The presence of an extractable substance in the CSF of humans with cerebral vasospasm after subarachnoid haemorrhage that correlates with phosphatase inhibition

被引:19
作者
Pyne, GJ
Cadoux-Hudson, TAD
Clark, JF
机构
[1] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England
[2] MRC, Ctr Collaborat, Vasc Res Grp, London NW7 1AD, England
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 2000年 / 1474卷 / 03期
基金
英国医学研究理事会;
关键词
vasospasm; vascular smooth muscle; relaxation; contraction;
D O I
10.1016/S0304-4165(00)00030-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The cellular events leading to cerebral vasospasm after subarachnoid haemorrhage are poorly understood, although an increase in smooth muscle myosin light chain phosphorylation has been observed. This study set out to determine if phosphatase inhibition may be involved in the pathological maintenance of tension observed during vasospasm. We found that 1 nM okadaic acid, a type 2A protein phosphatase inhibitor, elicited an increase in rate of O-2 consumption in the porcine carotid artery similar to that by cerebrospinal fluid (CSF) from vasospastic patients (CSFv, it = 5) (control 0.23 +/- 0.03, CSFv 0.84 +/- 0.16 and okadaic acid 0.85 +/- 0.02 mu mol min(-1) g dwt(-1)). It was also observed that phosphatase inhibition with 1 nM okadaic acid significantly slowed relaxation after a stretch in a similar fashion to CSFv haemorrhage. CSF from vasospastic subarachnoid haemorrhage patients, but not from those without vasospasm, contains an extractable substance which modulates myosin light chain phosphorylation in vitro. A phosphatase preparation obtained from the porcine carotid artery dephosphorylated 63 +/- 2% of the phosphorylated (MLC20) substrate in vitro, and non-vasospastic CSF treated enzyme dephosphorylated 60 +/- 2.6%. Okadaic acid inhibited phosphatase dephosphorylated only 7.5 +/- 1% of the substrate where CSFv treated enzyme dephosphorylated 22 +/- 2.8% of the substrate. We conclude that inhibition of smooth muscle phosphatase may be involved in the mechanisms associated with cerebral vasospasm after subarachnoid haemorrhage. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:283 / 290
页数:8
相关论文
共 52 条
[1]   THE CONTROL OF PROTEIN PHOSPHATASE-1 BY TARGETING SUBUNITS - THE MAJOR MYOSIN PHOSPHATASE IN AVIAN SMOOTH-MUSCLE IS A NOVEL FORM OF PROTEIN PHOSPHATASE-1 [J].
ALESSI, D ;
MACDOUGALL, LK ;
SOLA, MM ;
IKEBE, M ;
COHEN, P .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1992, 210 (03) :1023-1035
[2]   PROTEIN-PHOSPHORYLATION DURING THE CONTRACTION RELAXATION CONTRACTION CYCLE OF ARTERIAL SMOOTH-MUSCLE [J].
BARANY, M ;
POLYAK, E ;
BARANY, K .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1992, 294 (02) :571-578
[3]  
Barany M., 1996, BIOCH SMOOTH MUSCLE, P321
[4]   Vascular smooth muscle oxygen consumption is reversibly stimulated by sera from women with preeclampsia [J].
Bearchell, MC ;
Redman, CWG ;
Pyne, GJ ;
Cadoux-Hudson, T ;
Clark, JF .
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 1998, 179 (06) :1534-1538
[5]   EVIDENCE FOR PRESENCE OF A VASOACTIVE SUBSTANCE (POSSIBLY INVOLVED IN ETIOLOGY OF CEREBRAL ARTERIAL SPASM) IN CEREBROSPINAL-FLUID FROM PATIENTS WITH SUBARACHNOID HEMORRHAGE [J].
BOULLIN, DJ ;
MOHAN, J ;
GRAHAMESMITH, DG .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1976, 39 (08) :756-766
[7]   Intracellular calcium, myosin light chain phosphorylation, and contractile force in experimental cerebral vasospasm [J].
Butler, WE ;
Peterson, JW ;
Zervas, NT ;
Morgan, KG .
NEUROSURGERY, 1996, 38 (04) :781-787
[8]  
CADOUXHUDSON TAD, 1999, EMERGING THERAPEUTIC, V3, P439
[9]   AN IMPROVED PROCEDURE FOR IDENTIFYING AND QUANTITATING PROTEIN PHOSPHATASES IN MAMMALIAN-TISSUES [J].
COHEN, P ;
KLUMPP, S ;
SCHELLING, DL .
FEBS LETTERS, 1989, 250 (02) :596-600
[10]   MECHANISMS OF CEREBRAL VASOSPASM IN SUBARACHNOID HEMORRHAGE [J].
COOK, DA .
PHARMACOLOGY & THERAPEUTICS, 1995, 66 (02) :259-284