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Vol. 224, No. 3, 1996 BIOafEMYCAL AND BIOPHYSYCAL RESEARCH COMMUNICAflONs
Taxol OA
TASIS 2
laxal Prevents Heparocyte Sbrinkage as WeII as Release of Lacrare Dehydrogenase
from Permeabilized Heparocytes
385 mOsm
medium
Wer weight:
D¡y weight
Lactare dehydrogenase
rerained in ceil ghasrs
3.93 t 0.07
(100) 6.5 t 1.1
367 t 0.03*
— -~- (93.4) 2.0 ± 0.3*
334 ±0.02
(100.3) 6.7 z 1.4
3.92 ~ 0.04
— .4- (99.7) 6.6 ~ 0.9
3.47 t 0.07w
— — + . (88.3) o-d.
3.86 ~ 0.08
+ — (98.2) n4.
Heparocytes were preincubared for 30 mía iii te absence ar ¡a te presence of 10 ¿M raxol, follawed by 15
addiional m¡a wxt ar withonr0.5 ~¿MQA ar 30 addiúanal mía iii hyperosmaúc mediuzn. men, pan of ¡he hepatacytes
was used ro determine ¡he wet ro dry cd weigbt rano. The percenhage as compared ra ¡acubañoas wi¡h no addinians
Ls sbawn ¡a parenteses. Ibe rest ofte celis was permeabiluzed wit ca. 40 pg digitaninimg prarein and ¡he pereentage
of lacrare debydrogenase rerained by ¡he permeabilized celis was determuned. Values correspond ra 4 separare beparaeyre
prepararians. ~P c 0.01 versus íncubadons wit no additions. n.d.: nar determuned.
effect of QA on CPT-I activity was mostly due to inhibiton of phosphatase 1 ar 2A, we
campared te effect of OA with that of tautomycin, wbich inhibits phosphatase 1 more
efficiently tan pliospliatase 2A (23). As shown in Fig- 2, tautomycin was quite more
potent lix stimulating hepatic CPT-I activity (50% of acúvation at 4 olA) titan OA (50%
activation at 18 nM), indicating tlxat protein phosphatase 1 is more important tan pratein
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