liiiMIIIfl~UDliiiMIII~U - Biblioteca de la Universidad Complutense ...
liiiMIIIfl~UDliiiMIII~U - Biblioteca de la Universidad Complutense ...
liiiMIIIfl~UDliiiMIII~U - Biblioteca de la Universidad Complutense ...
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Vol. 224. No. 3, 1996 . BIOCHEMICAL. ANt> BIOPHYSICAL RESEARCH COMMUNYCATYONS<br />
phosphatase 2A in dic control of CPT-! activity. !nterestingly, taxol also prevented dic<br />
tautomycin-induced activation of CPT-I.<br />
DISCUSSION<br />
Severa! smdies ~erfonnedby aur group using digitonin-penneabilized hepatocytes lcd to<br />
te suggestion that a mechanism of phosphory<strong>la</strong>úon-<strong>de</strong>phosphory<strong>la</strong>tion miglxt be involúed in<br />
te short-tenn control ofmí liver CPT-I acúviíy (reviewed un ref. 3). However, furíher researcb<br />
showed taí te incitase in CPT-I acíiviíy observed ¡ix QA-treated hepatocytes was not chic<br />
to direcí phosphory<strong>la</strong>íion of te CFI’-! enzyme, buí may involve interacíions beíwecn te<br />
mitochondrial outer membrane mrd exíra-mitochondrial, non-diffusiblc ccli componenís (6).<br />
Data on te effects of tao! preseníed lix te prcsentrepon indicate that te extra-mitochondrial<br />
cd components poíentiaily involved lix tite short-term control of CPT-I activity might resi<strong>de</strong><br />
¡ix tite cytoskeleíon. lix addition, te data on te síinxu<strong>la</strong>tion of CPT-! by OA mrd tautornycin<br />
suggest thai protein phospbatase 1 is more imporíaní tan protein pitospitatase 2A lix dic sitorííerm<br />
control of CP’T-I. Titis is lix agreement wit tite observation thai pitospitatase 1 seems to<br />
be tite ¡naln proicin pitospitatase involved ¡ix te regu<strong>la</strong>tion of tite phosphory<strong>la</strong>tion state ofte<br />
cyíoskeleíon, mrd ¡ix mm in tite control of cytoskeletal integrity (21,24).<br />
Thc namure of tite putative cyíoskeletal componení(s) tlxaí might be involved lix controlling<br />
CPT-I activity is still unknown. A firsm possibility could be thai tite control of CFI?-! activity<br />
by tose potential interactions between mimochondria mrd te cytoskeleton merely reflected a<br />
physicail pitenomenon, Le. CPT-I acmivity might be <strong>de</strong>pendcnt on mitochondrial shapc, stretcix-<br />
¡ng or cantraction of dxc ¡nimochondrial outer membrane, etc. (cf ref. 7). A second possibility<br />
couild be thai modu<strong>la</strong>don of CPT-I activimy involved te specific inmeraction between CPT-I<br />
sud regu<strong>la</strong>tory cymoskeletal promein(s). Titis notion is supported by te obscn’ation thai te mere<br />
disruption of microtubules by 2-methoxy 5-(2,3,4--¡rimethoxyphenyl) 2,4,6-cycloheptatrien-1one<br />
or coichicine or te mere disruption of actin microfi<strong>la</strong>menís by cytocha<strong>la</strong>sin B does<br />
noí affect CPT-I activimy (unpublished work). QA mrd otiter pitospitatase inhibitors produce<br />
hyperphosphory<strong>la</strong>tion mrd consequently disruption of microtubules, actin microfi<strong>la</strong>mcnts mrd<br />
inmennediame fi<strong>la</strong>ments in several ccli Unes, includ¡ng hepamocytes (21,25,26)- Whether diese<br />
cymoskeletal changes are re<strong>la</strong>ted to te cifecís of QA on hepatic CPT-I activity is as yet mr<br />
open question.<br />
AOKNOWLEDGMENTS<br />
flese ¡avestigaúons were supparred ¡a pan by te Nerher<strong>la</strong>nds Faundarian far Chemical Reseaxch (SON) with<br />
financial aid ftam dic Nether<strong>la</strong>nds Organizarion for Scienrific Researcb (NWO).<br />
REFERENCES<br />
1. McGariy. 1. D.. Waekje. Kl E, Kuwajima, Ml. and Fasrer, D. W. . 0. (1995) Eur. ¿ Biochem. 230, 17—24.<br />
14. Guzmán, M., Ve<strong>la</strong>sco, G-, Castro, 3., md Zammit, V. A. (1994) FEBS Lar. 344,239-241.<br />
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