Coinduction of inducible nitric oxide synthase and arginine recycling enzymes in cytokine-stimulated PC12 cells and high output production of nitric oxide

Zhang, Wen Yi; Gotoh, Tomomi; Oyadomari, Seiichi; Mori, Masataka

doi:10.1016/s0169-328x(00)00154-6

Cited by 44 publications

(28 citation statements)

References 56 publications

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“…Insulin and growth hormone have negative influence on ASS in liver tissue but no effect in other tissue [66][67][68]. Cytokines, IL-Ib, interferon and TGF-b also can influence ASS expression [69,70]. Recently, it has been showed that glutamine stimulates ASS expression in rat hepatocytes and Caco-2 cells through O-glycosylation of Sp1.…”

Section: Why Ass Is Not Expressed In Certain Tumor Types ?mentioning

confidence: 99%

Arginine Deprivation as a Targeted Therapy for Cancer

Feun

You

et al. 2008

CPD

195

188

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Certain cancers may be auxotrophic for a particular amino acid and amino acid deprivation is one method to treat these tumors. Arginine deprivation is a novel approach to target tumors which lack argininosuccinate synthetase (ASS) expression. ASS is a key enzyme which converts citrulline to arginine. Tumors which usually do not express ASS include melanoma, hepatocellular carcinoma, some mesotheliomas and some renal cell cancers. Arginine can be degraded by several enzymes including arginine deiminase (ADI). Although ADI is a microbial enzyme from mycoplasma, it has high affinity to arginine and catalyzes arginine to citrulline and ammonia. Citrulline can be recycled back to arginine in normal cells which express ASS, whereas ASS(−) tumor cells cannot. A pegylated form of ADI (ADI-PEG20) has been formulated and has shown in vitro and in vivo activity against melanoma and hepatocellular carcinoma. ADI-PEG20 induces apoptosis in melanoma cell lines. However, arginine deprivation can also induce ASS expression in certain melanoma cell lines which can lead to in-vitro drug resistance. Phase I and II clinical trials with ADI-PEG20 have been conducted in patients with melanoma and hepatocellular carcinoma and antitumor activity has been demonstrated in both cancers. This article reviews our laboratory and clinical experience as well as others with ADI-PEG20 as an antineoplastic agent. Future direction in utilizing this agent is also discussed.

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Section: Why Ass Is Not Expressed In Certain Tumor Types ?mentioning

confidence: 99%

Arginine Deprivation as a Targeted Therapy for Cancer

Feun

You

et al. 2008

CPD

195

188

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“…Although in many hospital radiology units the radiation exposure remains below these levels, there is a higher risk for hospital workers handling diagnostic X-ray machines and γ-cameras due to the chronic but cumulative exposure to low doses of IR. One consequence of the exposure to IR is the formation of free radicals, such as peroxynitrites and hydroxyl radicals (Zhang et al, 2000;Spitz et al, 2004), able to produce some important alterations in the living cells. At DNA level, IR exerts its genotoxic effect by the induction of singleand double-strand breaks, a-basic sites and oxidized bases.…”

Section: Introductionmentioning

confidence: 99%

Increased frequency of chromosomal aberrations and sister chromatid exchanges in peripheral lymphocytes of radiology technicians chronically exposed to low levels of ionizing radiations

Santovito

Cervella

Delpero

2014

Environmental Toxicology and Pharmacology

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Chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) frequencies were estimated in peripheral lymphocytes from 21 radiology technicians, and from 21 nonexposed control subjects. We exclusively considered individuals who neither smoke nor consume drugs or alcohol for a period of at least two years prior to the analysis. Significant differences were found between exposed and controls in terms of SCEs and CAs frequencies. Technicians showed a significant higher number of high-frequency individuals (HFIs) with respect to the control group. Nevertheless, the mean frequency of SCEs observed among technician HFIs did not significantly differ with respect to that observed among control HFIs. Vice versa, the nonHFIs belonging to technicians group showed a statistically higher difference in the SCEs/NSM value with respect to the non-HFIs belonging to control group. Since the differences in the SCEs frequencies between the two groups are due to non-HFIs, our results seem to indicate a general genotoxic effect of the IR, not affected by HFIs. Among technicians, the level of chromosome damage correlated neither with years of radiation exposure nor with the age of the subjects. Vice versa, in the control group, a positive correlation was found between the number of SCEs and age. In both samples the gender status did not influence the frequencies of CAs and SCEs. Our results suggest that chronic long-term exposure to low doses of ionizing radiation could increase the CAs and SCEs frequencies. This study reinforces the relevance of the biomonitoring of hospital workers chronically exposed to ionizing radiation.

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“…Arginase II is expressed in kidney, small intestine and lactating mammary gland, and at lower levels in other tissues Vockley et al, 1996). AS (and also AL in some cases) is coinduced with iNOS in activated macrophages (Nussler et al, 1994;Nagasaki et al, 1996), vascular endothelial cells (Hattori et al, 1994), pancreatic b-cells (Flodstro Èm et al, 1995), glioma C6 cells (Zhang et al, 1999), microglial MG5 cells (Kawahara et al, 2001) and neuronal PC12 cells (Zhang et al, 2000), and upregulates NO synthesis. On the other hand, arginase I and/or II are also induced in activated macrophages and downregulate NO production (Sonoki et al, 1997;Louis et al, 1998;Morris et al, 1998;Salimuddin et al, 1999).…”

Section: Introductionmentioning

confidence: 99%