High plasma cyst(e)ine level may indicate poor clinical outcome in patients with acute stroke: possible involvement of hydrogen sulfide.
Cysteine is known to cause neuronal cell death and has been reported to be elevated in brain ischemia, but it has not been studied in clinical stroke. In this study, we correlated plasma levels of cyst(e)ine with long-term clinical outcome at 3 months in acute stroke. Patients were classified into 3 groups at 3 months as follows: good outcome (Rankin 0-1, n = 11), poor outcome (Rankin 2-5, n = 20), and dead (n = 5). Their plasma cyst(e)ine levels within 24 hours of stroke onset were 61 +/- 12, 67 +/- 9, and 82 +/- 14 micromol/L (standard deviation), respectively. The correlation between early plasma cyst(e)ine levels and long-term clinical outcome assessed at 3 months is significant with p < 0.001. None of the other 4 amino acids studied showed any significant correlation. Cyst(e)ine was also significantly elevated in patients who had early stroke deterioration (p < 0.02). Dose-dependent administration of cysteine increased the infarct volume by approximately 30% in a rat stroke model. This effect of cysteine was abolished by aminooxyacetic acid, an inhibitor of the enzyme cystathionine beta-synthase that converts cysteine to hydrogen sulfide (H2S), indicating that this novel neuromodulator may be acting as a mediator of ischemic brain damage. Raised plasma cyst(e)ine in patients with stroke may reflect increased production of H2S in the brain and thus predispose to poor outcome in clinical stroke. Inhibition of H2S formation may therefore be a novel approach in acute stroke therapy.
Wong
Peter T H
PT
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Qu
Kun
K
Chimon
Ghislain N
GN
Seah
Alvin B H
AB
Chang
Hui Meng
HM
Wong
Meng Cheong
MC
Ng
Yee Kong
YK
Rumpel
Helmut
H
Halliwell
Barry
B
Chen
Christopher P L H
CP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000097:blood; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003545:Cysteine / Q000008:administration & dosage / Q000097:blood*; D003553:Cystine / Q000008:administration & dosage / Q000097:blood*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology
D000596:Amino Acids; D003553:Cystine; D003545:Cysteine; D006862:Hydrogen Sulfide