A grape-supplemented diet prevented ultraviolet (UV) radiation-induced cataract by regulating Nrf2 and XIAP pathways.

The purpose of this study is to investigate if grape consumption, in the form of grape powder (GP), could protect against ultraviolet (UV)-induced cataract. Mice were fed with the regular diet, sugar placebo diet, or a grape diet (regular diet supplemented with 5%, 10%, and 15% GP) for 3 months. The mice were then exposed to UV radiation to induce cataract. The results showed that the GP diet dose-dependently inhibited UV-induced cataract and preserved glutathione pools. Interestingly, UV-induced Nrf2 activation was abolished in the groups on the GP diet, suggesting GP consumption may improve redox homeostasis in the lens, making Nrf2 activation unnecessary. For molecular target prediction, a total of 471 proteins regulated by GP were identified using Agilent Literature Search (ALS) software. Among these targets, the X-linked inhibitor of apoptosis (XIAP) was correlated with all of the main active ingredients of GP, including resveratrol, catechin, quercetin, and anthocyanins. Our data confirmed that GP prevented UV-induced suppression of XIAP, indicating that XIAP might be one of the critical molecular targets of GP. In conclusion, this study demonstrated that GP protected the lens from UV-induced cataract development in mice. The protective effects of GP may be attributed to its ability to improve redox homeostasis and activate the XIAP-mediated antiapoptotic pathway.

XIAP, commonly targeted by tumor suppressive miR-3607-5p and miR-3607-3p, promotes proliferation and inhibits apoptosis in hepatocellular carcinoma.

MicroRNAs (miRNAs) are frequently aberrantly expressed in hepatocellular carcinoma (HCC) and are involved in its development. However, their role and mechanism in HCC are still not fully elucidated. Differential expression analysis and survival analysis were performed to identify potential miRNAs in HCC and miR-3607 was identified as a candidate therapeutic target and prognostic biomarker. RT-qPCR confirmed the low expression of mature miR-3607-3p and miR-3607-5p in HCC. Functional experiments suggested that both miR-3607-3p and miR-3607-5p significantly inhibited HCC proliferation and induced apoptosis. Next, the detailed mechanism of miR-3607-3p and miR-3607-5p in HCC was explored by combination of bioinformatic analysis and experimental validation, and uncovered that XIAP, a common target gene of miR-3607-3p and miR-3607-5p, was involoved in their tumor suppressive effects. Finally, a XIAP-associated protein-protein interaction network, consisting of 10 positively correlated genes, was established. Collectively, we for the first time suggest that miR-3607-3p and miR-3607-5p inhibit HCC by acting one common target XIAP.

The Effect of XIAP and Its Application in Tumor / 中国生物化学与分子生物学报

It has been found that X-linked inhibitor of apoptosis (XIAP) is the most characteristic and strongest inhibition of apoptosis proteins. The characteristic structures of XIAP are BIR domain and RING domain, which are important structures for XIAP to play an anti- apoptotic role. A variety of endogenous inhibitory proteins (XAF1, SMAC and OMI) can also inhibit XIAP’s anti-apoptotic effect in different ways. XIAP can directly inhibit the initiation and persistence of apoptosis pathway of caspase. XIAP participates in the death receptor pathway and mitochondrial pathway of inhibiting apoptosis in a variety of ways, such as directly binds to caspases, and activates NF-кB way and other signal pathways, which is essential for regulating the survival and development of tumor cells. XIAP is highly expressed in many kinds of tumor tissues. The high expression of XIAP is closely related to the occurrence and development, drug resistance, treatment and prognosis of tumors. XIAP deletion can significantly reduce the tumorigenicity of tumor cells, and XIAP is the downstream factor of cell apoptosis formed by blocking multiple signal pathways. Therefore, XIAP has become a new target for clinical anticancer drug design. At present, three potential directions of XIAP application in clinical treatment of cancer are small molecule inhibitors, antisense oligonucleotide inhibitors and XIAP gene silencing. This paper will introduce the biological function of XIAP against apoptosis and its role in the occurrence and development, drug resistance, treatment and prognosis of tumor diseases.

Sustained elevation of serum interleukin-18 and its association with hemophagocytic lymphohistiocytosis in XIAP deficiency.

X-linked lymphoproliferative syndrome (XLP) is a rare primary immunodeficiency characterized by increased vulnerability to Epstein-Barr virus infection. XLP type 1 is caused by mutations in SH2D1A, whereas X-linked inhibitor of apoptosis (XIAP) encoded by XIAP/BIRC4 is mutated in XLP type 2. In XIAP deficiency, hemophagocytic lymphohistiocytosis (HLH) occurs more frequently and recurrence is common. However, the underlying mechanisms remain mostly unknown. We describe the characteristics of the cytokine profiles of serum samples from 10 XIAP-deficient patients. The concentration of interleukin (IL)-18 was strikingly elevated in the patients presented with HLH, and remained high after the recovery from HLH although levels of other pro-inflammatory cytokines approached the normal range. Longitudinal examination of two patients demonstrated marked exacerbation of IL-18 levels during every occasion of HLH. These findings may suggest the association between HLH susceptibility and high serum IL-18 levels in XIAP deficiency.