Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Schwann cell (SC) transplantation following spinal cord injury (SCI) may have therapeutic potential. Functional recovery is limited however, due to poor SC interactions with host astrocytes and the induction of astrogliosis. Olfactory ensheathing cells (OECs) are closely related to SCs, but intermix more readily with astrocytes in culture and induce less astrogliosis. We previously demonstrated that OECs express higher levels of sulfatases, enzymes that remove 6-O-sulfate groups from heparan sulphate proteoglycans, than SCs and that RNAi knockdown of sulfatase prevented OEC-astrocyte mixing in vitro. As human OECs are difficult to culture in large numbers we have genetically engineered SCs using lentiviral vectors to express sulfatase 1 and 2 (SC-S1S2) and assessed their ability to interact with astrocytes. We demonstrate that SC-S1S2s have increased integrin-dependent motility in the presence of astrocytes via modulation of NRG and FGF receptor-linked PI3K/AKT intracellular signaling and do not form boundaries with astrocytes in culture. SC-astrocyte mixing is dependent on local NRG concentration and we propose that sulfatase enzymes influence the bioavailability of NRG ligand and thus influence SC behavior. We further demonstrate that injection of sulfatase expressing SCs into spinal cord white matter results in less glial reactivity than control SC injections comparable to that of OEC injections. Our data indicate that sulfatase-mediated modification of the extracellular matrix can influence glial interactions with astrocytes, and that SCs engineered to express sulfatase may be more OEC-like in character. This approach may be beneficial for cell transplant-mediated spinal cord repair. GLIA 2016 GLIA 2017;65:19-33.
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PMID:Sulfatase-mediated manipulation of the astrocyte-Schwann cell interface. 2753 74

Human sulfatase 1 (hSulf-1) has aryl sulfatase activity. It can reduce the sulfation of cell surface heparan sulfate proteoglycan (HSPG) and inhibit various growth factor receptor-mediated signaling pathways. In most cancers, hSulf-1 is inactivated, which endows cancer cells with increasesed cell proliferation and metastatic activities, inhibition of apoptosis, and decreased sensitivity to radio- and chemotherapy. In this study, we found that hSulf-1 overexpression in melanoma cells can inhibit cell proliferation and induce cell cycle arrest and apoptosis by decreasing the protein kinase B (AKT) phosphorylation and limiting CDK4 nuclear import. We further confirmed that hSulf-1 overexpression can inhibit AKT phosphorylation and CDK4 nuclear localization and retard the growth of melanoma xenograft tumors in nude mice. Overall, hSulf-1 function in melanoma cells provides an ideal molecular treatment target. An important anti-tumor mechanism of hSulf-1 operates by decreasing downstream AKT signaling pathway activity and inhibiting the nuclear import of CDK4.
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PMID:Human sulfatase 1 exerts anti-tumor activity by inhibiting the AKT/ CDK4 signaling pathway in melanoma. 2780 23

Extracellular sulfatases, sulfatase 1 (Sulf1) and sulfatase 2 (Sulf2), play a pivotal role in cell signaling and carcinogenesis. Chemokine CCL5 inhibits Ang II-induced hypertensive mediators via angiotensin II (Ang II) type 2 receptor (AT2 R) pathway in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR). In this study, we investigated the effect of Sulfs on anti-hypertensive effects of CCL5 in SHR VSMCs. CCL5 attenuated Ang II-induced inhibition of sulfatase activity in SHR VSMCs. Inhibition of Ang II-induced 12-lipoxygenase (12-LO) and endothelin-1 (ET-1) expression by CCL5 was reduced in Sulf1 small interfering RNA (siRNA)-transfected SHR VSMCs. In addition, attenuation of Ang II-induced dimethylarginine dimethylaminohydrolase-1 (DDAH-1) inhibition by CCL5 was reduced in Sulf1 siRNA-transfected SHR VSMCs. Downregulation of Sulf2 did not affect inhibitory effects of CCL5 on Ang II-induced 12-LO and ET-1 expression and Ang II-induced inhibition of DDAH-1 expression in SHR VSMCs. Downregulation of Sulf1 abrogated the expression of CCL5-induced AT2 R messenger RNA (mRNA) and synergistic effect of CCL5 on Ang II-induced AT2 R expression in SHR VSMCs. These findings suggest that Sulf1 is a potential up-regulatory factor in anti-hypertensive actions of CCL5 via AT2 R pathway on Ang II-induced hypertensive effects in SHR VSMCs.
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PMID:Sulfatase 1 mediates the attenuation of Ang II-induced hypertensive effects by CCL5 in vascular smooth muscle cells from spontaneously hypertensive rats. 2968 35