ABSTRACTS – ORAL PRESENTATIONS - AMCA, spol. s r.o.

28. S-ADENOSYLHOMOCYSTEINE HYDROLASE REGULATES C2-CERAMIDE INDUCED
CELL DEATH VIA INHIBITION OF THE INDUCTION OF THE INTRINSIC APOPTOTIC
PATHWAY
Roman Hudec 1,3,* , Kozo Hamada 1,2 , Hideaki Ando 1,2 and Katsuhiko Mikoshiba 1,2
1
Laboratory for Developmental Neurobiology, Brain Science Institute, RIKEN, 2-1
Hirosawa, Wako-shi, Saitama 351-0198, Japan
2
Calcium Oscillation Project, ICORP-SORST, Japan Science and Technology Agency (JST),
4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan
3
Institute of Biochemistry, Nutrition and Health Protection, Department of Biochemistry
and Microbiology, Faculty of Chemical and Food Technology, Slovak University of
Technology, Radlinskeho 9, 812 37 Bratislava, Slovak Republic
*roman.hudec@stuba.sk
S-adenosylhomocysteine hydrolase (SAHH) is the rate limited enzyme of the global
S-adenosylmethionin (SAM) dependent transmethylation of various biological substrates.
Here we report, that SAHH and in particular the SAHH enzymatic activity, is essential for
the C2-ceramide induced apoptosis. SAHH knock down by the specific siRNA, disabled
the C2-ceramide induced methylation of the catalytic subunit of protein phosphatase 2A
(PP2Ac) and therefore its activation. Such negative regulation led to inhibition of the C2-
ceramide induced apoptosis via mitochondrial intrinsic pathway. The opposite situation
has been observed by the transient transfection with the plasmid carried SAHH coding
sequence. Introduced SAHH protein caused augmentation of the endogenous SAHH
activity and subsequently caused elevation of the C2-ceramide induced apoptosis level.
SAHH protein levels are in general low in the neoplastic tissues; establishment or
reestablishment of its physiological level might be beneficial for the chemotherapy
successfulness, since many of currently used chemotherapeutics act also via mechanisms
involving the elevation of the endogenous ceramide levels and apoptosis induction.
Acknowledgements
This work was supported by grants from the Japan Society for the Promotion of Science
(JSPS), the Ministry of Education, Science, Sports and Culture of Japan to K.M (20220007),
and ICORP-SORST of JST. R.H. was a JSPS postdoctoral fellow.
Analytical Cytometry VII 53