Hyunho Kim

MCP-1 and RANTES Polymorphisms in Korean Diabetic End-Stage Renal Disease

Macrophage infiltration has been observed in the renal biopsy specimens of diabetic nephropathy (DN), and hyperglycemic state stimulates the renal expression of RANTES (regulated upon activation, normal T-cell expressed and secreted) and MCP-1 (monocyte chemoattractant protein-1). Upregulation of RANTES and MCP-1 with infiltrating macrophages may play a crucial role in the development and progression of DN. Genetic polymorphisms of RANTES and its receptors were reported to be independent risk factors for DN. We genotyped single nucleotide polymorphism (SNPs) in the MCP-1 G-2518A, CCR2 G46295A, RANTES C-28G and G-403A in 177 diabetic end-stage renal disease (ESRD) patients and 184 patients without renal involvement (controls) in order to investigate the effects of these SNPs on DN in Korean patients with type 2 DM. There were no differences in the frequencies of SNPs and the distribution of haplotypes of RANTES promoter SNPs between two groups. In conclusion, there were no associations of MCP-1, CCR2 and RANTES promoter SNPs with diabetic ESRD in Korean population. Prospective studies with clearly-defined, homogenous cohorts are needed to confirm the effect of these genetic polymorphisms on DN.

Calpain-mediated proteolysis of polycystin-1 C-terminus induces JAK2 and ERK signal alterations.

Autosomal dominant polycystic kidney disease (ADPKD), a hereditary renal disease caused by mutations in PKD1 (85%) or PKD2 (15%), is characterized by the development of gradually enlarging multiple renal cysts and progressive renal failure. Polycystin-1 (PC1), PKD1 gene product, is an integral membrane glycoprotein which regulates a number of different biological processes including cell proliferation, apoptosis, cell polarity, and tubulogenesis. PC1 is a target of various proteolytic cleavages and proteosomal degradations, but its role in intracellular signaling pathways remains poorly understood. Herein, we demonstrated that PC1 is a novel substrate for μ- and m-calpains, which are calcium-dependent cysteine proteases. Overexpression of PC1 altered both Janus-activated kinase 2 (JAK2) and extracellular signal-regulated kinase (ERK) signals, which were independently regulated by calpain-mediated PC1 degradation. They suggest that the PC1 function on JAK2 and ERK signaling pathways might be regulated by calpains in response to the changes in intracellular calcium concentration.

Akap12 is essential for the morphogenesis of muscles involved in zebrafish locomotion.

Swimming behavior in fish is driven by coordinated contractions of muscle fibers. In zebrafish, slow muscle cell migration is crucial for the formation of the muscle network; slow myoblasts, which arise from medial adaxial cells, migrate radially to the lateral surface of the trunk and tail during embryogenesis. This study found that the zebrafish A-kinase anchoring protein (akap)12 isoforms akap12α and akap12β are required for muscle morphogenesis and locomotor activity. Embryos deficient in akap12 exhibited reduced spontaneous coiling, touch response, and free swimming. Akap12-depleted slow but not fast muscle cells were misaligned, suggesting that the behavioral abnormalities resulted from specific defects in slow muscle patterning; indeed, slow muscle cells and muscle pioneers in these embryos showed abnormal migration in a cell-autonomous manner. Taken together, these results suggest that akap12 plays a critical role in the development of zebrafish locomotion by regulating the normal morphogenesis of muscles.

Second order PMD compensation using correlation factor between degree of polarization and depolarization rate

We proposed a new algorithm to calculate the feedback signal-depolarization rate for the second order PMD compensation. For this, we suggested the correlation between DOP and depolarization rate, and verified its validity through the analysis. With the application of this algorithm, the outage probability at 10/sup -12/ BER decreased by more than three times at averaged DGD value of 30 psec. The simulation results shows that the new algorithm will be useful in enhancing the system performance under severe PMD environment.