Cystine Exodus From Leukocyte Granular Fractions Is Stimulated by Atp at Sub-Saturating Cystine Levels

Abstract

M ,R e n n e r t .Univ. O k l a . , D e p t . P e d i a t r . , O k l a . C i t y .T h e X -l i n k e d mouse m u t a n t b r i n d l e d is a m o d e l f o r Menkes s y n d r o m e . I n y o u n g h e m i z y g o t e s , r e d u c e d l i v e r a n d b r a i n c o p p e r c o n c e n t r a - t i o n s are a s s o c i a t e d w i t h n e u r o l o g i c d y s f u n c t i o n .I n f e t u s e s c o p p e r c o n c e n t r a t i o n s i n p l a c e n t a a n d k i d n e y a r e h i g h e r i n b r i n d l e d t h a n c o n t r o l s w h i l e t h o s e i n l i v e r a n d c a r c a s s are lower.To t r e a t t h e c o p p e r d e f i c i e n c y i n b r i n d l e d y o u n g , h e t e r o z y g o t e s w e r e i n j e c t e d a t 1 6 o r 1 8 d a y s g e s t a t i o n w i t h c o p p e r , 6 m c g / g / d o s e , a s c u p r i c c h l o r i d e , 1 8 a n d 6 h o u r s b e f o r e s a c r i f i c e .P l a c e n t a l , c a r c a s s , a n d h e p a t i c c o p p e r c o n c e n t r a t i o n s i n b r i n d l e d f e t u s e s i n c r e a s e d ( p > 0 . 0 0 6 ) .I n j e c t i o n o f m e t h y l p r e d n i s o l o n e , 5 mcg/g, 2 0 h o u r s b e f o r e t h e c o p p e r , t o i n c r e a s e f e t a l h e p a t l c copper s t o r a g e t h r o u g h m e t a l l o t h i o n e i n i n d u c t i o n , r e s u l t e d o n l y i n f u r t h e r i n c r e a s e i n t h e c a r c a s s c o p p e r c o n c e n t r a t i o n s .T h e s e d a t a s u g g e s t : p l a c e n t a l c o p p e r t r a n s p o r t i n b r i n d l e d f e t u s e s i s i m p a i r e d ; h e p a t i c c o p p e r b i n d i n g c a p a c i t y o f c o n t r o l a n d b r i n d l e d f e t u s e s is l i m i t e d a n d c a n n o t b e a u g m e n t e d b y p r e t r e a t m e n t w i t h m e t h y l p r e d n i s o l o n e ; e x t r a -h e p a t i c W e have been using chromosome heteromorphisms and r e s t r i ct i o n fragment length polymorphisms (RFLPs) t o i n v e s t i g a t e t h e mechanism of o r i g i n of trisorny 13, and t h e possible association between e r r o r s of recombination and t h e non-disjunctional event leading t o trisomy. To date, we have studied 33 liveborn o r spontaneously aborted trisomy 13 conceptions. By combining analysis of chromosome heteromorphisms with analysis'of seven probes detecting chromosome 1 3 RFLPs, we have been able t o determine t h e parental o r i g i n of 23 cases, with 20 being maternal and 3 paternal i n o r i g i n .I n eight cases i n which we have both cytogenetic and molecular information, we can make inferences regarding recombination i n t h e two non-disjoined chromosomes. We have evidence f o r recombination i n two of t h r e e cases i n which the e x t r a 13 originated i n maternal meiosis I and i n both instances t h i s observation i s based on r e s u l t s from s e v e r a l probes. This suggests t h a t absence of recombination due t o p a i r i n g f a i l u r e is unlikely t o be an important mechanism i n t h e genesis of human trisomy. Furthermore, analysis of recombinatio...