RESUMO
Polycystin-2 (also known as PC2, TRPP2, PKD2) is a major contributor to the underlying etiology of autosomal dominant polycystic kidney disease (ADPKD), which is the most prevalent monogenic kidney disease in the world. As a transient receptor potential (TRP) channel protein, PC2 exhibits cation-permeable, Ca2+-dependent channel properties, and plays a crucial role in maintaining normal Ca2+ signaling in systemic physiology, particularly in ADPKD chronic kidney disease. Structurally, PC2 protein consists of six transmembrane structural domains (S1-S6), a polycystin-specific “tetragonal opening for polycystins” (TOP) domain located between the S1 and S2 transmembrane structures, and cytoplasmic N- and C-termini. Although the cytoplasmic N-terminus and C-terminus of PC2 may not be significant in the gating of PC2 channels, there is still much protein structural information that needs to be thoroughly investigated, including the regulation of channel function and the assembly of homotetrameric ion channels. This is further supported by the presence of human disease-associated mutation sites on the PC2 structure. Moreover, PC2 synthesized in the endoplasmic reticulum is enriched in specific subcellular localization via membrane transport and can assemble itself into homotetrameric ion channels, as well as form heterotrimeric receptor-ion channel complexes with other proteins. These complexes are involved in a wide range of physiological functions, including the regulation of mechanosensation, cell polarity, cell proliferation, and apoptosis. In particular, PC2 assembles with chaperone proteins to form polycystic protein complexes that affect Ca2+ transport in cell membranes, cilia, endoplasmic reticulum, and mitochondria, and are involved in activating cell fate-related signaling pathways, particularly cell differentiation, proliferation, survival, and apoptosis, and more recently, autophagy. This leads to a shift of cystic cells from a normal uptake, quiescent state to a pathologically secreted, proliferative state. In conclusion, the complex structural and functional roles of PC2 highlight its critical importance in the pathogenesis of ADPKD, making it a promising target for therapeutic intervention.
RESUMO
TRPM8 (transient receptor potential melastatin 8), also known as a cold and menthol receptor and a member of the TRP (transient receptor potential) channel superfamily, locates on the cell membrane or organelle membrane.. TRPM8 is a non-selective cation channel, which can be used as either a cold and heat sensor or cold and pain sensor to conduct signal transduction. It plays an important role in maintaining intracellular homeostasis and controlling ion in cells. It has been found that PTM (post-translational modification) of TRPM8 affects the occurrence and development of many diseases by regulating the function of TRPM8 channel. Therefore, it is necessary to explore the PTM process of TRPM8 to gain a deeper understanding for the function and regulatory mechanism of TRPM8. At present, several types of post-translational modifications of TRPM8 have been reported, including phosphorylation, ubiquitination and glycosylation, which can regulate protein interactions and change the activity of TRPM8 ion channels, leading to modulation of cell proliferation, migration and apoptosis. It is noteworthy that the expression of TRPM8 level is closely related to many kinds of cancers, such as prostate cancer, bladder cancer and breast cancer. This review focus on the structure of TRPM8 ion channels, systematically elaborate the translational modifications, activator and antagonist of TRPM8 protein, and the regulation of some proteins on TRPM8 channel activity. At the same time, we summarize the recent progress of TRPM8 in prostate cancer, bladder cancer and breast cancer, which would provide new directions and new ideas for the treatment of cancer.
RESUMO
Objective To investigate the methods and efficacy of microscopic surgical treatment in patients with anterior communicating artery aneurysm. Methods The clinical data of 35 patients with ruptured anterior communicating artery aneurysm, admitted to our hospital from January 2008 to January 2011 and performed microneurosurgical treatment via pterional approch, were retrospective analyzed; their surgical techniques and efficacy were concluded. Results All the aneurysms in 35 patients were successfully clipped. Follow-up was performed for 3-6 months: complete recovery was achieved in 19 patients, good recovery in 11, and mild disability in 3 (including 1 with psychiatric symptom); death appeared in 2 patients. Conclusion The microsurgery via pterional approach is an effective method in treating anterior communicating artery aneurysms,resulting from its full exposure of aneurysms and few complications; adequate dissection and exposure of the entire H shaped complex body of anterior communicating artery are the keys to a successful clipping of aneurysm neck; and the selection of aneurysm clip suitable for the aneurysm and the preservation of the perforating arteries should be specially emphasized.