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Basic Polypeptide (basic + polypeptide)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

INVOLVEMENT OF BOTH ENDOPLASMIC RETICULUM- AND MITOCHONDRIA-DEPENDENT PATHWAYS IN CARDIOTOXIN III-INDUCED APOPTOSIS IN HL-60 CELLS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2008
Ching-Ming Chien
SUMMARY 1Cardiotoxin (CTX) III, a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom, has been reported to have anticancer activity. In the present study, we investigated the mechanisms underlying the anticancer activity of CTX III in human leukaemia (HL-60 cells). 2Cardiotoxin III activated the endoplasmic reticulum (ER) pathway of apoptosis in HL-60 cells, as indicated by increased levels of calcium and glucose-related protein 78 (Grp78), and triggered the subsequent activation of µ-calpain and caspase 12. 3In addition, CTX III initiated the mitochondrial apoptotic pathway in HL-60 cells, as evidenced by an increased Bax/Bcl-2 ratio, the release of cytochrome c and activation of caspase 9. 4In the presence of 50 µmol/L Z-ATAD-FMK (a caspase 12 inhibitor) and 100 µmol/L Z-LEHD-FMK (a caspase 9 inhibitor), the CTX III-mediated activation of caspase 9 and caspase 3 was significantly reduced. There was no significant effect of the caspase 12 inhibitor Z-ATAD-FMK on mitochondrial cytochrome c release. 5Cardiotoxin III-mediated activation of caspase 12 was not abrogated in the presence of the caspase 9 inhibitor Z-LEHD-FMK, indicating that caspase 12 activation was not downstream of caspase 9. 6These results indicate that CTX III induces cell apoptosis via both ER stress and a mitochondrial death pathway. [source]

MECHANISMS OF CARDIOTOXIN III-INDUCED APOPTOSIS IN HUMAN COLORECTAL CANCER COLO205 CELLS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 3 2006
Chia-Houng Tsai
SUMMARY 1Cardiotoxin III (CTX III) is a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom. This is the first report on the mechanism of the anticancer effect of CTX III in human colorectal cancer Colo205 cells. 2Cardiotoxin III-induced Colo205 cell apoptosis was confirmed by DNA fragmentation (DNA ladder and sub-G1 formation) with an IC50 of 4 mg/mL at 48 h. 3Further mechanistic analysis demonstrate that CTX III induced the loss of mitochondrial membrane potential (Dym), cytochrome c release from mitochondria into the cytosol and activation of capase-9, caspase 3, as well as markedly enhancing the expression of Bax, but not Bcl-2, protein in the cells. Moreover, the CTX III-induced apoptosis was significantly blocked by the broad-spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. 4However, CTX III did not generate the formation of reactive oxygen species and anti-oxidants, including N -acetylcysteine, and catalase could not block CTX III-induced apoptosis in the Colo205 cells. 5Taken together, these results suggest that CTX III may induce apoptosis through a mitochondrial- and caspase-dependent mechanism and alteration of Bax/Bcl-2 ratio in human colorectal Colo205 cancer cells. [source]

CARDIOTOXIN III INDUCES APOPTOSIS IN K562 CELLS THROUGH A MITOCHONDRIAL-MEDIATED PATHWAY

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2005
Sheng-Huei Yang
SUMMARY 1.,Cardiotoxin (CTX) III is a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom. This is the first report on the mechanism of the anticancer effect of CTX III on human leukaemia K562 cells. 2.,Cardiotoxin III was found to inhibit the growth of K562 cells in a time- and dose-dependent manner, with an IC50 value of 1.7 ,g/mL, and displayed several features of apoptosis, including apoptotic body formation, an increase in the sub-G1 population, DNA fragmentation and poly (ADP-ribose) polymerase (PARP) cleavage. 3.,Investigation of the mechanism of CTX III-induced apoptosis revealed that treatment of K562 cells with CTX III resulted in the loss of mitochondrial membrane potential, cytochrome c release from mitochondria into the cytosol and activation of caspase-9 and caspase-3 and the subsequent cleavage of the caspase-3 substrate PARP; however, CTX III did not generate reactive oxygen species (ROS). 4.,Taken together, the results indicate that CTX III induces apoptosis in K562 cells through an ROS-independent mitochondrial dysfunction pathway. [source]

Neurotoxic Effects of Three Fractions Isolated from Tityus serrulatus Scorpion Venom

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2000
Ana Leonor A. Nencioni
Scorpion venoms contain low molecular weight basic polypeptides, neurotoxins, that are the principal toxic agents. These toxins act on ion channels, promoting a derangement that may result in an abnormal release of neurotransmitters. In the present study we investigated some of the effects of the F, H and J fractions isolated from Tityus serrulatus scorpion venom on the central nervous system of rodents. The venom was partially purified by gel filtration chromatography. The neurotoxic effect of these fractions was studied on convulsive activity after intravenous injection, and on electrographic activity and neuronal integrity of rat hippocampus when injected directly into this brain area. The results showed that intravenous injection of the F and H fractions induced convulsions, and intrahippocampal injection caused electrographic seizures in rats and neuronal damage in specific hippocampal areas. Fraction J injected intravenously reduced the general activity of mice in the open field but induced no changes when injected into the brain. These results suggest that scorpion toxins are able to act directly on the central nervous system promoting behavioural, electrographic and histological modifications. [source]