Allicin disrupts the cell's electrochemical potential and induces apoptosis in yeast.
The volatile substance allicin gives crushed garlic (Allium sativum) its characteristic odor and is a pro-oxidant that undergoes thiol-disulfide exchange reactions with -SH groups in proteins and glutathione. The antimicrobial activity of allicin is suspected to be due to the oxidative inactivation of essential thiol-containing enzymes. We investigated the hypothesis that at threshold inhibitory levels allicin can shunt yeast cells into apoptosis by altering their overall redox status. Yeast cells were treated either with chemically synthesized, pure allicin or with allicin in garlic juice. Allicin-dependent cell oxidation was demonstrated with a redox-sensitive GFP construct and the shift in cellular electrochemical potential (E(hc)) from less than -215 to -181mV was calculated using the Nernst equation after the glutathione/glutathione disulfide couple (2GSH/GSSG) in the cell was quantified. Caspase activation occurred after allicin treatment, and yeast expressing a human antiapoptotic Bcl-XL construct was rendered more resistant to allicin. Also, a yeast apoptosis-inducing factor deletion mutant was more resistant to allicin than wild-type cells. We conclude that allicin in garlic juice can activate apoptosis in yeast cells through its oxidizing properties and that this presents an alternative cell-killing mechanism to the previously proposed specific oxidative inactivation of essential enzymes.
Gruhlke
Martin C H
MC
Department of Plant Physiology (Bio III), RWTH Aachen University, Aachen, Germany.
Portz
Daniela
D
Stitz
Michael
M
Anwar
Awais
A
Schneider
Thomas
T
Jacob
Claus
C
Schlaich
Nikolaus L
NL
Slusarenko
Alan J
AJ
D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D004220:Disulfides; D004789:Enzyme Activation; D005737:Garlic; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D050296:Microbial Viability / Q000187:drug effects; D010084:Oxidation-Reduction; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects; D013441:Sulfinic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D051020:bcl-X Protein / Q000378:metabolism
D000935:Antifungal Agents; D004220:Disulfides; D010936:Plant Extracts; D011994:Recombinant Proteins; D013441:Sulfinic Acids; D051020:bcl-X Protein; D049452:Green Fluorescent Proteins; C006452:allicin; D020169:Caspases; D005978:Glutathione; D019803:Glutathione Disulfide