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All Journal HAYATI Journal of Biosciences Microbiology Indonesia Health Science Journal of Indonesia Medical Journal of Indonesia Indonesian Journal of Cancer The Indonesian Biomedical Journal Molecular and Cellular Biomedical Sciences (MCBS) Jurnal Ilmu Kefarmasian Indonesia The New Ropanasuri Journal of Surgery Muhammadiyah Journal of Geriatric Indonesian Journal of Cancer eJournal Kedokteran Indonesia Makara Journal of Science Molekul: Jurnal Ilmiah Kimia
Mohamad Sadikin
Department Of Biochemistry And Molecular Biology, Faculty Of Medicine, Universitas Indonesia, Jakarta
Agriculture, Biological Sciences & Forestry Biochemistry, Genetics & Molecular Biology Chemistry Dentistry Earth & Planetary Sciences Health Professions Immunology & microbiology Materials Science & Nanotechnology Medicine & Pharmacology Neuroscience Nursing Public Health

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Expression of hypoxia inducible factor-1α (HIF-1α) gene and apoptosis in the heart induced by systemic hypoxia Hendrawan, Siufui; Jusman, Sri W.A.; Ferdinal, Frans; Prijanti, Ani R.; Wanandi, Septelia I.; Sadikin, Mohamad
Medical Journal of Indonesia Vol 18, No 2 (2009): April-June
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (436.76 KB) | DOI: 10.13181/mji.v18i2.344

Abstract

Aim This study explored the expression of HIF-1α in hypoxic cardiac muscle in mice, and observed the evidence of apoptosis in hypoxia induced cardiomyocyte.Methods Male Sprague-Dawley rats, were randomized into 7 groups (n = 4 per group): control normoxia group that was exposed to atmospheric oxygen and hypoxia groups that were housed in hypoxic chambers (O2 level 8%) for 1, 3, 7, 14, 21, and 28 days respectively. Animals were sacrificed, hearts were rapidly excised, total RNA was extracted with an mRNA isolation kit and the expression of HIF-1α mRNA was then detected by real-time RT-PCR. Apoptosis was assessed by TUNEL method.Results For rat in hypoxia group, the expression of HIF-1α mRNA in cardiac myocytes was clearly up-regulated compared to the control normoxia group. Further, HIF-1α expression level elevated gradually and reached a peak at 21 days of hypoxia. No cell labeled by the TUNEL method was detected in the control group. Compared with the control group, the apoptotic index was significantly increased in the hypoxia group (P < 0.05). There was no significant correlation between the elevation of HIF-1α mRNA and the elevation of apoptotic index.Conclusion Systemic chronic hypoxia caused the elevation of HIF-1α mRNA and apoptosis in cardiac myocytes. (Med J Indones 2009; 18: 97-101)Keywords: TUNEL, RT-PCR, mRNA, apoptotic index
Gene expression of manganese superoxide dismutase in human glioma cells Hardiany, Novi S.; Sadikin, Mohamad; Wanandi, Septelia I.
Medical Journal of Indonesia Vol 19, No 1 (2010): February
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (850.603 KB) | DOI: 10.13181/mji.v19i1.379

Abstract

Aim This study analyze the MnSOD gene expression as endogenous antioxidant in human glioma cells compared with leucocyte cells as control.Methods MnSOD gene expression of 20 glioma patients was analyzed by measuring the relative expression of mRNA and enzyme activity of MnSOD in brain and leucocyte cells. The relative expression of mRNA MnSOD was determined by using quantitative Real Time RT-PCR and the enzyme activity of MnSOD using biochemical kit assay (xantine oxidase inhibition). Statistic analysis for mRNA and enzyme activity of MnSOD was performed using Kruskal Wallis test.Results mRNA of MnSOD in glioma cells of 70% sample was 0.015–0.627 lower, 10% was 1.002-1.059 and 20% was 1.409-6.915 higher than in leucocyte cells. Also the specific activity of MnSOD enzyme in glioma cells of 80% sample showed 0,064-0,506 lower and 20% sample was 1.249-2.718 higher than in leucocyte cells.Conclusion MnSOD gene expression in human glioma cells are significantly lower than its expression in leucocytes cells. (Med J Indones 2010; 19:21-5)Keywords : MnSOD, glioma, gene expression
Cytoglobin expression in oxidative stressed liver during systemic chronic normobaric hypoxia and relation with HIF-1α Jusman, Sri W.A.; Iswanti, Febriana C.; Suyatna, Franciscus D.; Ferdinal, Frans; Wanandi, Septelia I.; Sadikin, Mohamad
Medical Journal of Indonesia Vol 23, No 3 (2014): August
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (412.573 KB) | DOI: 10.13181/mji.v23i3.1025

Abstract

Background: Liver is sensitive against hypoxia and hypoxia will stabilize HIF-1α. At the same time, hypoxia will produce reactive oxygen species (ROS) which can be scavenged by Cygb. The purpose of our study is to know, if normobaric hypoxia can induce Cygb expression and its association with HIF-1α stabilization.Methods: This is an experimental study using 28 male Sprague-Dawley rats, 150-200 g weight. Rats are divided into 7 groups: control group and treatment groups that are kept in hypoxic chamber (10% O2: 90% N2) for 6 hours, 1, 2, 3, 7 and 14 days. All rats are euthanized after treatment and liver tissue are isolated, homogenized and analyzed for oxidative stress parameter, expression of Cygb and HIF-1α.Results: Expression of Cygb mRNA and protein was increased on the day-1 after treatment and reach the maximum expression on the day-2 of hypoxia treatment. But, the expression was decreased after the day-3 and slightly increased at the day-14 of hypoxia. The correlation between expression of Cygb and oxidative stress parameter was strongly correlated. Cygb mRNA, as well as protein, showed the same kinetic as the HIF-1, all increased about day-1 and day-2.Conclusion: Systemic chronic hypoxia and/or oxidative stress up-regulated HIF-1α mRNA which is correlated with the Cygb mRNA and protein expression. Cygb mRNA as well as Cygb protein showed the same kinetic as the HIF-1, all increased about day-1 and day-2 suggesting that Cygb could be under the regulation of HIF-1, but could be controlled also by other factor than HIF-1.
Expression of manganese superoxide dismutase in rat blood, heart and brain during induced systemic hypoxia Wanandi, Septelia I.; Dewi, Syarifah; Jusman, Sri W.A.; Sadikin, Mohamad
Medical Journal of Indonesia Vol 20, No 1 (2011): February
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (242.847 KB) | DOI: 10.13181/mji.v20i1.421

Abstract

Background: Hypoxia results in an increased generation of ROS. Until now, little is known about the role of MnSOD - a major endogenous antioxidant enzyme - on the cell adaptation response against hypoxia. The aim of this study was to  determine the MnSOD mRNA expression and levels of specific activity in blood, heart and brain of rats during induced systemic hypoxia.Methods: Twenty-five male Sprague Dawley rats were subjected to systemic hypoxia in an hypoxic chamber (at 8-10% O2) for 0, 1, 7, 14 and 21 days, respectively. The mRNA relative expression of MnSOD was analyzed using Real Time RT-PCR. MnSOD specific activity was determined using xanthine oxidase inhibition assay.Results: The MnSOD mRNA relative expression in rat blood and heart was decreased during early induced systemic hypoxia (day 1) and increased as hypoxia continued, whereas the mRNA expression in brain was increased since day 1 and reached its maximum level at day 7. The result of MnSOD specific activity during early systemic hypoxia was similar to the mRNA expression. Under very late hypoxic condition (day 21), MnSOD specific activity in blood, heart and brain was significantly decreased. We demonstrate a positive correlation between MnSOD mRNA expression and specific activity in these 3 tissues during day 0-14 of induced systemic hypoxia. Furthermore, mRNA expression and specific activity levels in heart strongly correlate with those in blood.Conclusion: The MnSOD expression at early and late phases of induced systemic hypoxia is distinctly regulated. The MnSOD expression in brain differs from that in blood and heart revealing that brain tissue can  possibly survive better from induced systemic hypoxia than heart and blood. The determination of MnSOD expression in blood can be used to describe its expression in heart under systemic hypoxic condition. (Med J Indones 2011; 20:27-33)Keywords: MnSOD, mRNA expression, ROS, specific activity, systemic hypoxia
Schizonticidal effect of a combination of Amaranthus spinosus L. and Andrographis paniculata Burm. f./Nees extracts in Plasmodium berghei-infected mice Susantiningsih, Tiwuk; Ridwan, Rahmawati; Prijanti, Ani R.; Sadikin, Mohamad; Freisleben, Hans-Joachim
Medical Journal of Indonesia Vol 21, No 2 (2012): May
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (562.029 KB) | DOI: 10.13181/mji.v21i2.482

Abstract

Background: Amaranthus spinosus and Andrographis paniculata are traditionally used as antimalarial herbs, but the combination of both has not yet been tested. The aim of this study was to determine the schizonticidal anti-malaria effect of a combination in Plasmodium berghei-infected mice.Methods: Male mice (Balb/c strain) weighing 28-30 g, 7-8 weeks old, were randomly devided into 5 groups of 4 animals each. Group A: controls (nil) and 4 treatment groups (B, C, D, and E). Group B: Amarathus 10 mg/kgBW, group C: Andrographis 2 mg/kgBW, group D: combination of Amaranthus + Andrographis 10 mg + 2 mg/kgBW. All treatment with plant extracts was administered orally, once per day for 7 days. Group E was given chloroquine 10 mg/kgBW, once a day orally, for 3 days.Results: The body weigh increased only in group D, hemoglobin concentration increased significantly vs controls (p < 0.05) in treatment groups C, D, and E, and blood schizonticidal activity was seen in all treatment groups, highest at almost 90% in groups D and E. Survival rate was 100% in all groups.Conclusion: The combination of Amaranthus and Andrographis (10 mg + 2 mg/kgBW) exerts the same blood schizonticidal activity as chloroquine 10 mg/kgBW. (Med J Indones. 2012;21:66-70)Keywords: Amaranthus spinosus, Andrographis paniculata, Balb/c mice, Plasmodium berghei, schizonticidal effect
Effect of hypoxia-inducible factor-1α induction by CoCl2 on breast cancer cells survival: influence of cytochrome-c and survivin Paramita, Reni; Sadikin, Mohamad; Sutandyo, Noorwati; Wanandi, Septelia I.
Medical Journal of Indonesia Vol 23, No 3 (2014): August
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (596.052 KB) | DOI: 10.13181/mji.v23i3.933

Abstract

Background: Tumor tissue usually became hypoxic due to disruption of oxygen supply. Adaptation response to hypoxia is mediated by transcription factor, hypoxia- inducible factor-1α (HIF-1α). HIF-1α signaling is known to increase the expression of pro-apoptotic protein cytochrome-c, and anti- apoptotic survivin. In this study we wanted to analyze the role of HIF-1α on breast cancer cells survival through pro-apoptosis cytohrome-c and anti-apoptosis survivin regulation.Methods: Breast cancer cell lines T47D were induced by CoCl2 then harvested to analyze the expression of HIF-1α, protein cytochrome-c, mRNA survivin and cell viabilities.Results: HIF-1α induction by CoCl2 causes the increase of  protein and mRNA of HIF-1α, cytochrome-c protein, and survivin mRNA, but does not cause the changes in cell viability.Conclusion: HIF-1α induction have no effects on breast cancer cell line T47D viabilities due to the balance regulation between pro-apoptosis expression cytochrome-c and anti-apoptosis survivin.
IFNγ modulates human immunoglobulin receptor expression in lipoaspirate-derived mesenchymal stem cells Laksmitawati, Dian R.; Pawitan, Jeanne A.; Sadikin, Mohamad; Sardjono, Caroline T.; Utomo, Ahmad R.
Medical Journal of Indonesia Vol 23, No 3 (2014): August
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (576.473 KB) | DOI: 10.13181/mji.v23i3.923

Abstract

Background: Mesenchymal stem cell (MSC) has been reported to have immunomodulator capacity against autoimmune diseases and to prevent allogenic tissue rejection. Many studies revealed that MSC’s inhibit T cell proliferation and induce immunosuppressive condition through the production of prostaglandins, and interleukin-10. In addition, MSC was reported to reduce circulating autoantibody in autoimmune patients following MSC transfusion. So far, there has been no report stating the presence of Fc receptors (receptors for immunoglobulin) on MSCs. The aim of this study was to reveal the expression of FcγRs in lipoaspirate-derived MSCs by measuring transcription of FcγR mRNA and whether the expression can be modulated.Methods: Lipoaspirate-derived MSCs were cultured in suitable medium and confirmed to be MSCs according to the criteria published by International Society for Cellular Therapy. Total mRNA of MSCs was isolated, and detection of human FcγRI, FcγRIIA and FcγRIIB mRNA was performed. Further, modulation of the expression was tested using heat aggregated gamma globulin (HAGG) and interferon (IFN)γ.Results: FcγRs mRNA was detected in the first passage of MSCs. However, the expression was no longer present after more than 4 passages. Further, increased level of FcγRI and FcγRIIA mRNA expression was detected with the addition of IFNγ in the culture. This preliminary finding opens a new insight for the understanding of interaction between MSCs and immunoglobulin G through FcγRs.Conclusion: Lipoaspirate-derived MSCs express FcγRs, and the expression is modulated by IFNγ.
Correlation of hypoxia inducible factor-1α and vascular endothelium growth factor in rat myocardium during aerobic and anaerobic exercise Flora, Rostika; Freisleben, Hans-Joachim; Ferdinal, Frans; Wanandi, Septelia I.; Sadikin, Mohamad
Medical Journal of Indonesia Vol 21, No 3 (2012): August
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (837.72 KB) | DOI: 10.13181/mji.v21i3.493

Abstract

Background: Exercise increases the need for oxygen to generate ATP through oxidative phosphorylation. If the high energy demand during exercise is not balanced by sufficient oxygen supply, hypoxia occurs in skeletal muscle tissue leading to upregulation of hypoxia inducible factor-1α (HIF-1α). The activity of HIF-1α increases the expression of various genes in order to reduce the metabolic dependence on oxygen and to increase oxygen supply to the tissue, e.g., VEGF which plays a role in angiogenesis. In myocardium, it is unclear whether exercise leads to hypoxia and whether HIF-1α and VEGF play a role in the mechanism of hypoxic adaptation. This study aimed to investigate the correlation of HIF-1α and VEGF in heart muscle tissue of rats during aerobic and anaerobic exercise.Methods: A rat treadmill was used with a specific exercise program for 1, 3, 7 and 10 days. The concentrations of HIF-1α and VEGF were measured the myocardium.Results: Both, HIF-1α protein and VEGF were increased (p < 0.05) in the groups with aerobic and anaerobic exercise. Concentrations of HIF-1α were highest on the first day of activity, being higher in the anaerobic than in the aerobic group (156.8 ± 33.1 vs. 116.03 ± 5.66). Likewise, the highest concentration of VEGF in the group with anaerobic exercise occurred on the first day (36.37 ± 2:35), while in the aerobic group, VEGF concentration was highest on day 3 (40.66 ± 1.73). The correlation between the myocardial tissue consentrations of HIF-1α and VEGF is moderate (r = 0.59) in the aerobic group and strong in the anaerobic group (r = 0.69).Conclusion: Aerobic and anaerobic exercise increase HIF-1α and VEGF concentrations in rat myocardium in specific patterns. The anaerobic condition triggers vascularization stronger and obviously earlier than aerobic exercise. (Med J Indones. 2012;21:133-40)Keywords: Exercise, HIF-1α, myocardium, VEGF
Ekspresi Relatif mRNA Hypoxia Inducible Factor-1? pada Sel Glioma Penderita Hardiany, Novi Silvia; Sadikin, Mohamad; Wanandi, Septelia Inawati
Indonesian Journal of Cancer Vol 7, No 1 (2013): Jan - Mar 2013
Publisher : "Dharmais" Cancer Center Hospital

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (530.441 KB)

Abstract

Glioma merupakan tumor otak primer yang cukup sering ditemukan di Indonesia di antara keganasan otak lainnya. Penderita glioma mempunyai angka harapan hidup yang rendah dikarenakan seringnya mengalami resistansi terapi. Hipoksia merupakan salah satu faktor yang mempengaruhi respons terapi radiasi. Penelitian ini menganalisis ekpresi mRNA HIF-1?, sebagai petanda jaringan hipoksia, pada glioma derajat rendah dibandingkan dengan glioma derajat tinggi. Sampel terdiri dari 15 jaringan glioma derajat rendah, 6 jaringan glioma derajat tinggi, dan 21 sel lekosit dari penderita glioma sebagai kontrol sel normal. Ekspresi relatif mRNA HIF-1? ditentukan secara kuantitatif dengan menggunakan Real Time RT-PCR. Hasil penelitian menunjukkan bahwa ekspresi mRNA HIF-1? pada glioma derajat tinggi lebih tinggi dibandingkan dengan glioma derajat rendah, namun tidak bermakna secara statistik. Hal yang menarik yaitu ditemukan peningkatan ekspresi mRNA HIF-1? dengan nilai yang bervariasi pada 73 % sampel glioma derajat rendah dibandingkan dengan sel lekosit sebagai kontrol sel normal. Begitu juga pada glioma derajat tinggi ditemukan peningkatan mRNA HIF-1? dengan nilai yang bervariasi pada 100% sampel. Dengan demikian, dapat disimpulkan bahwa terdapat variasi derajat hipoksia pada glioma derajat rendah dan derajat tinggi yang mungkin mempengaruhi keberhasilan terapi radiasi.Kata kunci: Glioma, mRNA HIF-1?, hipoksia
Gene expression and enzyme activities of carbonic anhydrase and glutaminase in rat kidneys induced by chronic systemic hypoxia Syarifin, Andi N.K.; Jusman, Sri W.A.; Sadikin, Mohamad
Medical Journal of Indonesia Vol 24, No 3 (2015): September
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (527.008 KB) | DOI: 10.13181/mji.v24i3.1190

Abstract

Background: Hypoxia can cause acidosis. Kidney plays an essential role in maintaining acid-base balance, which involves the activities of carbonic anhydrase (CA) and glutaminase (GLS). This study is aimed to determine the expression and activities of the CA9 and GLS1 enzymes in relation to hypoxia inducible factor-1α (HIF-1α), a transcription factor protein which is a marker of hypoxia.Methods: This study was an in vivo experimental study with coupled paralel design. used 25 male Sprague-Dawley rats weighing 150-200 g. Rats were divided into 5 groups: the control group (normoxic condition) and 4 treatment groups. The latter were kept in a hypoxic chamber (10% O2: 90% N2) for 1, 3, 5 and 7 days. All rats were euthanized after treatment, kidneys excised, tissues homogenized and investigated for gene expression of CA9, GLS1 and HIF-1α. On protein level, total enzymatic activities of CA and GLS and protein of HIF-1α were also investigated. Data were analyzed statistically using ANOVA for significance, and as its alternative, used Mann-Whitney and Kruskal-Wallis test.Results: Results showed that HIF-1α mRNA increased during hypoxia, but not HIF-1α protein. It seemed that acidosis occurs in kidney tissue, indicated by increased CA9 and GLS1 mRNA expression and specific activity of total CA and GLS1. Expression of CA9 and GLS1 mRNA both showed strong positive correlation with HIF-1α mRNA, but not with HIF-1α protein.Conclusion: It is suggested that during chronic systemic hypoxia, gene expression of CA9 and GLS1 and their enzyme activities were increased as a response to acidosis and related with the expression of HIF-1α mRNA.
Co-Authors . Rusdi Ahmad A. Jusuf Ahmad Aulia Ahmad Aulia Jusuf Ahmad R. Utomo AMARILA MALIK Amarila Malik Andi N.K. Syarifin, Andi N.K. ANDREW ROBERT COSSINS Angelina Stevany Regina Masengi Ani R. Prijanti Arief Budi Witarto Aryenti . Asri Rasad ASTUTIATI NURHASANAH Astutiati Nurhasanah Bethy S. Hernowo Caroline T. Sardjono CAROLINE TAN SARDJONO Cicia Firakania, Cicia DARYL ROBERT WILLIAMS Dewi Sukmawati Diah Iskandriati Dian R. Laksmitawati Dian Ratih Laksmitawati Dwirini Retno Gunarti Ekawati, Maria Erni Hernawati Purwaningsih, Erni Hernawati Fanny Septiani Farhan Febriana C. Iswanti Febriana Catur Iswanti Franciscus D. Suyatna Frans Ferdinal HANIFAH RAHMI Hans -Joachim Freisleben Hans Joachim Freisleben HANS-JOACHIM FREISLEBEN Heri Wibowo Hermansyah Hermansyah Indra G. Mansur Jeanne A. Pawitan JEANNE ADIWINATA PAWITAN Juniarti . Jusman, Sri Widia Azraki Lailan Safina Nasution Lio, Tiara Mayang Pratiwi Mohamad Saekhu Muchlis Ramli Nani Dharmasetiawani Nina Fitriana, Nina Ninik Mudjihartini Noorwati Sutandyo Novi S. Hardiany Novi Silvia Hardiany Nurhadi Ibrahim Nurjati C. Siregar Oentoeng Soeradi Pamungkas, Joko Praditi, Citra Radiana D. Antarianto Rahmawati Ridwan Reni Paramita Rini Puspitaningrum RONDANG ROEMIATI SOEGIANTO Rostika Flora Saleh, Mgs. M. Irsan Samsuridjal Djauzi Sari, Dewi H. Sarsanti, Pungguri Ayu Nega Satriotomo, Irawan Septelia I. Wanandi SEPTELIA INAWATI WANANDI SEPTELIA INAWATI WANANDI Siregar, Nurjati Siti Rahmawati Achyat Siufui Hendrawan Sri S. Ningsih, Sri S. Sri W.A. Jusman Sri Widia A.Jusman Subandrate Syarifah Dewi Tiwuk Susantiningsih Tomohiko Yamazaki TRISMILAH TRISMILAH Trismilah Trismilah Trismilah, Uly A. Nikmah, Uly A. Wahono Sumaryono Wardaya Wardaya Wawan Mulyawan Wawan Mulyawan Yefta Moenadjat Yudianita Kesuma, Yudianita Yuhernita . Zen Hafy