol Diacylglycerol-Lyase - metabolism
Phosphoinositide Phospholipase C
Protective Agents - pharmacology
Proteins
Purkinje Cells - drug effects
Purkinje Cells - metabolism
Purkinje Cells - pathology
Rats
Serpins - pharmacology
Sodium Azide - pharmacology
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Summary: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. (2000) Russian Journal of Bioorganic Chemistry, 26, 505-511), also have neuroprotective properties. Both peptides prevent degeneration of Purkinje cells of rat cerebellar vermis upon chemical hypoxia induced by sodium azide in vivo; this effect is also observed on a behavioral level. Peptide HLDF-6 but not PEDF-6 promotes survival of HL-60 cells upon chemical hypoxia. Peptides HLDF-6 and PEDF-6 affect different second messenger biosynthesis systems in HL-60 cells. HLDF-6 diminishes cyclic AMP level in those cells due to adenylate cyclase inhibition, while PEDF-6 inhibits phosphatidylinositol-specific phospholipase C stimulated by aluminum tetrafluoride anions.
ISSN:0006-2979
1608-3040
DOI:10.1023/B:BIRY.0000040217.76635.43