1,4-butanediyl-bismethanethiosulfonate (BMTS) induces apoptosis through reactive oxygen species-mediated mechanism.
Although methane sulfonate compounds are widely used for the protein modification for their selectivity of thiol groups in proteins, their intracellular signaling events have not yet been clearly documented. This study demonstrated the methane sulfonate chemical 1,4-butanediyl-bismethanethiosulfonate (BMTS)-induced cascades of signals that ultimately led to apoptosis of Jurkat cells. BMTS induced apoptosis through fragmentation of DNA, activation of caspase-9 and caspase-3, and downregulation of Bcl-2 protein with reduction of mitochondrial membrane potential. Moreover, BMTS intensely and transiently induced intracellular reactive oxygen species (ROS) production and ROS produced by BMTS was mediated through mitochondria. We also found that a reducing agent dithiothreitol (DTT) and an anti-oxidant N-acetyl cysteine (NAC) inhibited BMTS-mediated caspase-9 and -3 activation, ROS production and induction of Annexin V/propidium iodide double positive cells, suggesting the involvement of ROS in the apoptosis process. Therefore, this study further extends our understanding on the basic mechanism of redox-linked apoptosis induced by sulfhydryl-reactive chemicals.
Hossain
Khaled
K
Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi 6205, Bangladesh.
Kawamoto
Yoshiyuki
Y
Hamada
Masataka
M
Akhand
Anwarul A
AA
Yanagishita
Takeshi
T
Hoque
Md Ashraful
MA
Tsuboi
Hideo
H
Kato
Masashi
M
Nakashima
Izumi
I
D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004229:Dithiothreitol / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013886:Thiosulfonic Acids / Q000494:pharmacology*
C454105:1,4-butanediylbismethanethiosulfonate; D016166:Free Radical Scavengers; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D013886:Thiosulfonic Acids; D053148:Caspase 3; D053453:Caspase 9; D004229:Dithiothreitol; D000111:Acetylcysteine