Inhibition of the α-mannosidase Man2c1 gene expression enhances adhesion of Jurkat cells

Li, Qu; Ju, Ji Yu; Chen, Shuang Ling; Shi, Yan; Xiang, Zhi; Zhou, Yanxiang; Tian, Yun; Liu, Yin; Zhu, Li

doi:10.1038/sj.cr.7310065

Cited by 10 publications

(11 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most studies of the biological significance of a-mannosidases have been performed at the cell level (Goss et al 1995;Asano 2003;Shi et al 2001Shi et al , 2002Qu et al 2006;Yue et al 2004;Tian et al 2008;Suzuki et al 2006). In further evaluations the significance of a few gene knockout mouse models have been studied.…”

Section: Discussionmentioning

confidence: 98%

“…In this laboratory Man2c1 suppression was found to cause oncosis-like death of BJAB human B lymphoma cell (Shi et al 2002), resistance of SKW6 Epstein-Barr virus-transformed human B cell to apoptosis induction by antiFas antibody (Shi et al 2001), enhancement of adhesiveness of Jurkat human T lymphoma cell (Qu et al 2006), and reduction of malignant activities of CNE-2L2 human nasopharyngeal carcinoma cell (Yue et al 2004) and EC9706 human esophageal carcinoma cell . Growth inhibition of Hek293 human embryonal kidney cell by Man2c1 suppression was also observed by Suzuki et al (2006).…”

Section: Introductionmentioning

confidence: 98%

“…In a study of the biological significance of a-mannosidase, researchers used chemicals to inhibit a-mannosidase activity (Goss et al 1995;Asano 2003), or the antisense technique (Shi et al 2001(Shi et al , 2002Qu et al 2006;Yue et al 2004)/short interfering RNA technique Suzuki et al 2006) to inhibit specific a-mannosidase expression in cells, or the gene knockout technique to inactivate an a-mannosidase gene in mice (Chui et al 1997;Fukuda and Akama 2002). In this laboratory Man2c1 suppression was found to cause oncosis-like death of BJAB human B lymphoma cell (Shi et al 2002), resistance of SKW6 Epstein-Barr virus-transformed human B cell to apoptosis induction by antiFas antibody (Shi et al 2001), enhancement of adhesiveness of Jurkat human T lymphoma cell (Qu et al 2006), and reduction of malignant activities of CNE-2L2 human nasopharyngeal carcinoma cell (Yue et al 2004) and EC9706 human esophageal carcinoma cell .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

hMan2c1 transgene promotes tumor progress in mice

et al. 2009

View full text Add to dashboard Cite

In order to study the biological significance of alpha-mannosidase Man2c1, hMan2c1 transgenic mice were developed. In 113 F0 mice, eight were found to be genomic PCR positive for hMan2c1; 9/20 (45%) F1 mice, 16/21 (76.2%) F2 mice, and 12/14 (85.7%) F3 mice were genomic PCR positive for hMan2c1. RT-PCR demonstrated hMan2c1 mRNA transcription in four of eight transgenic lines. Enzymatic activity on p-nitrophenyl-alpha-D: -mannopyranoside was enhanced in 35# and 54# transgenic mice and real-time RT-PCR showed hMan2c1 mRNA expression in these mice. Reduced Con A binding to splenocytes implied N-glycosylation modification of host proteins by hMan2c1 transgene. hMan2c1 transgene promoted growth, invasion, and metastasis to lung of implanted hepatoma H22 and sarcoma S180. The average weights of H22 and S180 tumors were 3.98 +/- 1.62, 3.29 +/- 0.76, 1.69 +/- 1.09, and 3.19 +/- 0.44, 2.72 +/- 1.38, 0.97 +/- 0.41 g for 35#, 54# transgenic mice and wild type mice (W), respectively, (35# or 54# versus W, paired t-test, P < 0.05). In 35# and 54# mice 5/10 and 3/10 showed lung metastasis of H22 tumor in contrast with 1/10 in W mice. In 35# and 54# mice 1/6 and 2/6 showed lung metastasis of S180 tumor in contrast with 0/6 in W mice. The possible mechanism of the promotion was explored on both humoral and cellular immunity. Reduced antibody response to BSA was observed in transgenic mice, suggesting that specific antibody response to tumor antigens might be suppressed by hMan2c1 transgene. However, NK cytotoxicity in splenocytes was not affected by the transgene.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

hMan2c1 transgene promotes tumor progress in mice

et al. 2009

View full text Add to dashboard Cite

show abstract

“…The ability of Treg KIF to bind to ICAM-1 was reduced suggesting that correct N-glycosylation of LFA-1 may facilitate Treg binding to ICAM-1. Interestingly, blocking MAN2C1, which is another enzyme in the N-glycosylation pathway downstream of alpha-1,2-mannosidase, results in increased binding of Jurkat human T cells to ICAM-1 [37]. Therefore the ability of Treg proteins to bind to ligands may depend on their terminal oligosaccharides.…”

Section: Discussionmentioning

confidence: 99%

Alpha-1,2-Mannosidase and Hence N-Glycosylation Are Required for Regulatory T Cell Migration and Allograft Tolerance in Mice

et al. 2010

View full text Add to dashboard Cite

BackgroundSpecific immunological unresponsiveness to alloantigens can be induced in vivo by treating mice with a donor alloantigen in combination with a non-depleting anti-CD4 antibody. This tolerance induction protocol enriches for alloantigen reactive regulatory T cells (Treg). We previously demonstrated that alpha-1,2-mannosidase, an enzyme involved in the synthesis and processing of N-linked glycoproteins, is highly expressed in tolerant mice, in both graft infiltrating leukocytes and peripheral blood lymphocytes.Principal FindingsIn this study we have identified that alpha-1,2-mannosidase expression increases in CD25+CD4+ Treg when they encounter alloantigen in vivo. When alpha-1,2-mannosidase enzyme activity was blocked, Treg retained their capacity to suppress T cell proliferation in vitro but were unable to bind to physiologically relevant ligands in vitro. Further in vivo analysis demonstrated that blocking alpha-1,2-mannosidase in Treg resulted in the migration of significantly lower numbers to the peripheral lymph nodes in skin grafted mice following adoptive transfer, where they were less able to inhibit the proliferation of naïve T cells responding to donor alloantigen and hence unable prevent allograft rejection in vivo.SignificanceTaken together, our results suggest that activation of alloantigen reactive Treg results in increased alpha-1,2-mannosidase expression and altered N-glycosylation of cell surface proteins. In our experimental system, altered N-glycosylation is not essential for intrinsic Treg suppressive capacity, but is essential in vivo as it facilitates Treg migration to sites where they can regulate immune priming. Migration of Treg is central to their role in regulating in vivo immune responses and may require specific changes in N-glycosylation upon antigen encounter.

show abstract

“…Nevertheless, the locus is known to be involved in cancer progression, as its expression appears to modulate tumor growth in in vivo [29,30] experiments. In addition, both in vitro [31,32] and in vivo [32] work has implicated MAN2C1 in T-cell functioning, and yeast two hybrid assays have shown that it interacts with an immune-system related gene, HLA-B associated transcript 2 (BAT2) [33]. Both gene expression [17][18][19] and methylation [16] studies of PTSD have indicated that dysregulation in immune system related genes in peripheral blood are associated with this disorder.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression and Methylation Signatures ofMAN2C1are Associated with PTSD

et al. 2011

View full text Add to dashboard Cite

Abstract. As potential regulators of DNA accessibility and activity, epigenetic modifications offer a mechanism by which the environment can moderate the effects of genes. To date, however, there have been relatively few studies assessing epigenetic modifications associated with post-traumatic stress disorder (PTSD). Here we investigate PTSD-associated methylation differences in 33 genes previously shown to differ in whole blood-derived gene expression levels between those with vs. without the disorder. Drawing on DNA samples similarly obtained from whole blood in 100 individuals, 23 with and 77 without lifetime PTSD, we used methylation microarray data to assess whether these 33 candidate genes showed epigenetic signatures indicative of increased risk for, or resilience to, PTSD. Logistic regression analyses were performed to assess the main and interacting effects of candidate genes' methylation values and number of potentially traumatic events (PTEs), adjusting for age and other covariates. Results revealed that only one candidate gene -MAN2C1 -showed a significant methylation x PTE interaction, such that those with both higher MAN2C1 methylation and greater exposure to PTEs showed a marked increase in risk of lifetime PTSD (OR 4.35, 95% CI: 1.07, 17.77, p = 0.04). These results indicate that MAN2C1 methylation levels modify cumulative traumatic burden on risk of PTSD, and suggest that both gene expression and epigenetic changes at specific loci are associated with this disorder.

show abstract

Inhibition of the α-mannosidase Man2c1 gene expression enhances adhesion of Jurkat cells

Abstract: Protein N-glycosylation plays very important roles in immunity and a-mannosidase is one of the key enzymes in Nglycosylation. This paper reports that inhibition of a-mannosidase Man2c1 gene expression enhances adhesion of Jurkat

Cited by 10 publications

References 29 publications

hMan2c1 transgene promotes tumor progress in mice

hMan2c1 transgene promotes tumor progress in mice

Alpha-1,2-Mannosidase and Hence N-Glycosylation Are Required for Regulatory T Cell Migration and Allograft Tolerance in Mice

Gene Expression and Methylation Signatures ofMAN2C1are Associated with PTSD

Contact Info

Product

Resources

About