Progress in Drug Treatment for Renal Ischemic Reperfusion Injury / 中国药师

Renal ischemia reperfusion injury refers to the recovery failure of renal function induced by renal perfusion after ischemia,and resulting in a series of pathophysiological reactions.At present,there are no sovereign drugs for the treatment of renal ischemia reperfusion injury.Based on the pathophysiological characteristics of renal ischemia reperfusion injury and the latest research results at home and abroad,the article reviewed the research progress in the therapeutical drugs for renal ischemia reperfusion injury,including apoptotic protease inhibitors,P-selectin antagonists and antioxidants,which could provide reference for the effective intervention with the disease.

RoIes of Caspase Inhibitors in CochIear Hair CeIIs SurvivaI and Preventing Age-ReIated Hearing Loss / 听力学及言语疾病杂志

Objective In this study ,we investigated the apoptosis of hair cell in the cochlea of age -related hearing loss(AHL) generated by ENU mutagenesis ,and to study a pan caspase inhibitor (z-VAD -FMK) which is to protect the cochlea hair cells from hearing loss induced by age-related hearing loss(AHL) .Methods Through z-VAD-FMK intraperitoneal injection and round window membrane (RWM) drug were delivered into the Cdh23 nmf308 nmf/nmf mice 5(postnatal days 2 -32) inner ear .ResuIts The results showed that the nmf308 mice with progressive hair cell loss along a base to apex gradient with age-related hearing loss .The cochlear OHCs reduced from 5% ~10% at 1 month to 100% at 3 month in the basal region .Substantial amounts of TUNEL -positive OHCs nuclei appeared at 1 month age ,and activated caspase-3 labeling demonstrated that most OHCs appeared at 2 months age .These suggested that DNA single strand break was attributed primarily to apoptosis of cochlear le_sions ,whereas in the later stage of lesion ,the expansion led to activation of caspase-3 activity reduced with further progression of nuclear condensation in age-related hearing loss .ConcIusion The addition of a pan caspase inhibitor (z -VAD -FMK ) significantly protected the cochlea against the hair cell loss induced by apoptosis .Our study showed that aspase inhibitor ,Z-VAD-FMK appeared to play a prominent role in age-related hearing loss media_ted hair cell death loss induced by apoptosis .Our study showed that aspase inhibitor ,Z-VAD -FMK appeared to play a prominent role in age-related hearing loss mediated hair cell death .

The caspase-3 inhibitor (peptide Z-DEVD-FMK) affects the survival and function of platelets in platelet concentrate during storage

BACKGROUND: Although apoptosis occurs in nucleated cells, studies show that this event also occurs in some anucleated cells such as platelets. During storage of platelets, the viability of platelets decreased, storage lesions were observed, and cells underwent apoptosis. We investigated the effects of caspase-3 inhibitor on the survival and function of platelets after different periods of storage. METHODS: Platelet concentrates were obtained from the Iranian Blood Transfusion Organization in plastic blood bags. Caspase-3 inhibitor (Z-DEVD-FMK) was added to the bags. These bags along with control bags to which no inhibitor was added were stored in a shaking incubator at 22degrees C for 7 days. The effects of Z-DEVD-FMK on the functionality of platelets were analyzed by assessing their ability to bind to von Willebrand factor (vWF) and to aggregate in the presence of arachidonic acid and ristocetin. Cell survival was surveyed by MTT assay. RESULTS: At day 4 of storage, ristocetin-induced platelet aggregation was significantly higher in the inhibitor-treated (test) than in control samples; the difference was not significant at day 7. There was no significant difference in arachidonic acid-induced platelet aggregation between test and control samples. However, at day 7 of storage, the binding of platelets to vWF was significantly higher in test than in control samples. The MTT assay revealed significantly higher viability in test than in control samples at both days of study. CONCLUSION: Treatment of platelets with caspase-3 inhibitor could increase their functionality and survival.

The Function of SeMNPV IAP3 in Mammalian Cells / 中国病毒学·英文版

The baculoviral inhibitors of apoptosis play a significant role in infectivity and viral host-range, which make them potential candidates for the engineering and improvement of baculovirus insecticidal. The iap3 gene of Spodoptera exigua nucleopolyhedrovirus (SeMNPV), amplified by PCR, was 939 bp encoding IAP3. The PCR product was cloned into EcoR I/Bam H I of the plasmid pEGFP-C1. GFP was fused to the N-terminaus of IAP3 to study distribution in HEK293. It was observed that the plasmid expressing IAP3 significantly inhibited apoptosis induced by cisplatin in HEK293 cells. We conclude that the IAP3 of SeMNPV is functional in mammalian cells.

Activation of caspase-8 in 3-deazaadenosine-induced apoptosis of U-937 cells occurs downstream of caspase-3 and caspase-9 without Fas receptor-ligand interaction

3-Deazaadenosine (DZA), a cellular methylation blocker was reported to induce the caspase-3-like activities-dependent apoptosis in U-937 cells. In this study, we analyzed the activation pathway of the caspase cascade involved in the DZA-induced apoptosis using specific inhibitors of caspases. In the U-937 cells treated with DZA, cytochrome c release from mitochondria and subsequent activation of caspase-9, -8 and -3 were observed before the induction of apoptosis. zDEVD-Fmk, a specific inhibitor of caspase-3, and zLEHD-Fmk, a specific inhibitor of caspase-9, prevented the activation of caspase-8 but neither caspase-3 nor caspase-9, indicating that caspase-8 is downstream of both caspase-3 and caspase-9, which are activated by independent pathways. zVAD-Fmk, a universal inhibitor of caspases, kept the caspase-3 from being activated but not caspase-9. Moreover, ZB4, an antagonistic Fas-antibody, exerted no effect on the activation of caspase-8 and induction of apoptosis by DZA. In addition, zVAD-Fmk and mitochondrial permeability transition pore (MPTP) inhibitors such as cyclosporin A (CsA) and bongkrekic acid (BA) did not block the release of cytochrome c from mitochondria. Taken together, these results suggest that in the DZA-induced apoptosis, caspase-8 may serve as an executioner caspase and be activated downstream of both caspase-3 and caspase-9, independently of Fas receptor-ligand interaction. And caspase-3 seems to be activated by other caspses including IETDase-like enzyme and caspse-9 seems to be activated by cytochrome c released from mitochondria without the involvement of caspases and CsA- and BA- inhibitory MPTP.

Activation of caspase-8 in 3-deazaadenosine-induced apoptosis of U-937 cells occurs downstream of caspase-3 and caspase-9 without Fas receptor-ligand interaction

3-Deazaadenosine (DZA), a cellular methylation blocker was reported to induce the caspase-3-like activities-dependent apoptosis in U-937 cells. In this study, we analyzed the activation pathway of the caspase cascade involved in the DZA-induced apoptosis using specific inhibitors of caspases. In the U-937 cells treated with DZA, cytochrome c release from mitochondria and subsequent activation of caspase-9, -8 and -3 were observed before the induction of apoptosis. zDEVD-Fmk, a specific inhibitor of caspase-3, and zLEHD-Fmk, a specific inhibitor of caspase-9, prevented the activation of caspase-8 but neither caspase-3 nor caspase-9, indicating that caspase-8 is downstream of both caspase-3 and caspase-9, which are activated by independent pathways. zVAD-Fmk, a universal inhibitor of caspases, kept the caspase-3 from being activated but not caspase-9. Moreover, ZB4, an antagonistic Fas-antibody, exerted no effect on the activation of caspase-8 and induction of apoptosis by DZA. In addition, zVAD-Fmk and mitochondrial permeability transition pore (MPTP) inhibitors such as cyclosporin A (CsA) and bongkrekic acid (BA) did not block the release of cytochrome c from mitochondria. Taken together, these results suggest that in the DZA-induced apoptosis, caspase-8 may serve as an executioner caspase and be activated downstream of both caspase-3 and caspase-9, independently of Fas receptor-ligand interaction. And caspase-3 seems to be activated by other caspses including IETDase-like enzyme and caspse-9 seems to be activated by cytochrome c released from mitochondria without the involvement of caspases and CsA- and BA- inhibitory MPTP.

The anti-apoptotic effects of Caspase inhibitor Ⅰ on cultured hepatocytes / 中国普通外科杂志

0 05) Under the same treatment concentration of rsFasL or granzyme B, percentage in TUNEL positive staining and Caspase 3 activity in the experimental group were much lower than those in the control group ( P

Effect of Caspase inhibitor on apoptosis after intracerebral hemorrhage in rats / 临床神经病学杂志

Objective To study the effect of zVADfmk(a Caspase inhibitor) on Caspase-3 activation and neuronal apoptosis after intracerebral hemorrhage (ICH) in rats.Methods ICH model was made by stereotactic infusing 50?l autologous blood into the caudate nucleus. zVADfmk was given via intraventricular injection. TUNEL staining and immunohistochemitry method were used to detect the expression of apoptosis and Caspase-3 in cerebral tissues at different time point.Results After ICH, Caspase-3 and TUNEL positive cells increased obviously in the perihematomal brain edema zone compared with the pseudo-operation group ( P

Protective Effect of Caspase Inhibitor on Neonatal Rat with Hypoxia-Ischemia Brain Damage / 实用儿科临床杂志

Objective To observe the protection of Caspase inhibitor(zVAD-fmk,benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone) on neonatal rat with hypoxic-ischemic brain damage(HIBD).Methods Thirty-six neonatal rats,7 days old,were randomly divided into hypoxic-ischemic(HI) control group(A),zVAD-fmk treated group(B) and sham group(C).Before HI insult,a pan-Caspase inhibitor,zVAD-fmk or normal buffer solution was injected into the cerebral ventricle.The water content of cerebral hemisphere was measured and the percentage of apoptofic cells in hippocampal neurons was measured by Flow cytometer(Annexin V/PI) at 24 hours after HI insult.The effect on body weights(percentage of increased weight,WIP) and macroscopical changes(percentage of cortox and hippocampal dead neurons) were assessed at 14 days.Results Compared with group A,the water content of ischemic hemisphere and apoptosis percentage of hippocampal neurons in group B reduced significantly.The difference of percentage of increased weight at 14 days in group B was not significantly.Microscopic examination showed that cortox and hippocampus neural death rate in group B was proved significantly reduced compared with that in group A.Conclusion Intracerebral administration of zVAD-fmk has protective effects on hypoxic-ischemic brain damage in neonatal rat.