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. (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.
Zhokhov
S S
SS
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.
Kostanyan
I A
IA
Gibanova
N V
NV
Surina
E A
EA
Rodionov
I L
IL
Storozheva
Z I
ZI
Proshin
A T
AT
Babichenko
I I
II
Lipkin
V M
VM
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000201:enzymology; D002470:Cell Survival / Q000187:drug effects; D005136:Eye Proteins / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000494:pharmacology*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D043265:Phosphatidylinositol Diacylglycerol-Lyase / Q000378:metabolism; D054801:Phosphoinositide Phospholipase C; D020011:Protective Agents / Q000494:pharmacology*; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D015843:Serpins / Q000494:pharmacology*; D019810:Sodium Azide / Q000494:pharmacology; D000099174:Pigment Epithelium-Derived Factor
D000262:Adenylyl Cyclases; D005136:Eye Proteins; D009363:Neoplasm Proteins; D009414:Nerve Growth Factors; D009842:Oligopeptides; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D020011:Protective Agents; D015843:Serpins; D019810:Sodium Azide; D000099174:Pigment Epithelium-Derived Factor; C091149:cell differentiation factor 8.2-kDa