|Table of Contents|

The Effect of Melittin on Rat Red Blood Cells and Its Mechanism(PDF)

《南京师大学报（自然科学版）》[ISSN:1001-4616/CN:32-1239/N]

Issue:
2015年02期
Page:
86-
Research Field:
生命科学
Publishing date:

Info

Title:
The Effect of Melittin on Rat Red Blood Cells and Its Mechanism
Author(s):
Shi Wei; Li Caiyun; Chen Yuqing
School of Life Sciences,Nanjing Normal University,Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology,Nanjing 210023,China
Keywords:
Melittin; hemolysis; sialic acid; carbohydrates; cholesterol
PACS:
Q26
DOI:
-
Abstract:
Melittin is an antibacterial peptide with variety of biologically activities including highly effective against bacteria,fungi and tumor cells. However,its highly hemolysis activity limits the application as antibacterial and anticancer drugs. This paper deeply analyzed the mechanism of action of Melittin to rat red blood cells,especially for cellular mechanisms. The result showed that Melittin induced a pore-forming on erythrocyte membrane,inhibited the activity of intracellular ATPase. Sialic acid moieties of glycoproteins or glycolipids interact with Melittin mediated hemolytic activity of Melittin. Plasma membrane cholesterol may also interact with Melittin and influence hemolytic activity. The study also found that the addition of exogenous D-glucose and D-sucrose could significantly inhibit the hemolytic activity of Melittin. Our data provided an important theoretical basis for reducing the hemolytic activity of antimicrobial peptides and promoting their drug application.

References:

[1] Dathe M,Wieprecht T. Structural features of helical antimicrobial peptides:their potential to modulate activity on model membranes and biological cells[J]. Biochim Biophys Acta,1999,1 462(1/2):71-87.
[2]Cao L,Dai C,Li Z,et al. Antibacterial activity and mechanism of a scorpion venom peptide derivative in vitro and in vivo[J]. PLoS One,2012,7(7):e40135.
[3]Schweizer F. Cationic amphiphilic peptides with cancer-selective toxicity[J]. Eur J Pharmacol,2009,625(1/2/3):190-194.
[4]Han Y Y,Liu H Y,Han D J,et al. Role of glycosylation in the anticancer activity of antibacterial peptides against breast cancer cells[J]. Biochem Pharmacol,2013,86(9):1 254-1 262.
[5]Dennison S R,Harris F,Phoenix D A. The interactions of aurein 1.2 with cancer cell membranes[J]. Biophys Chem,2007,127(1/2):78-83.
[6]Lee H S,Park C B,Kim J M,et al. Mechanism of anticancer activity of buforin IIb,a histone H2A-derived peptide[J]. Cancer Lett,2008,271(1):47-55.
[7]Shai Y. Mechanism of the binding,insertion and destabilization of phospholipid bilayer membranes by alpha-helical antimicrobial and cell non-selective membrane-lytic peptides[J]. Biochim Biophys Acta,1999,1 462(1/2):55-70.
[8]Raghuraman H,Chattopadhyay A. Organization and dynamics of melittin in environments of graded hydration:a fluorescence approach[J]. Langmuir,2003,19:10 332-10 341.
[9]Raghuraman H,Chattopadhyay A. Interaction of melittin with membrane cholesterol:a fluorescence approach[J]. Biophys J,2004,87(4):2 419-2 432.
[10]Heinen T E,da Veiga A B. Arthropod venoms and cancer[J]. Toxicon,2011,57(4):497-511.
[11]Moon D O,Park S Y,Choi Y H,et al. Melittin induces Bcl-2 and caspase-3-dependent apoptosis through downregulation of Akt phosphorylation in human leukemic U937 cells[J]. Toxicon,2008,51(1):112-120.
[12]Park J H,Jeong Y J,Park K K,et al. Melittin suppresses PMA-induced tumor cell invasion by inhibiting NF-κB and AP-1-dependent MMP-9 expression[J]. Mol Cells,2010,29(2):209-215.
[13]Liu S,Yu M,He Y,et al. Melittin prevents liver cancer cell metastasis through inhibition of the Rac1-dependent pathway[J]. Hepatology,2008,47(6):1 964-1 973.
[14]Dathe M,Wieprecht T. Structural features of helical antimicrobial peptides:their potential to modulate activity on model membranes and biological cells[J]. Biochim Biophys Acta,1999,1 462(1/2):71-87.
[15]Weaver A J,Kemple M D,Brauner J W,et al. Fluorescence,CD,attenuated total reflectance(ATR)FTIR,and 13C NMR characterization of the structure and dynamics of synthetic melittin and melittin analogues in lipid environments[J]. Biochemistry,1992,31(5):1 301-1 313.
[16]Pérez-Payá E,Houghten R A,Blondelle S E. The role of amphipathicity in the folding,self-association and biological activity of multiple subunit small proteins[J]. J Biol Chem,1995,270(3):1 048-1 056.
[17]Asthana N,Yadav S P,Ghosh J K. Dissection of antibacterial and toxic activity of melittin:a leucine zipper motif plays a crucial role in determining its hemolytic activity but not antibacterial activity[J]. J Biol Chem,2004,279(53):55 042-55 050.
[18]Chen Y Q,Min C,Sang M,et al. A cationic amphiphilic peptide ABP-CM4 exhibits selective cytotoxicity against leukemia cells[J]. Peptides,2010,31:1 504-1 510.
[19]Chung J J,Ratnapala L A,Cooke I M,et al. Partial purification and characterization of a hemolysin(CAH1)from Hawaiian box jellyfish(Carybdea alata)venom[J]. Toxicon,2001,39(7):981-990.
[20]Marcotte I,Wegener K L,Lam Y H,et al. Interaction of antimicrobial peptides from Australian amphibians with lipid membranes[J]. Chem Phys Lipids,2003,122(1/2):107-120.
[21]Yeagle P L. Cholesterol and the cell membrane[J]. Biochim Biophys Acta,1985,822(3/4):267-287.
[22]Simons K,Ikonen E. How cells handle cholesterol[J]. Science,2000,290(5 497):1 721-1 726.
[23]Maher S,McClean S. Melittin exhibits necrotic cytotoxicity in gastrointestinal cells which is attenuated by cholesterol[J]. Biochem Pharmacol,2008,75(5):1 104-1 114.
[24]Raghuraman H,Chattopadhyay A. Cholesterol inhibits the lytic activity of melittin in erythrocytes[J]. Chem Phys Lipids,2005,134(2):183-189.
[25]Cassera M B,Silber A M,Gennaro A M. Differential effects of cholesterol on acyl chain order in erythrocyte membranes as a function of depth from the surface. An electron paramagnetic resonance(EPR)spin label study[J]. Biophys Chem,2002,99(2):117-127.

Memo

Memo:
-
Last Update: 2015-06-30