Ching-Chang Cho - Academia.edu (original) (raw)

Papers by Ching-Chang Cho

Journal of Back and Musculoskeletal Rehabilitation, Jul 8, 2015

Cell Communication and Signaling, Jun 14, 2023

Background We previously reported that miR-195 exerts neuroprotection by inhibiting Sema3A and ce... more Background We previously reported that miR-195 exerts neuroprotection by inhibiting Sema3A and cerebral miR-195 levels decreased with age, both of which urged us to explore the role of miR-195 and miR-195-regulated Sema3 family members in age-associated dementia. Methods miR-195a KO mice were used to assess the effect of miR-195 on aging and cognitive functions. Sema3D was predicted as a miR-195 target by TargetScan and then verified by luciferase reporter assay, while effects of Sema3D and miR-195 on neural senescence were assessed by beta-galactosidase and dendritic spine density. Cerebral Sema3D was over-expressed by lentivirus and suppressed by si-RNA, and effects of over-expression of Sema3D and knockdown of miR-195 on cognitive functions were assessed by Morris Water Maze, Y-maze, and open field test. The effect of Sema3D on lifespan was assessed in Drosophila. Sema3D inhibitor was developed using homology modeling and virtual screening. One-way and two-way repeated measures ANOVA were applied to assess longitudinal data on mouse cognitive tests. Results Cognitive impairment and reduced density of dendritic spine were observed in miR-195a knockout mice. Sema3D was identified to be a direct target of miR-195 and a possible contributor to age-associated neurodegeneration as Sema3D levels showed age-dependent increase in rodent brains. Injection of Sema3D-expressing lentivirus caused significant memory deficits while silencing hippocampal Sema3D improved cognition. Repeated injections of Sema3D-expressing lentivirus to elevate cerebral Sema3D for 10 weeks revealed a time-dependent decline of working memory. More importantly, analysis of the data on the Gene Expression Omnibus database showed that Sema3D levels were significantly higher in dementia patients than normal controls (p < 0.001). Over-expression of homolog Sema3D gene in the nervous system of Drosophila reduced locomotor activity and lifespan by 25%. Mechanistically, Sema3D might reduce stemness and number of neural stem cells and potentially disrupt neuronal autophagy. Rapamycin restored density of dendritic spines in the hippocampus from mice injected with Sema3D lentivirus. Our novel small molecule increased viability of Sema3D-treated neurons and might improve autophagy efficiency, which suggested Sema3D could be a potential drug target. Conclusion Our results highlight the importance of Sema3D in age-associated dementia. Sema3D could be a novel drug target for dementia treatment.

Biomolecular Nmr Assignments, Jun 29, 2013

S100A15 (koebnerisin) is overexpressed in psoriatic skin and displays distinct localizations in s... more S100A15 (koebnerisin) is overexpressed in psoriatic skin and displays distinct localizations in skin and breast with divergent functions in inflammation. Here we report the backbone and side-chain resonance assignments for the Ca(2+)-bound human S100A15.

Biochemical and biophysical research communications, Jan 19, 2016

The human S100 protein family contains small, dimeric and acidic proteins that contain two EF-han... more The human S100 protein family contains small, dimeric and acidic proteins that contain two EF-hand motifs and bind calcium. When S100A5 binds calcium, its conformation changes and promotes interaction with the target protein. The extracellular domain of RAGE (Receptor of Advanced Glycation End products) contain three domains: C1, C2 and V. The RAGE V domain is the target protein of S100A5 that promotes cell survival, growth and differentiation by activating several signaling pathways. Pentamidine is an apoptotic and antiparasitic drug that is used to treat or prevent pneumonia. Here, we found that pentamidine interacts with S100A5 using HSQC titration. We elucidated the interactions of S100A5 with RAGE V domain and pentamidine using fluorescence and NMR spectroscopy. We generated two binary models-the S100A5-RAGE V domain and S100A5-Pentamidine complex-and then observed that the pentamidine and RAGE V domain share a similar binding region in mS100A5. We also used the WST-1 assay to ...

Biomolecular NMR Assignments, 2008

1 H, 15 N, and 13 C NMR assignments for 116 amino acids (Gly893-Lys1008) of a bacterial collagenb... more 1 H, 15 N, and 13 C NMR assignments for 116 amino acids (Gly893-Lys1008) of a bacterial collagenbinding domain (CBD) derived from Clostridium histolyticum class I collagenase were accomplished. Clostridial collagenases hydrolyze insoluble collagen. One to three copies of collagenbinding domains (CBDs) are present at their C-termini, each of which is the minimal segment required for the binding to the insoluble substrate. CBD has been shown to be able to anchor fused growth factors for up to 10 days in vivo. Structural analysis of the small domain with the unique function provides insights into designing a novel drug delivery vehicle by the rational drug design.

$Research paper thumbnail of Crystallization and Preliminary X-ray Diffraction Analysis of PAT, an Acetyltransferase from Sulfolobus solfataricus$

Sulfolobus solfataricus that specifically acetylates the chromatin protein Alba. The enzyme was e... more Sulfolobus solfataricus that specifically acetylates the chromatin protein Alba. The enzyme was expressed, purified and subsequently crystallized using the sitting-drop vapour-diffusion technique. Native diffraction data were collected to 1.70 Å resolution on the BL13C1 beamline of NSRRC from a flash-frozen crystal at 100 K. The crystals belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 44.30, b = 46.59, c = 68.39 Å .

Renal failure, 2017

The renin-angiotensin system (RAS) has significant influences on heart and renal disease progress... more The renin-angiotensin system (RAS) has significant influences on heart and renal disease progression. Angiotensin converting enzyme (ACE) and angiotensin converting enzyme II (ACE2) are major peptidases of RAS components and play counteracting functions through angiotensin II (Ang II)/ATIR and angiotensin-(1-7) (Ang-(1-7))/Mas axis, respectively. There were 360 uremic patients on regular hemodialysis (HD) treatment (inclusive of 119 HD patients with cardiovascular diseases (CVD) and 241 HD patients without CVD and 50 healthy subjects were enrolled in this study. Plasma ACE, ACE2, Ang II and Ang-(1-7) levels of the HD patients were determined. We compared pre-HD levels of plasma ACE, ACE2, Ang II and Ang-(1-7) in the HD patients with and without CVD to those of the controls. The HD patients, particularly those with CVD, showed a significant increase in the levels of ACE and Ang II, whereas ACE2 and Ang-(1-7) levels were lower than those in the healthy controls. Therefore, imbalanced ...

Journal of biomolecular NMR, Jan 9, 2015

The S100 proteins constitute the largest family within the EF-hand protein superfamily, shown to ... more The S100 proteins constitute the largest family within the EF-hand protein superfamily, shown to bind and control various proteins involved in several cellular functions such as proliferation, differentiation, apoptosis, Ca 2? homeostasis, and energy metabolism (Donato et al. 2013; Hermann et al. 2012; Leclerc and Heizmann 2011). They regulate a wide range of important cellular processes via protein-protein interactions (Schafer and Heizmann 1996). Calcium interactions with the EF-hand motifs result in a conformation change of target protein binding by exposing hydrophobic regions in S100 proteins (Smith and Shaw 1998). The calcium binding EF-hand motif starts the action with structural changes in the S100 proteins, allowing them to interact through target selectivity (Yap et al. 1999; Zimmer and Weber 2010). The protein S100A4 was first derived from both tumor and stroma. It is a homodimeric protein in solution and has been shown to function as a metastasis-promoting protein (Ambartsumian et al. 2005; Ismail et al. 2010). Its presence has now been well documented in many cancers including breast, colorectal, gastric, pancreatic, and bladder cancers. It plays a role in tumor formation and angiogenesis (Ambartsumian et al. 2001; Barraclough et al. 2009; Ford and Zain 1995). The hinge region and C-terminal EF-hand of the S100A4 protein are unique compared to other S100 proteins; however most S100 proteins are involved in target protein binding. The binding of calcium ions produces conformational changes in proteins resulting in exposure of the hydrophobic pocket of residues in helices 3 and 5, the hinge region, and the C-terminal EF-hand (Malashkevich et al. 2008; Mishra et al. 2012; Semov et al. 2005). Previous results have provided insights into the dynamic mechanism of the C-terminal in S100A4 as a mediator of S100A4-driven metastasis, and they highlight its role in tuning the Ca 2?-binding affinity of S100A4. These results also suggest that locking the C-terminus to the core domain may be an alternative strategy for inhibiting its metastasispromoting activities (Duelli et al. 2014). In this study, we mutated four cysteine residues (Cys3, Cys76, Cys81, and Cys86) on S100A4 to serine. The Cys3 residue is located very near the N-terminus, and the remaining three are in helix 4 (H4) (Pathuri et al. 2008). We labeled this protein 'mutant S100A4' and determined the three-dimensional structure of the calcium-bound of this protein using NMR. With this structure solved, we could explain why full length S100A4 has weaker calcium-binding affinity than its truncated form, where the last 13 amino acids in the C-terminal are deleted. Methods and results Protein expression and purification Wild type human S100A4 contains four cysteine residues. One is at the N-terminal position of the amino acid sequence, and the remaining three are in the H4 region in the presence of DTT as a reducing agent, necessary in NMR buffer conditions. To study the three-dimensional structure Electronic supplementary material The online version of this article (

International Journal of Environmental Research and Public Health, 2018

Air pollution is a very critical issue worldwide, particularly in developing countries. Particula... more Air pollution is a very critical issue worldwide, particularly in developing countries. Particulate matter (PM) is a type of air pollution that comprises a heterogeneous mixture of different particle sizes and chemical compositions. There are various sources of fine PM (PM 2.5), and the components may also have different effects on people. The pathogenesis of PM 2.5 in several diseases remains to be clarified. There is a long history of epidemiological research on PM 2.5 in several diseases. Numerous studies show that PM 2.5 can induce a variety of chronic diseases, such as respiratory system damage, cardiovascular dysfunction, and diabetes mellitus. However, the epidemiological evidence associated with potential mechanisms in the progression of diseases need to be proved precisely through in vitro and in vivo investigations. Suggested mechanisms of PM 2.5 that lead to adverse effects and chronic diseases include increasing oxidative stress, inflammatory responses, and genotoxicity. The aim of this review is to provide a brief overview of in vitro and in vivo experimental studies of PM 2.5 in the progression of various diseases from the last decade. The summarized research results could provide clear information about the mechanisms and progression of PM 2.5-induced disease.

PloS one, 2016

The human S100A4 protein binds calcium, resulting in a change in its conformation to promote the ... more The human S100A4 protein binds calcium, resulting in a change in its conformation to promote the interaction with its target protein. Human epidermal growth factor (EGF) is the target protein of S100A4 and a critical ligand of the receptor EGFR. The EGF/EGFR system promotes cell survival, differentiation, and growth by activating several signaling pathways. Amlexanox is an anti-inflammatory and anti-allergic drug that is used to treat recurrent aphthous ulcers. In the present study, we determined that amlexanox interacts with S100A4 using heteronuclear single quantum correlation titration. We elucidated the interactions of S100A4 with EGF and amlexanox using fluorescence and nuclear magnetic resonance spectroscopy. We generated two binary models (for the S100A4-EGF and S100A4-amlexanox complexes) and observed that amlexanox and EGF share a similar binding region in mS100A4. We also used a WST-1 assay to investigate the bioactivity of S100A4, EGF, and amlexanox, and found that amlexa...

Biochemistry, 2014

The membrane form of heparin binding EGF-like growth factor (proHB-EGF) yields secreted HB-EGF an... more The membrane form of heparin binding EGF-like growth factor (proHB-EGF) yields secreted HB-EGF and a membrane-anchored cytoplasmic tail (proHB-EGF-CT), which may be targeted to the nuclear membrane after a shedding stimulus. Bcl-2-associated athanogene 1 (BAG-1) accumulates in the nuclei and inhibits apoptosis in adenoma-derived cell lines. The maintenance of high levels of nuclear BAG-1 enhances cell survival. However, the ubiquitin homology domain of BAG-1 from Mus musculus (mBAG-1-UBH) is proposed to interact with proHB-EGF-CT, and this interaction may enhance the cytoprotection against the apoptosis inducer. The mechanism of the synergistic anti-apoptosis function of proHB-EGF-CT and mBAG-1-UBH is still unknown. We offer a hypothesis that proHB-EGF-CT can maintain high levels of nuclear BAG-1. In this study, we first report the three-dimensional nuclear magnetic resonance structure of proHB-EGF-CT complexed with mBAG-1-UBH. In the structure of the complex, the residues in the C-terminus and one turn between β-strands β1 and β2 of mBAG-1-UBH bind to two terminals of proHB-EGF-CT, which folds into a loop with end-toend contact. This end-to-end folding of proHB-EGF-CT causes the basic amino acids to colocalize and form a positively charged groove. The dominant forces in the binding interface between proHB-EGF-CT and mBAG-1-UBH are charge−charge interactions. On the basis of our mutagenesis results, the basic amino acid cluster in the N-terminus of proHB-EGF-CT is the crucial binding site for mBAG-1-UBH, whereas another basic amino acid in the C-terminus facilitates this interaction. Interestingly, the mBAG-1-UBH binding region on the proHB-EGF-CT peptide is also involved in the region found to be important for nuclear envelope targeting, supporting the hypothesis that proHB-EGF-CT is most likely able to trigger the nuclear translocation of BAG-1 in keeping its level high.