Membrane bound monomer of Staphylococcal alpha-hemolysin induces caspase activation and apoptotic cell death despite initiation of membrane repair pathway.
BACKGROUND
Wild type Staphylococcal alpha-hemolysin (alpha-HL) assembly on target mammalian cells usually results in necrotic form of cell death; however, caspase activation also occurs. The pathways of caspase activation due to binding/partial assembly by alpha-HL are unknown till date.


RESULTS
Cells treated with H35N (a mutant of alpha-HL that remains as membrane bound monomer), have been shown to accumulate hypodiploid nuclei, activate caspases and induce intrinsic mitochondrial apoptotic pathway. We have earlier shown that the binding and assembly of alpha-HL requires functional form of Caveolin-1 which is an integral part of caveolae. In this report, we show that the caveolae of mammalian cells, which undergo a continuous cycle of 'kiss and run' dynamics with the plasma membrane, have become immobile upon the binding of the monomer. The cells treated with H35N were unable to recover despite activation of membrane repair mechanism involving caspase-1 dependent activation of sterol regulatory element binding protein-1.


CONCLUSIONS
This is for the first time we show the range of cellular changes and responses that take place immediately after the binding of the monomeric form of staphylococcal alpha-hemolysin.
Srivastava
Saumya S
SS
National Centre for Cell Science, University of Pune Campus, Pune, India.
Pany
Satyabrata
S
Sneh
Amita
A
Ahmed
Neesar
N
Rahman
Aejazur
A
Musti
Krishnasastry V
KV
D017209:Apoptosis / Q000502:physiology*; D001427:Bacterial Toxins; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism*; D051242:Caveolin 1 / Q000502:physiology; D002460:Cell Line; D004789:Enzyme Activation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006460:Hemolysin Proteins / Q000502:physiology*; D006801:Humans; D006868:Hydrolysis; D008565:Membrane Proteins / Q000502:physiology*; D010718:Phosphatidylserines / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
D001427:Bacterial Toxins; D051242:Caveolin 1; D006460:Hemolysin Proteins; D008565:Membrane Proteins; D010718:Phosphatidylserines; C021091:staphylococcal alpha-toxin; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases