• BMB Reports
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• 제48권3호
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• pp.184-189
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• 2015

Src homology 2-containing protein tyrosine phosphatase 2 (SHP-2) is known to protect neurons from neurodegeneration during ischemia/reperfusion injury. We recently reported that ROS-mediated oxidative stress promotes phosphorylation of endogenous SHP-2 in astrocytes and complex formation between caveolin-1 and SHP-2 in response to oxidative stress. To examine the region of SHP-2 participating in complex formation with caveolin-1, we generated three deletion mutant constructs and six point mutation constructs of SHP-2. Compared with wild-type SHP-2, binding of the N-SH2 domain deletion mutant of SHP-2 to p-caveolin-1 was reduced greatly, using flow cytometric competitive binding assays and surface plasmon resonance (SPR). Moreover, deletion of the N-SH2 domain of SHP-2 affected $H_2O_2$-mediated ERK phosphorylation and Src phosphorylation at Tyr 419 in primary astrocytes, suggesting that N-SH2 domain of SHP-2 is responsible for the binding of caveolin-1 and contributes to the regulation of Src phosphorylation and activation following ROS-induced oxidative stress in brain astrocytes.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2219-2225
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• 2015

SHP1 negatively regulates the Janus kinase 2/signal transducer and activator of transcription (JAK2/STAT) signaling pathway, which is constitutively activated in myeloproliferative neoplasms (MPNs) and leukemia. Promoter hypermethylation resulting in epigenetic inactivation of SHP1 has been reported in myelomas, leukemias and other cancers. However, whether SHP1 hypermethylation occurs in MPNs, especially in Chinese patients, has remained unclear. Here, we report that aberrant hypermethylation of SHP1 was observed in several leukemic cell lines and bone marrow mononuclear cells from MPN patients. About 51 of 118 (43.2%) MPN patients including 23 of 50 (46%) polycythaemia vera patients, 20 of 50 (40%) essential thrombocythaemia and 8 of 18 (44.4%) idiopathic myelofibrosis showed hypermethylation by methylation-specific polymerase chain reaction. However, SHP1 methylation was not measured in 20 healthy volunteers. Hypermethylation of SHP1 was found in MPN patients with both positive (34/81, 42%) and negative (17/37, 45.9%) JAK2V617F mutation. The levels of SHP1 mRNA were significantly lower in hypermethylated samples than unmethylated samples, suggesting SHP1 may be epigenetically inactivated in MPN patients. Furthermore, treatment with 5-aza-2'-deoxycytidine (AZA) in K562 cells showing hypermethylation of SHP1 led to progressive demethylation of SHP1, with consequently increased reexpression of SHP1. Meanwhile, phosphorylated JAK2 and STAT3 were progressively reduced. Finally, AZA increased the expression of SHP1 in primary MPN cells with hypermethylation of SHP1. Therefore, our data suggest that epigenetic inactivation of SHP1 contributes to the constitutive activation of JAK2/STAT signaling. Restoration of SHP1 expression by AZA may contribute to clinical treatment for MPN patients.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.4117-4123
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• 2016

Background: Methylation of promoter 2 of the SHP1 gene is epithelial cell specific, with reported potential as a lymph node metastatic marker. Objective: To demonstrate SHP1-P2 methylation-specific quantitative PCR effectiveness in detecting colorectal cancer (CRC) DNA in lymph nodes. Materials and Methods: SHP1-P2 methylation levels were measured in lymph nodes of CRC patients and compared with pathological findings and patient prognosis. Results: Lymph nodes of CRC metastatic patients without microscopically detectable cancer cells had higher SHP1-P2 methylation levels than lymph nodes of controls (p<0.001). In addition, a higher SHP1-P2 methylation level was associated with a shorter duration until adverse disease events, metastasis, recurrence and death (r2 = 0.236 and p value = 0.048). Studying two cohorts of 74 CRC patients without microscopic lymph node metastases showed that only the cohort containing samples with high SHP1-P2 methylation levels had a significant hazard ratio of 3.8 (95%CI = 1.02 to 14.2). Conclusions: SHP1-P2 methylation PCR can detect CRC DNA in lymph nodes even if cancer cells are not visible under a microscope, confirming applicability as a potential universal lymph node metastatic marker.

• Molecules and Cells
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• 제23권3호
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• pp.331-339
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• 2007

It has been suggested that the structure and function of nuclear receptors are evolutionally conserved. Here, we compare the molecular functions of the nile tilapia (Oreochromis niloticus) small heterodimer partner (nSHP/NR0B2) and the Dosage-sensitive sex reversal AHC critical region on X chromosome gene 1 (nDAX-1/NR0B1) with those of human SHP and DAX-1 (hSHP and hDAX-1, respectively). We found that, upon transient cotransfection of human cells, nDAX-1 repressed the activity of tilapia SF-1 (nSF-1) but not that of human SF-1, although the physical interaction with human SF-1 was retained. Similarly, nSHP repressed the activity of nSF-1, whereas hSHP did not, pointing to divergent evolution of SHP/SF-1 in fish and human. We thus propose that the repressive functions of SHP and DAX-1 have been conserved in fish and mammals although with different transcriptional targets and mechanisms. These differences provide new insights into the physiological diversification of atypical orphan nuclear receptors during vertebrate evolution.

• 한국식품영양과학회지
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• 제37권9호
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• pp.1196-1201
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• 2008

함초 분말을 이용한 식빵의 품질에 대해 검토하였다. 함초분말 첨가에 의해 식빵의 조섬유, 칼슘 그리고 철분함량이 뚜렷하게 증가하였으며, pH는 함초 첨가 식빵이 대조구에 비해 높았다. 함초 분말을 0.6%에서 2.4%까지 첨가한 식빵의 염도는 대조구와 유의적인 차이를 나타내지 않았다. 함초분말 첨가 식빵의 표면 색도는 대조구에 비해 L값과 b값은 감소하였으나 a값은 증가하였고, 빵 내부의 색도는 함초 분말 첨가량 1.8%까지는 대조구와 유의적인 차이를 나타내지 않았다. 함초를 첨가한 식빵의 조직감(hardness, spinginess, chewiness, cohesiveness)은 대조구보다 높았으며, 함초 첨가량이 증가할수록 증가하였다. 식빵의 전자공여능을 조사한 결과, 함초 분말 0.6, 1.2 1.8, 2.4 및 6.0% 첨가구 각각 30.42, 33.91, 39.51, 41.17 및 63.82%로 대조구의 27.95%보다 높았으며, 함초 첨가량이 증가할수록 식빵의 지방산패 억제 활성은 증가하였고 폴리페놀 함량도 증가하였다.

• 한국학교보건학회지
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• 제31권3호
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• pp.157-166
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• 2018

Purpose: This review aimed to provide a new perspective on School Heath Promotion (SHP) in the context of Korea's school system. Methods: Relevant literature and reports on SHP were investigated. On the basis of the analysis, this review closely examined how SHP had been developed, and what has been happening in the recent years of SHP in advanced nations. Results: Major findings from this review in terms of finding a new perspective on SHP in Korea were to: 1) share awareness of the fundamentals of SHP; 2) establish a national framework for school-based SHP; 3) build a cooperative SHP governance; 4) strengthen a SHP monitoring and evaluation system; 5) integrate health and education. Conclusion: Recently, serious student health threats have been putting pressure on schools in Korea. This review will serve as a critical implication of how to effectively implement SHP in Korea.

• Journal of Digestive Cancer Research
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• 제6권1호
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• pp.6-10
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• 2018

The importance of signal transducer and activator of transcription 3 (STAT3) signaling in gastric carcinogenesis was firmly evaluated in the previous studies. Fully activated STAT3 induces various target genes involving tumor invasion and epithelial-mesenchymal transition (EMT), and mediates interaction between cancer cells and microenvironmental immune cells. Thus, suppression of STAT3 activity is an important issue for inhibition of gastric carcinogenesis and invasion. Unfortunately, data from clinical studies of direct inhibitor targeting STAT3 have been disappointing. SH2-containing protein tyrosine phosphatase 1 (SHP-1) effectively dephosphorylates and inhibits STAT3 activity, which has not been extensively studied gastric cancer research field. However, by summarizing recent data, it is evident that protein and gene expression of SHP-1 are minimal in gastric cancer cells, and induction of SHP-1 effectively downregulates phosphorylated STAT3 and inhibits cellular invasion in gastric cancer cells. Several SHP-1 inducers have been investigated in the experimental studies, including proton pump inhibitor, arsenic trioxide, and other natural compounds. Taken together, we suggest that modulation of SHP-1/STAT3 signaling axis may present a new way for treatment of gastric cancer, and development of effective SHP-1 inducer may be an important task in the future search field of gastric cancer.

• Journal of Acupuncture Research
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• 제22권1호
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• pp.1-11
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• 2005

한약복합처방(SHP)의 약침 및 경구투여가 STZ으로 유발된 흰쥐의 당뇨병과 항산화능에 미치는 영향을 연구한 결과 다음과 같은 결론을 얻었다. 1. In vitro 에서 SHP은 ${\alpha}$-glucosidase 저해 및 DPPH 라디칼 소거 활성을 나타냈으며, t-BHP에 의한 신장 피질 조직에서의 지질 과산화 생성을 억제하였다. 2. SHP은 대조군에 비해 STZ에 의한 혈청 중 insulin 함량 저하를 유의성있게 증가시켰으며, 혈청 중 glucose 함량변화에 있어서도 유의성 있게 감소시켰다. 3. SHP은 대조군에 비해 STZ에 의해 상승된 혈청 중 triglyceride 함량을 유의성있게 감소시켰고, 혈청 중 total cholesterol 함량을 감소시키는 경향을 보였으나 유의성은 없었다. 4. STZ 투여로 인해 혈청 내 지질과산화물의 함량이 증가되었으며 SHP의 약침 및 경구투여로 감소되는 경향을 보였으나 유의성은 없었다. 5. STZ에 의해 증가된 catalase 활성은 SHP에 의해 감소되는 경향을 보였으나 유의성은 없었으며, glutathione 활성 역시 SHP에 의해 감소되는 경향을 보였으나 유의성은 없었다.

• 한국가축번식학회지
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• 제15권3호
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• pp.201-205
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• 1991

This study was carried out to investigate the effects of Ca and BSA on hydrogen ion concentration in sperm washed solution. The results obtained were as follows : 1. The hydrogen concentration in 1st and 2nd sperm washed solutions was signifcinatly(p<0.01) higher when sperm was washed with SHPsolution containing 2mM Ca than when sperm washed with SHP solution or SHP solution containing 10mM Ca. 2. The hydrogen ion concentration in sperm washed solution was significnatly(p<0.05) higher when seprm was washed with SHP solution containing BSA-FAF than when sperm was washed with SHP solution or SHP solution containing BSA-V.

• BMB Reports
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• 제49권3호
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• pp.173-178
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• 2016

Liver cells experience hypoxic stress when drug-metabolizing enzymes excessively consume O₂ for hydroxylation. Hypoxic stress changes the transcription of several genes by activating a heterodimeric transcription factor called hypoxia-inducible factor-1α/β (HIF-1α/β). We found that hypoxic stress (0.1% O₂) decreased the expression of cytochrome P450 7A1 (CYP7A1), a rate-limiting enzyme involved in bile acid biosynthesis. Chenodeoxycholic acid (CDCA), a major component of bile acids, represses CYP7A1 by activating a transcriptional repressor named small heterodimer partner (SHP). We observed that hypoxia decreased the levels of both CDCA and SHP, suggesting that hypoxia repressed CYP7A1 without inducing SHP. The finding that overexpression of HIF-1α increased the activity of the CYP7A1 promoter suggested that hypoxia decreased the expression of CYP7A1 in a HIF-1-independent manner. Thus, the results of this study suggested that hypoxia decreased the activity of CYP7A1 by limiting its substrate O₂, and by decreasing the transcription of CYP7A1.