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Induction of Angiogenesis by Malarial Infection through Hypoxia Dependent Manner
박미경,고은지,전경윤,김현수,Jin Ok Jo,백경완ㄴ,강윤정,최영현,Yeonchul Hong,Meesun Ock,차희재 대한기생충학ㆍ열대의학회 2019 The Korean Journal of Parasitology Vol.57 No.2
Malarial infection induces tissue hypoxia in the host through destruction of red blood cells. Tissue hypoxia in malarial infection may increase the activity of HIF1α through an intracellular oxygen-sensing pathway. Activation of HIF1α may also induce vascular endothelial growth factor (VEGF) to trigger angiogenesis. To investigate whether malarial infec- tion actually generates hypoxia-induced angiogenesis, we analyzed severity of hypoxia, the expression of hypoxia-related angiogenic factors, and numbers of blood vessels in various tissues infected with Plasmodium berghei. Infection in mice was performed by intraperitoneal injection of 2×106 parasitized red blood cells. After infection, we studied parasitemia and survival. We analyzed hypoxia, numbers of blood vessels, and expression of hypoxia-related angiogenic factors in- cluding VEGF and HIF1α. We used Western blot, immunofluorescence, and immunohistochemistry to analyze various tis- sues from Plasmodium berghei-infected mice. In malaria-infected mice, parasitemia was increased over the duration of infection and directly associated with mortality rate. Expression of VEGF and HIF1α increased with the parasitemia in vari- ous tissues. Additionally, numbers of blood vessels significantly increased in each tissue type of the malaria-infected group compared to the uninfected control group. These results suggest that malarial infection in mice activates hypoxia- induced angiogenesis by stimulation of HIF1α and VEGF in various tissues.
Kim, Jieun,Wang, Sihyung,Lee, Chanbin,Sung, Sumi,Shin, Yongbo,Song, Kyoung Seob,Cha, Hee-Jae,Ock, Meesun,Jung, Youngmi S. Karger AG 2018 CELLULAR PHYSIOLOGY AND BIOCHEMISTRY Vol.50 No.4
<P><B><I>Background/Aims:</I></B> Malaria is the most deadly parasitic infection in the world, resulting in damage to various organs, including the liver, of the infected organism; however, the mechanism causing this damage in the liver remains unclear. Liver fibrosis, a major characteristic of liver diseases, occurs in response to liver injury and is regulated by a complex network of signaling pathways. Hedgehog (Hh) signaling orchestrates a number of hepatic responses including hepatic fibrogenesis. Therefore, we investigated whether Hh signaling influenced the liver’s response to malarial infection. <B><I>Methods:</I></B> Eight-week-old male C57BL/6 mice inoculated with blood containing <I>Plasmodium berghei</I> ANKA (<I>Pb</I>A)-infected erythrocytes were sacrificed when the level of parasitemia in the blood reached 10% or 30%, and the livers were collected for biochemical analysis. Liver responses to <I>Pb</I>A infection were examined by hematoxylin and eosin staining, real-time polymerase chain reaction, immunohistochemistry and western blot. <B><I>Results:</I></B> Severe hepatic injury, such as ballooned hepatocytes, sinusoidal dilatation, and infiltrated leukocytes, was evident in the livers of the malaria-infected mice. Hypoxia was also induced in 30% parasitemia group. With the accumulation of Kupffer cells, inflammation markers, TNF-α, interleukin-1β, and chemokine (C-X-C motif) ligand 1, were significantly upregulated in the infected group compared with the control group. Expression of fibrotic markers, including transforming growth factor-β, α-smooth muscle actin (α-SMA), collagen 1a1, thymosin β4, and vimentin, were significantly higher in the infected groups than in the control group. With increased collagen deposition, hepatic stellate cells expressing α-SMA accumulated in the liver of the <I>Pb</I>A-infected mice, whereas those cells were rarely detected in the livers of the control mice. The levels of Hh signaling and Yes-associated protein (YAP), two key regulators for hepatic fibrogenesis, were significantly elevated in the infected groups compared with the control group. Treatment of mice with Hh inhibitor, GDC-0449, reduced hepatic inflammation and fibrogenesis with Hh suppression in <I>Pb</I>A-infected mice. <B><I>Conclusion:</I></B> Our results demonstrate that HSCs are activated in and Hh and YAP signaling are associated with this process, contributing to increased hepatic fibrosis in malaria-infected livers.</P>
Expression and Characterization of α-Methylacyl CoA Racemase from Anisakis simplex Larvae
Bong Jin Kim,Sun Mi Kim,Min Kyung Cho,Hak Sun Yu,Yong Seok Lee,Hee Jae Cha,Meesun Ock 대한기생충학열대의학회 2012 The Korean Journal of Parasitology Vol.50 No.2
Larval excretory-secretory products of Anisakis simplex are known to cause allergic reactions in humans. A cDNA library of A. simplex 3rd-stage larvae (L3) was immunoscreened with polyclonal rabbit serum raised against A. simplex L3 excretory-secretory products to identify an antigen that elicits the immune response. One cDNA clone, designated as α-methylacyl CoA racemase (Amacr) contained a 1,412 bp cDNA transcript with a single open reading frame that encoded 418 amino acids. A. simplex Amacr showed a high degree of homology compared to Amacr orthologs from other species. Amacr mRNA was highly and constitutively expressed regardless of temperature (10-40˚C) and time (24-48 hr). Immunohistochemical analysis revealed that Amacr was expressed mainly in the ventriculus of A. simplex larvae. The Amacr protein produced in large quantities from the ventriculus is probably responsible for many functions in the development and growth of A. simplex larvae.
Analysis of KAP1 expression patterns and human endogenous retrovirus Env proteins in ovarian cancer
Kyung‑Yoon Jeon,Eun‑Ji Ko,Young Lim Oh,Hongbae Kim,Wan Kyu Eo,김아리,Han Gyu Sun,Meesun Ock,Ki Hyung Kim,Hee‑Jae Cha 한국유전학회 2020 Genes & Genomics Vol.42 No.10
Background Human endogenous retroviruses (HERVs) constitute around 8% of the human genome and have important roles in human health and disease, including cancers. Previous studies showed that HERV envelope (Env) proteins are highly expressed in cancer tissues and co-related with cancer progression. KAP1 has been reported to play a key role in regulating retrotransposons, including HERV-K, through epigenetic silencing. Objective The relationship between KAP-1 and HERV Envs expressions was analyzed only in tumor cell lines and has not yet been studied in cancer tissues. In this study, we analyzed the expression patterns and relationship between KAP1 and HERV Env proteins in ovarian cancer tissues. Method The expression patterns of KAP-1 and HERV Env proteins, including HERV-K and HERV-R, were analyzed in ovarian cancer tissue microarrays that contained 80 surgical specimens, including normal ovary and malignant ovarian cancers. Results The expression of HERV-R Env and KAP1 proteins is signifcantly higher in ovarian cancer compared with normal ovary tissues. However, the expression of HERV-K Env did not change signifcantly in cancer tissues. The expression patterns of HERV-K Env and HERV-R Env signifcantly increased in early stages of cancer and KAP1 expression was higher in certain stage and types of cancers. However, the expression of HERV-K Env, HERV-R Env, and KAP1 did not change in diferent age groups. The correlation between the expression of KAP1 and HERV-Env, including HERV-K and HERV-R, was not signifcantly correlated. Conclusions The results of this study showed that there was no signifcant correlation between the expression of KAP1 and HERV Env proteins in ovarian cancer tissues, unlike studies with cell lines in vitro. These results suggest that the actual expression of HERV Env proteins in ovarian cancer tissues may be regulated through various complex factors as well as KAP1.
Su-Min Song,Hae Soo Yun,Dorene Van Bik,Hyun Ha Chang,Sang-Ah Lee,Shin-WooKim,Nam Hee Ryoo,Dong Yeub Eun,이난영,Youn-Kyoung Goo,Yeon-ChulHONG,Meesun Ock,차희재,Dong-Il Chung 대한기생충학ㆍ열대의학회 2019 The Korean Journal of Parasitology Vol.57 No.4
From October 2015 to August 2018, tapeworm proglottids were obtained from 10 patients who were residents of Daegu and Gyeongbuk provinces and had a history of raw beef consumption. Most of them had no overseas travel experience. The gravid proglottids obtained from the 10 cases had 15-20 lateral uterine branches. A part of internal tran- scribed spacer 1 (ITS1) DNA of the 10 cases, amplified by polymerase chain reaction (PCR) and digested with AleI restric- tion enzyme, produced the same band pattern of Taenia saginata, which differentiated from T. asiatica and T. solium. Se- quences of ITS1 and cytochrome c oxidase subunit 1 (cox1) showed higher homology to T. saginata than to T. asiatica and T. solium. Collectively, these 10 cases were identified as T. saginata human infections. As taeniasis is one of the im- portant parasitic diseases in humans, it is necessary to maintain hygienic conditions during livestock farming to avoid public health concerns.