The possible role of lysosomal enzymes in the pathogenesis of hypertensive cerebral lesions in spontaneously hypertensive rats

Chue, Chin-Hui; Yukioka, Naoya; Yamada, Eiji; Hazama, Fumitada

doi:10.1007/bf00334448

Cited by 12 publications

(5 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Age-related increase in calpain activity may be associated with cataract formation in the lens (David et al, 1994). Cathepsin B activity in brain also increases with age in the rat (Chue et al, 1993). As already mentioned, the changes in enzyme content do not parallel the changes in enzyme activity in the living organism.…”

Section: Discussionmentioning

confidence: 76%

Changes in Brain Protease Activity in Aging

Benuck

Banay‐Schwartz

DeGuzman

et al. 1996

Journal of Neurochemistry

View full text Add to dashboard Cite

We measured changes in protease activity with aging, conducting assays of cathepsin D and calpain II activities and the rate of degradation of cytoskeletal proteins, preparing the enzymes and substrates from young and aged brains. Calpain preparations added to the young and to the aged substrates were standardized with casein as substrate so that age‐related changes in calpain specificity and substrate susceptibility were measured. Several age‐related differences were observed in substrate susceptibility and in enzyme activity. With respect to substrate, the neurofilament protein from young animals was somewhat more susceptible to calpain action than that from older animals. With respect to enzyme activity, calpain from aged brain cleaved neurofilament protein at a faster rate than did calpain from young. With neurofilaments, the most rapid breakdown usually occurred when enzyme from aged tissue was incubated with substrate from young. Kidney enzyme of aged rats incubated with neurofilament substrate of aged rats resulted in a more rapid breakdown than enzyme of young kidney incubated with substrate of young. The age dependence of tubulin breakdown was somewhat different from that of neurofilament breakdown. The most rapid breakdown usually occurred when using enzyme from young with tubulin from young. Incubation of neurofilament protein or tubulin with cathepsin D did not reveal any differences with aging. These studies suggest that an increase in enzyme activity observed previously during aging may also include changes in the properties of the enzyme (substrate specificity) and/or in the properties of their endogenous substrates (susceptibility to breakdown).

show abstract

Section: Discussionmentioning

confidence: 76%

Changes in Brain Protease Activity in Aging

Benuck

Banay‐Schwartz

DeGuzman

et al. 1996

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…Tissue damage in SHRSP seemed mostly to occur in the frontal cortex and basal ganglia (20–22), usually within the territory of the MCA/anterior cerebral artery, MCA/PCA borderzones (23) and the lenticulostriate arteries (20). Cerebral pathology included cortical infarcts, enlarged perivascular spaces (24, 25), white matter damage, microinfarcts and microaneurysms (3, 20, 26, 27). Studies that examined lesion distribution found most lesions occurred in the basal ganglia (20).…”

Section: Resultsmentioning

confidence: 99%

Is the Spontaneously Hypertensive Stroke Prone Rat a Pertinent Model of Sub Cortical Ischemic Stroke? A Systematic Review

Bailey

Smith

Sudlow

et al. 2011

International Journal of Stroke

102

View full text Add to dashboard Cite

The spontaneously hypertensive stroke prone rat is best known as an inducible model of large artery stroke. Spontaneous strokes and stroke propensity in the spontaneously hypertensive stroke prone rat are less well characterized; however, could be relevant to human lacunar stroke. We systematically reviewed the literature to assess the brain tissue and small vessel pathology underlying the spontaneous strokes of the spontaneously hypertensive stroke prone rat. We searched systematically three online databases from 1970 to May 2010; excluded duplicates, reviews, and articles describing the consequences of induced middle cerebral artery occlusion or noncerebral pathology; and recorded data describing brain region and the vessels examined, number of animals, age, dietary salt intake, vascular and tissue abnormalities. Among 102 relevant studies, animals sacrificed after developing stroke-like symptoms displayed arteriolar wall thickening, subcortical lesions, enlarged perivascular spaces and cortical infarcts and hemorrhages. Histopathology, proteomics and imaging studies suggested that the changes not due simply to hypertension. There may be susceptibility to endothelial permeability increase that precedes arteriolar wall thickening, degeneration and perivascular tissue changes; systemic inflammation may also precede cerebrovascular changes. There were very few data on venules or tissue changes before hypertension. The spontaneously hypertensive stroke prone rat shows similar features to human lacunar stroke and may be a good spontaneous model of this complex human disorder. Further studies should focus on structural changes at early ages and genetics to identify factors that predispose to vascular and brain damage.

show abstract

“…Histochemical study showed cathepsin B to be distributed more heavily in the cells in edematous cortex and in degenerating subcortical white matter. 10 Cathepsin B activity in the brain of spontaneously hypertensive rats also increased with advancing age coincident with the progressing extent of the vascular lesions. 10 Immunohistochemical studies in patients diagnosed with early-onset Alzheimer's disease documented increased expression of cathepsins B and D within neurons, suggesting that these enzymes are involved in the degenerative pathological process.…”

Section: Discussionmentioning

confidence: 96%

“…10 Cathepsin B activity in the brain of spontaneously hypertensive rats also increased with advancing age coincident with the progressing extent of the vascular lesions. 10 Immunohistochemical studies in patients diagnosed with early-onset Alzheimer's disease documented increased expression of cathepsins B and D within neurons, suggesting that these enzymes are involved in the degenerative pathological process. 7,25 In our study the expression of cathepsin B was increased within ischemic neurons, but not in astrocytes or microglial cells, within 2 hours of reperfusion after a 2-hour MCA occlusion.…”

Section: Discussionmentioning

confidence: 96%

Cathepsin B and middle cerebral artery occlusion in the rat

Seyfried¹,

Han²,

Zheng³

et al. 1997

Journal of Neurosurgery

View full text Add to dashboard Cite

Lysosomal proteases, although tightly regulated under physiological conditions, are known to contribute to cell injury after various forms of tissue ischemia have occurred. Because cathepsin B is a prominent lysosomal protease found in brain parenchyma, the authors hypothesized that it may contribute to neuronal cell death after focal cerebral ischemia. The authors measured the expression and spatial distribution of cathepsin B within the ischemic brain in 43 animals by means of immunohistochemical analysis in a rat model of transient middle cerebral artery (MCA) occlusion. Cathepsin B activity was also measured within specific ischemic brain regions by using an in vitro assay (22 animals). In addition, the authors tested the therapeutic effect of preischemic intraventricular administration of stefin A, a cysteine protease inhibitor, on the volume of cerebral infarction after transient MCA occlusion (15 animals). Increased cathepsin B immunoreactivity was detected exclusively within the ischemic neurons after 2 hours of reperfusion following a 2-hour MCA occlusion. Cathepsin B immunolocalization in the ischemic region decreased by 24 hours of reperfusion, but then increased by 48 hours of reperfusion because the infarct was infiltrated by inflammatory cells. Increased immunolocalization of cathepsin B in the inflammatory cells located in the necrotic infarct core continued through 7 days of reperfusion. Cathepsin B enzymatic activity was significantly increased in the ischemic tissue at 2, 8, and 48 hours, but not at 24 hours of reperfusion after 2 hours of MCA occlusion. Continuous intraventricular infusion of stefin A, before 2 hours of MCA occlusion (15 animals), significantly reduced infarct volume compared with control animals (12 animals): the percentage of hemispheric infarct volume was 20+/-3.9 compared with 33+/-3.5 (standard error of the mean; p = 0.025). These data indicate that neuronal cathepsin B undergoes increased expression and activation within 2 hours of reperfusion after a 2-hour MCA occlusion and may be a mechanism contributing to neuronal cell death. Intraventricular infusion of stefin A, an inhibitor of cathepsin B, significantly reduces cerebral infarct volume in rats.

show abstract

The possible role of lysosomal enzymes in the pathogenesis of hypertensive cerebral lesions in spontaneously hypertensive rats

Cited by 12 publications

References 28 publications

Changes in Brain Protease Activity in Aging

Changes in Brain Protease Activity in Aging

Is the Spontaneously Hypertensive Stroke Prone Rat a Pertinent Model of Sub Cortical Ischemic Stroke? A Systematic Review

Cathepsin B and middle cerebral artery occlusion in the rat

Contact Info

Product

Resources

About