Cystatin C expression in ischemic white matter lesions
Department of Internal Medicine III, University Hospital, Shimane University, Izumo, Japan. Acta Neurologica Scandinavica
(Impact Factor: 2.4).
07/2008; 118(1):60-7. DOI: 10.1111/j.1600-0404.2007.00984.x
To study the involvement of cystatin C in the progression of ischemic white matter lesions (WMLs).
Cystatin C levels in the cerebrospinal fluid (CSF) of patients with cerebrovascular disease, and also in primary and established human neural cell cultures were investigated. For pathologic analysis, cystatin C immunoreactivity was investigated in the white matter of patients with severe WMLs, mild WMLs or controls.
Cystatin C levels in the CSF of patients with Fazekas WML grade 3 [14 with hypertension; W/HT(+) and nine without hypertension; W/HT(-)] were lower than those in 38 patients with grade 0-1 (P = 0.0022 and P < 0.0001 respectively). Immunohistochemical study showed that the cystatin C immunoreactivity was found in astrocytes, and the number of astrocytes in the white matter in the severe WML group was decreased when compared with that in controls (P = 0.0027) and in the mild WML group (P = 0.0024). In human neural cell cultures, treatments with thrombin, matrix metalloproteinases and interleukin 1 beta increased the expression of cystatin C mRNA in human astrocytes and hybrid neurons, but an enzyme-linked immunosorbent assay revealed that only thrombin significantly increased the production and secretion of cystatin C in astrocytes.
These results suggest that low levels of CSF cystatin C in ischemic WMLs might be due to the decreased number of astrocytes that secrete cystatin C in response to the stimuli of proteases and inflammatory cytokines.
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- "Some experimental studies examined the vasoconstrictive effect of NPY (Abel et al., 1988; Uneyama et al., 1995) and in some clinical studies on SAH patients, the relation between the NPY levels in CSF and vasoconstriction (Schebesch et al., 2011; Juul et al., 1990;) and cognitive functions (Uski et al., 2000) were examined. Cystatin C is a sistein protease inhibitor, which takes part in the regulation of a local inflammation (Umegae et al., 2008). Most of the cystatin C is produced by nucleated cells and then, after glomerular filtration, it is catabolized by renal tubular cells (Grubb, 1992). "
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ABSTRACT: The aim of this study was to investigate the changes in the levels of cystatin C, which protects neurodegeneration in the central nervous system with the inhibition of cysteine protease and by inducing autophagy in the pathogenesis of cerebral vasospasm and levels of vasoconstrictive neuropeptid Y (NPY) in the brain tissue homogenates of rat model of subarachnoid hemorrhage (SAH). Three experimental groups were used: Day 2 and Day 7 groups after SAH, and also a control group. There were seven Wistar albino rats in each group. SAH was accomplished by transclival basilar artery puncture. Rat cystatin C, rat NPY were determined with ELISA in brain tissue homogenates. Day 2 group showed significantly enhanced cystatin C values in comparision with the control group (P=0.048). NPY levels between the Day 2 and Day 7 groups and the control groups were not significantly different (P=0.315). In histopathological examination, there was less neuronal loss in the Day 2 group than in the Day 7 group. Regarding our results, it would be more valuable to measure NPY levels in specific brain areas. The increased cystatin C levels on the second day after SAH is probably a pathophysiologic mechanism to organize protease activity.
Acta biochimica Polonica 12/2014; 61(4). · 1.15 Impact Factor
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ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective damage of motor
neurons in the brain and spinal cord. The aim of the current study was to reveal new specific markers of neurodegeneration
in the cerebrospinal fluid (CSF) of ALS patients. We measured the activities of substances that modulate the activity of cysteine
proteases (calpain, caspase, and cathepsin B) in the CSF of ALS patients. The CSF of ALS patients, in contrast to the CSF
of patients with multiple sclerosis, inhibits calpain and cathepsin B significantly more strongly, as compared to the control
CSF. The LDH activity and the concentration of neuron-specific enolase (NSE) in the CSF of control patients and ALS patients
did not differ. The concentration of neurofilament heavy chains in the CSF was significantly higher in the ALS patients as
compared to the control group. The albumin index increased in 50% of all ALS patients. We also have shown a correlation between
the cathepsin inhibitor activity, the concentration of neurofilament heavy chains, and the albumin index and the clinical
findings of the disease. According to our data, the concentration of neurofilament heavy chains is a sensitive marker of neurodegenerative
process during ALS. An increase in the CSF inhibiting activity with respect to cathepsin B and calpain is specific for ALS
and may confirm the role of an imbalance of proteolytic systems in the pathogenesis of this disease.
Neurochemical Journal 06/2009; 3(2):133-138. DOI:10.1134/S1819712409020093 · 0.30 Impact Factor
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ABSTRACT: Recent studies have shown that kidney dysfunction is associated with cerebral small vessel disease (SVD). Although creatinine-based estimating equations have been used as the standard measure for the evaluation of kidney function, the accuracy of these is limited in the elderly because of muscle mass decrease with aging. Cystatin C is a more useful measurement than creatinine-based estimating equations for evaluating kidney function, however, the relationship amongst cystatin C, cognitive dysfunction, and cerebral SVD has not been fully examined in community-based elderly.
We performed a cross-sectional study using MRI to determine the relationship amongst cystatin C, cognitive function, and cerebral SVD in a total of 604 community-based Japanese elderly.
In this study, subjects with higher cystatin C levels tended to have more lacunas and higher grades of white matter lesions. Although a decline of the Mini-Mental State Examination (MMSE) scores was associated with SVD-related lesions, the relationship between the tertiles of cystatin C and mean MMSE scores was not statistically significant. In the logistic regression analysis, the association between cystatin C and SVD-related lesions was statistically significant, even after adjustment for conventional risk factors and high-sensitivity C-reactive protein. Furthermore, subjects with higher cystatin C levels accompanied with albuminuria had a greater risk for the presence of subclinical cerebral SVD than those with lower cystatin C levels without albuminuria.
The present study suggests that there is a close relationship between cystatin C and subclinical cerebral SVD, independently of conventional risk factors, in community-based elderly.
European Journal of Neurology 10/2009; 17(3):383-90. DOI:10.1111/j.1468-1331.2009.02809.x · 4.06 Impact Factor
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