Evidence that intracellular cyclophilin A and cyclophilin A/CD147 receptor-mediated ERK1/2 signalling can protect neurons against in vitro oxidative and ischemic injury

Boulos, Sherif; Meloni, Bruno P.; Arthur, Peter G.; Majda, Bernadette T.; Bojarski, Christina; Knuckey, Neville W.

doi:10.1016/j.nbd.2006.08.012

Cited by 109 publications

(96 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Astrocytes have been reported not to express CypA (43)(44)(45). Consistent with this report, we did not detect CypA expression in human normal astrocytes.…”

Section: Discussionsupporting

confidence: 91%

Cyclosporin A and sanglifehrin A enhance chemotherapeutic effect of cisplatin in C6 glioma cells

Han

Yoon²,

Ding³

et al. 2010

Oncol Rep

View full text Add to dashboard Cite

Abstract. Glioma is the most common type of brain tumors in adults, and treatment of high-grade gliomas is still palliative. Studies to date have revealed only modest effect in attenuating growth of these tumors with single agent therapy, but combination treatment appears to be more effective. Cyclophilin A (CypA), a target of immunosuppressive drugs cyclosporin A (CsA) and sanglifehrin A (SFA), is an intracellular protein that has peptidyl-prolyl cis-trans isomerase (PPIase) enzymatic activity. Previously, we showed that overexpressed CypA induced chemoresistance in cancer cells. Here we provide evidence that combination of cisplatin with either CsA or SFA synergistically enhances apoptotic cell death in C6 glioma cells, compared with single agent treatment. Enhanced apoptotic cell death is a result of an increase in ROS generation and a decrease in intracellular glutathione levels. Consistently, CypA knockdown by siRNA also enhances cisplatin-induced apoptosis. Immunohistochemical analysis showed increased expression of CypA in human glioblastoma multiforme, but not in normal human astrocytes. CypA was also shown to be up-regulated in C6 glioma cells during hypoxia. In conclusion, CsA or SFA in combination with cisplatin synergistically enhances cisplatin-induced apoptosis in C6 glioma cells via inhibition of PPIase activity of CypA, indicating that development of new drugs that selectively inhibit the CypA PPIase activity without immune suppression may facilitate alleviation of chemoresistance in treatment of high-grade glioma. IntroductionGlioma is the most common type of brain tumors in adults, and accounts for 25% of all brain tumors (1,2). Despite significant advances in cancer therapy, treatment of high-grade gliomas is still palliative. To date, the median survival for patients with high-grade gliomas, including glioblastoma multiforme (GBM; World Health Organization grade IV), is less than 1 year (3,4). Therefore, improved systemic treatment strategies are urgently required.Cyclophilin A (CypA), the prototypical member of the cyclophilin family, is a highly conserved protein in mammalian cells (5). CypA possesses enzymatic peptidyl-prolyl cis-trans isomerase (PPIase) activity, which is essential for protein folding in vivo. Although little is known about the function of CypA in cancer cells, it was recently reported that CypA is overexpressed in many cancer cells (6-11). In addition, our studies, as well as others, previously showed that overexpressed CypA protects cancer cells against cellular stresses, including hypoxia and cisplatin treatment, at least in part as a result of its antioxidant function (12)(13)(14)(15). These reports show that CypA might be important for tumorigenesis in solid tumors. CypA is also an immunophilin and a cytosolic receptor for the immunosuppressive drugs cyclosporin A (CsA) (5) and sanglifehrin A (SFA) (16). CsA binds to CypA, and this complex inhibits calcineurin, a calcium-dependent phosphatase, that regulates the expression of various cytokine genes ONCOLOGY REPORTS 2...

show abstract

“…Astrocytes have been reported not to express CypA (43)(44)(45). Consistent with this report, we did not detect CypA expression in human normal astrocytes.…”

Section: Discussionsupporting

confidence: 91%

Cyclosporin A and sanglifehrin A enhance chemotherapeutic effect of cisplatin in C6 glioma cells

Han

Yoon²,

Ding³

et al. 2010

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…CD147 has been shown to serve as a receptor for CyPA (Yurchenko et al 2002). The addition of CyPA to neuronal cultures resulted in activation of ERK1/2 (Boulos et al 2007), similar to the downstream signaling events observed upon CD147/CyPA association (Yurchenko et al 2002). CyPA levels are higher in the brain than they are in any other organ, predominantly localizing to neurons.…”

Section: Ischemic Diseasementioning

confidence: 68%

“…CD147, in conjunction with CyPA, has been reported to protect neurons from oxidative stress and ischemia (Boulos et al 2007). CD147 has been shown to serve as a receptor for CyPA (Yurchenko et al 2002).…”

Section: Ischemic Diseasementioning

confidence: 99%

CD147 immunoglobulin superfamily receptor function and role in pathology

Iacono

Brown

Greene

et al. 2007

Experimental and Molecular Pathology

233

206

View full text Add to dashboard Cite

The immunoglobulin superfamily member CD147 plays an important role in fetal, neuronal, lymphocyte and extracellular matrix development. Here we review the current understanding of CD147 expression and protein interactions with regard to CD147 function and its role in pathologic conditions including heart disease, Alzheimer's disease, stroke and cancer. A model linking hypoxic conditions found within the tumor microenvironment to up-regulation of CD147 expression and tumor progression is introduced.

show abstract

“…Our study demonstrates that similar regulation mechanisms are present in malignant gliomas. Elevated p-ERK1/2 levels are known to counteract glucose deprivation-induced cell death (Boulos et al, 2007), which may explain the protective effects of PEA-15 observed in glioblastoma cells. Given the absence of cell cycle-modulating effects of PEA-15, we propose that the PEA-15-dependent and ERK-mediated resistance is rather caused by antiapoptotic (anti-cell death) effects than by ERK-dependent regulation of the cell cycle or proliferation.…”

Section: Apoptosis In Brain Tumorsmentioning

confidence: 99%

The PEA-15/PED protein protects glioblastoma cells from glucose deprivation-induced apoptosis via the ERK/MAP kinase pathway

et al. 2007

View full text Add to dashboard Cite

Evidence that intracellular cyclophilin A and cyclophilin A/CD147 receptor-mediated ERK1/2 signalling can protect neurons against in vitro oxidative and ischemic injury

Cited by 109 publications

References 88 publications

Cyclosporin A and sanglifehrin A enhance chemotherapeutic effect of cisplatin in C6 glioma cells

Cyclosporin A and sanglifehrin A enhance chemotherapeutic effect of cisplatin in C6 glioma cells

CD147 immunoglobulin superfamily receptor function and role in pathology

The PEA-15/PED protein protects glioblastoma cells from glucose deprivation-induced apoptosis via the ERK/MAP kinase pathway

Contact Info

Product

Resources

About