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Siti Rahmawati Achyat
Abstrak :
Pada keadaan hipoksia sel aksn berganti metabolisme dari tipe aerob Ire tipe yang lebih anaerob, yang lebih sedikit menghasilkan energi. Untuk memenuhi kebutuhan energi yang sama, set pada keadaan hipoksia meningkatkan konsurnsi glukosa. Penelitian ini bertuju.an untuk mengetahui gambaran adaptasi metabolisme otot pada tikus yang dibuat hipoksia dibandingkan dengan penyu hijau (Chelonia mydas). Penyu bijau merupakan hewan yang bernafas dtngan paru-paru namun dapat berakti.vitas lama di bawah air laut. Sejumiah tikus ditempatkan pada kandang hipoksia (tekanan l atm,dan kandungan o, 10%) selama I, 7 14, dan 21 hari. Pada akhir periode hipoksia setelah euthanasia. otot dianalisis untuk pengukuran konsumsi glaktivitas spesifik LDH dan etektroforesis isozim LDH. Analisis yang sarna juga di1akukan pada penyu yang ditempatkan pada kondisi nonnoksia. Konsumsi glukosa dan aktivitas LDH meningkat sejalan dengan lamanya hipoksia pada otot tikus, sedangkan isozim LDH tidak mengalami pcrubahan po1a.; kecuali peningka:tan LDH 4 dan LDH 5. Konsumsi glukosa dan aktivitas spesifik LDH otot penyu Iebih. tinggi dibanding otot tikus dan hanya terdapat satu tipe isozim LDH yaitu LDH 4 yang merupakan isozim LDH anaerob. Hasil penelitian menunjukkan adaptasi sel otot terhadap hipoksia, dengan mengubah metabolisme aerob menjadi lebih anaerob.
During hyPOxia, there is a shift ftom aerobic to anaerobic metabolism which results in the production of less ATP. 1n order to meet the same energy needed, the hypoxic cells have to increase the glucose consumption rate. In this study, we described the muscle metabolic adaptation in globally hypoxic rats as wcU a<;. in sea turtles (Chelonia mydm), the latter animals are well known as lung breathing species which spend most of their time under sea water. Rats were placed in a hypoxic chamber (I atrn, 0, l 0 Va! %) for I, 7, 14 and 21 days. At the end of each period, after euthanasia their muscles were analyzed for glucose metabolism rate, total specific LDH activities and LDH isozymes electrQphoresis. The same a!lalysis was made in sea turtle muscles which were placed in normal condition. Glucose consumption rates and LDH activities increased proportionally with the duration of hypoxic state in rats, whereas for LDH isozymes. there were no any change in pattern except for LDH 4 and LDH 5, which was more prominent the course of hypoxia. On the other hand, even in normoxic condition, sea turtles muscles consumed higher amountĀ·of glucose. showed much higher of total specific LDH activities and had only one type of LDH isoZ)'Ule, i.e. LDH 4, which is anaerobic isozyme of LDH.The results suggest that during adaptation to hypoxia, the metabolism of aerobic muscle of rat switch to more anaerobic pattern and that sea turtle was genetlcally set fur hypo-xia condition.
Depok: Universitas Indonesia, 2010
T31649
UI - Tesis Open  Universitas Indonesia Library
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Titta Novianti
Abstrak :
Latar Belakang: Pada proses regenerasi jaringan terjadi ketidakseimbangan antara kebutuhan oksigen dengan suplai oksigen yang menyebabkan jaringan mengalami hipoksia relatif. Keadaan hipoksia diduga memiliki peran penting dalam proses regenerasi jaringan. Pada penelitian ini, dianalisis ekspresi protein dan gen yang berperan mengatasi keadaan hipoksia (HIF-1α dan HIF-2α), protein yang berperan dalam suplai oksigen (Cygb), protein yang menstimulasi biogenesis mitokondria (PGC-1α) serta enzim yang mampu menangkal radikal bebas (MnSOD) pada regenerasi jaringan. Regenerasi jaringan ekor pada cecak rumah (Hemidactylus platyurus) digunakan sebagai model dalam penelitian ini, karena merupakan hewan yang paling dekat secara taksonomi dengan mamalia yang memiliki daya regenerasi tinggi, dibandingkan vertebrata lain dengan kemampuan sama. Diharapkan penelitian ini dapat menjadi model dalam mempelajari proses regenerasi dalam upaya pengembangan terapi penyembuhan luka. Metode: Penelitian bersifat eksperimental deskriptif menggunakan jaringan 30 ekor cecak hasil regenerasi pada hari ke 1; 3; 5; 8; 10; 13; 17; 21; 25; dan 30 setelah autotomi dengan 3 kali pengulangan pada setiap pengamatan. Cecak diperoleh dari lingkungan laboratorium Zoologi Puslit Biologi LIPI Cibinong. Analisis ekspresi gen dilakukan dengan metoda qRT-PCR; analisis ekspresi protein dinilai dengan metoda Western Blot dan imunohistokimia, serta dilakukan analisis struktur histologi jaringan dengan pewarnaan hematoksilin-eosin. Penelitian dilakukan di Laboratorium Departemen Biokimia & Biologi Molekuler FKUI; laboratorium Histologi FKUI, laboratorium PRVKP FKUI, dan laboratorium Patologi Anatomi FKH IPB. Penelitian dalam kurun waktu tahun 2015-2018. Hasil penelitian: Grafik pertumbuhan jaringan ekor cecak menghasilkan pola pertumbuhan yang lambat pada 13 hari pertama, pertumbuhan yang sangat cepat hari ke 13 sampai ke 21, dan kembali lambat sampai hari ke 30. Pada awal pertumbuhan, ekspresi HIF-1α dan HIF-2α tinggi menunjukkan jaringan dalam keadaan hipoksia. Tingginya ekspresi Cygb selama proses regenerasi jaringan dari awal hingga akhir pengamatan menunjukkan perannya untuk mengakomodasi oksigen selama proses regenerasi berlangsung. Ekspresi PGC-1α yang tinggi di awal proses dan tetap dipertahankan sampai akhir pengamatan berperan untuk mempertahankan agar energi untuk proses regenerasi dapat terpenuhi melalui biogenesis mitokondria. Tingginya ekspresi MnSOD dalam jaringan pada awal regenerasi diduga memiliki peranan yang berkaitan dengan netralisasi senyawa radikal dalam jaringan. Kesimpulan: HIF 1α, HIF 2α, Cygb, PGC 1α dan MnSOD masing-masing memiliki peran penting tersendiri dalam proses regenerasi jaringan.
Background: In tissue regeneration there is an imbalance between oxygen demand and supply causes the tissue to experience relative hypoxia. Hypoxia is thought to have an important role in the tissue regeneration. This research analyzed the expression of proteins and genes that play role in overcoming hypoxia (HIF-1α dan HIF-2α); the protein involved in oxygen supply (Cygb); the protein that stimulates mitochondrial biogenesis (PGC-1α); and the enzyme counteract free radicals (MnSOD). The regeneration of house gecko's tail (Hemidactylus platyurus) was used as a model in this research, because it is the taxonomically closest animal to mammals that have a high capability in regeneration, compared to other vertebrates with the same ability. Hence, this study might become a model in studying tissue regeneration as an effort in developing a wound healing treatment. Method: The research was performed in a descriptive experimental way, using 30 geckos, having undergone regeneration on day 1; 3; 5; 8; 10; 13; 17; 21; 25; and 30 after autotomy. The experiment used 3 repetitions for each observation. House geckos were obtained from the laboratory building of Zoology Research Center of Indonesian Institute of Sciences (LIPI) Cibinong and its surrounding area. The analysis for gene expression was performed using qRT-PCR method; the analysis for protein expression was undertaken using Western Blot method and immunohistochemistry. In addition to these, the structure analysis for the tissue histology was performed using Haematoxilyn and Eosin (H&E) staining method. The study was conducted in the Laboratory of the Department of Molecular Biochemistry & Biology FKUI; Laboratory of the Department of Histology FKUI; laboratory of the Institute of Human Virology & Cancer Biology FKUI; and laboratoty of Phatology Anatomy of Animal Medicine, Institute of Agriculture Bogor, in the year 2015-2018. Results: The graph for the growth of the gecko tail tissue exhibits a slow growth pattern for the first 13 days, followed by a very swift growth between day 13 to 21, returning to slow growth afterwards until day 30. In the early growth stage, the expression of HIF1α and HIF-2α were increased which showed the tissue was in hypoxia state. HIF protein regulates the contributing to the tissue regeneration process, leading to the increasing growth of tissue with the correlation values of r=-0,853 for HIF-1α; r=-0,75 The substantial expression of Cygb observed throughout the process of tissue regeneration indicates its role in accommodating oxygen in the regeneration process. The expression of PGC-1α was observed to be high in the early stages of the process and remain so until the process ends. This indicates its function in maintaining that sufficient energy provided by mitochondrial biogenesis is available for the regeneration process. The high level of MnSOD expression in the tissue in the early stage of regeneration is thought to relate to its role in neutralizing radicals inside the tissue. Conclusion: HIF 1α, HIF 2α, Cygb, PGC 1α and MnSOD have their own important roles in the tissue regeneration process.
Depok: Fakultas Kedokteran Universitas Indonesia, 2018
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UI - Disertasi Membership  Universitas Indonesia Library
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Muhammad Irfannuddin
Abstrak :
Olahraga aerobik terbukti mampu meningkatkan struktur dan fungsi kognitif. Data tentang jenis olahraga aerobik yang terbaik untuk menjaga keseimbangan oksidatif, serta memicu angiogenesis dan neuroplastisitas di berbagai regio otak masih terbatas. Penelitian ini menganalisis pengaruh olahraga aerobik halang rintang terhadap kadar neuroglobin otak, protein pemicu angiogenesis, neuroplastisitas di hipokampus dan korteks prefrontal, serta fungsi memori relasional. Mencit Mus musculus CBS-Swiss strain jantan berusia 10 bulan dilatih berlari di roda berjalan yang diberi halang rintang, berlari dengan kecepatan 10 m/menit, 30 menit/hari, 5 hari/minggu sambil melewati halang rintang untuk setiap 78 cm. Tiga jenis halang rintang diganti setiap 3 hari. Kelompok pembanding adalah mencit yang berlari dengan kecepatan dan waktu yang sama, namun tanpa halang rintang, serta kelompok kontrol yang tidak berolahraga. Kadar neuroglobin otak tidak berbeda bermakna pada tiga kelompok mencit. Latihan lari halang rintang memberikan efek lebih baik dibanding lari tanpa halang rintang pada kadar developmentally regulated brain protein-A (drebrin-A) di hipokampus. Kedua kelompok olahraga memiliki efek yang lebih baik dibanding kontrol pada ekspresi vascular endothelial growth factors (VEGF), kadar drebrin-A, dan paired associative cognitive test. Olahraga aerobik kompleks memicu neuroplastisitas yang lebih baik dibanding aerobik sederhana di hipokampus. Kedua tipe olahraga aerobik mampu meningkatkan angiogenesis dan neuroplastisitas di otak, dan meningkatkan kemampuan memori relasional. Olahraga aerobik tidak meningkatkan kadar neuroglobin secara bermakna. Hal ini menunjukkan bahwa intensitas olahraga aerobik memberikan efek hipoksia yang dapat ditoleransi oleh jaringan otak. ...... Aerobic exercise has been proven to improve of cognitive structure and function. Study about the type of aerobic exercise affects on angiogenesis, neuroplasticity and oxidative homeostasis in brain?s specific regions is still limited. The present study was conducted to investigate the effects of hurdle aerobic exercise on brain neuroglobin level, angiogenesis and neuroplasticity proteins in hippocampus and prefrontal cortex, and relational memory among middle aged CBS-Swiss strain mice. Mice, age 10 months were subjected to hurdle running wheel for 8 weeks. They ran at speed of 10 m/min, 30 min/day, and 5 days/week with hurdles for every 78 cm. Three types of hurdles were changed for every 3 days. Another group of same age mice ran at same speed, time, and period, without hurdle as comparison, while other control group never exercises. The hurdle group exercise has significant higher level of developmentally regulated brain protein-A (drebrin- A) in hippocampus compared to non-hurdle group. Both of exercise groups have significant higher ability on paired associative cognitive test, and they have significant higher expression of vascular endothelial growth factor (VEGF) and higher level of drebrin-A compared to control. Neuroglobin level was not significant different among of all groups. More complex aerobic exercise has better effect on hippocampus neuroplasticity. Both of aerobic exercise has better effect on angiogenesis and neuroplasticity in the brain, and also on cognitive function. Aerobic exercise does not resulting high hypoxic stress and could be tolerated by brain.
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2015
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UI - Disertasi Membership  Universitas Indonesia Library
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Ninik Mudjihartini
Abstrak :
[ABSTRAK
Hipoksia berperan penting pada patofisiologi berbagai penyakit utama penyebab kematian seperti, penyakit jantung iskemia, strok, kanker, penyakit paru kronik, dan gagal jantung kongestif. Kedua protein golongan globin di otak, yaitu neuroglobin (Ngb) dan sitoglobin (Cygb) diduga berperan dalam suplai oksigen ke mitokondria dan melindungi jaringan otak dari kerusakan akibat hipoksia (neuroprotektan). Perubahan ekspresi protein merupakan salah satu bentuk adaptasi biokimia yang penting terhadap perubahan homeostasis. Oleh karena itu timbul pertanyaan bagaimana pola ekspresi Ngb dan Cygb serta peran neuroprotektan kedua protein tersebut di otak pada keadaan hipoksia sistemik kronik (HSK). Penelitian bertujuan manganalisis perbedaan pola ekspresi Ngb dan Cygb serta kaitannya dengan apoptosis pada HSK. Parameter yang diukur adalah Ngb, Cygb, sitokrom c, MDA, GSH dan HIF-lα. Rancangan penelitian yang digunakan adalah studi eksperimental in vivo model HSK pada tikus. Tikus sebagai hewan coba dibagi secara acak dalam 6 kelompok perlakuan, yaitu kelompok I adalah kelompok kontrol atau tanpa perlakuan hipoksia, sedangkan kelompok II, III, IV, V, dan VI mendapat perlakuan hipoksia dengan lama waktu hipoksia selama 1, 3, 5, 7, dan 14 hari. Parameter yang diperiksa meliputi ekspresi Ngb dan Cygb dengan teknik real time-RT PCR, ELISA dan imunofluoresen FITC, stres oksidatif, HIF-1α sebagai penanda hipoksia, dan sitokrom c sebagai penanda apoptosis. Hasil yang diperoleh HSK meningkatkan ekspresi mRNA Ngb pada hipoksia 3, 5, dan 7 hari, namun ekspresi proteinnya menurun pada hipoksia 1, 3, 5, 7, dan 14 hari dibanding dengan kontrol. Berbeda dengan ekspresi mRNA Cygb yang menurun selama hipoksia 1, 3, 5, 7, dan 14 hari, namun protein Cygb meningkat pada hipoksia 1, 3, 5, 7, dan 14 hari dibandingkan dengan kontrol. Korelasi Ngb dengan sitokrom c lemah tidak signifikan, sedangkan Cygb sangat lemah dan tidak signifikan. HSK menginduksi ekspresi HIF-lα yang meningkat tertinggi pada hipoksia 7 hari, dan menyebabkan stres oksidatif yang ditandai dengan meningkatnya MDA pada hipoksia 1, 3 dan 5 hari, serta menurunnya GSH pada hipoksia 1, 3, dan 5 hari. Penelitian ini membuktikan bahwa terdapat perbedaan pola ekspresi Ngb dan Cygb pada HSK. Ekspresi Ngb sebagai respons adaptasi terjadi lebih awal dan lebih dipengaruhi oleh lama waktu hipoksia dibandingkan dengan ekspresi Cygb. Meskipun lemah, Ngb cenderung mempunyai peran menghambat apoptosis dibandingkan dengan protein Cygb.;
ABSTRACT
Hypoxia has an important role in the pathophysiology of high mortality diseases, such as ischemic cardiovascular disease, stroke, cancer, chronic lung disease, and congestive heart failure. The proteins belonged to globin protein group, included neuroglobin (Ngb) and cytoglobin (Cygb), have been presumed to play a role in regulating the oxygen supply into the mitochondria and protecting the brain tissues from damage due to hypoxia (neuroprotectant). An alteration in protein expression due to a homeostatic shift is an important adaptation process in biochemistry. Therefore, the expression pattern of Ngb and Cygb as well as their protein roles in brain during a chronic systemic hypoxia condition (CSH) remain unclear. This study aim to analyse the differences of the Ngb and Cygb expression patterns, and correlation of both protein to apoptosis in chronic systemic hypoxic condition. Ngb, Cygb, Cytochrome c, MDA, GSH, and HIF-1 α. were examined. An in vivo experimental model of CSH was carried out using rat. The experimental rats were randomly divided into 6 treatment groups, i.e. group I was a control group or without hypoxic condition, groups II, III, IV, V, and VI were treated by hypoxic condition for 1, 3, 5, 7, and 14 days, respectively. The Ngb and Cygb expressions were analysed using real time-RTPCR, ELISA, immunofluorescence with FITC, and the measurement of stress oxidative biomarkers, included HIF-1α as a biomarker of hypoxic condition and cytochrome c as a biomarker of apoptosis. The CSH was increased the mRNA expression of Ngb at 3, 5, and 7 days hypoxic groups, while the protein expression was decreased at 1, 3, 5, 7, and 14 days hypoxic groups compared to control group. The mRNA expression of Cygb was decreased at 1, 3, 5, 7, and 14 days hypoxic groups, whereas the Cygb protein expression was increased at 1, 3, 5, 7, and 14 days hypoxic groups compared to control group. The correlation between Ngb with cytochrome c was weakly statistically insignificant, and Cygb with cytochrome c was statistically insignificant. The CSH induced the HIFlα, which was shown by a high increase at 7 days hypoxic group, as well as stress oxidative which was represented by MDA at 1, 3, and 5 days hypoxic groups, and decreased GSH at 1, 3, and 5 days hypoxic groups. There are differences in expression pattern of Ngb and Cygb in CSH. The expression of Ngb, as an adaptive response, occurs earlier and is more influenced by the duration of hypoxic condition compared to Cygb. Although the correlation is weak, the Ngb seems more likely to inhibit apoptosis compared to Cygb protein;Hypoxia has an important role in the pathophysiology of high mortality diseases, such as ischemic cardiovascular disease, stroke, cancer, chronic lung disease, and congestive heart failure. The proteins belonged to globin protein group, included neuroglobin (Ngb) and cytoglobin (Cygb), have been presumed to play a role in regulating the oxygen supply into the mitochondria and protecting the brain tissues from damage due to hypoxia (neuroprotectant). An alteration in protein expression due to a homeostatic shift is an important adaptation process in biochemistry. Therefore, the expression pattern of Ngb and Cygb as well as their protein roles in brain during a chronic systemic hypoxia condition (CSH) remain unclear. This study aim to analyse the differences of the Ngb and Cygb expression patterns, and correlation of both protein to apoptosis in chronic systemic hypoxic condition. Ngb, Cygb, Cytochrome c, MDA, GSH, and HIF-1 α. were examined. An in vivo experimental model of CSH was carried out using rat. The experimental rats were randomly divided into 6 treatment groups, i.e. group I was a control group or without hypoxic condition, groups II, III, IV, V, and VI were treated by hypoxic condition for 1, 3, 5, 7, and 14 days, respectively. The Ngb and Cygb expressions were analysed using real time-RTPCR, ELISA, immunofluorescence with FITC, and the measurement of stress oxidative biomarkers, included HIF-1α as a biomarker of hypoxic condition and cytochrome c as a biomarker of apoptosis. The CSH was increased the mRNA expression of Ngb at 3, 5, and 7 days hypoxic groups, while the protein expression was decreased at 1, 3, 5, 7, and 14 days hypoxic groups compared to control group. The mRNA expression of Cygb was decreased at 1, 3, 5, 7, and 14 days hypoxic groups, whereas the Cygb protein expression was increased at 1, 3, 5, 7, and 14 days hypoxic groups compared to control group. The correlation between Ngb with cytochrome c was weakly statistically insignificant, and Cygb with cytochrome c was statistically insignificant. The CSH induced the HIFlα, which was shown by a high increase at 7 days hypoxic group, as well as stress oxidative which was represented by MDA at 1, 3, and 5 days hypoxic groups, and decreased GSH at 1, 3, and 5 days hypoxic groups. There are differences in expression pattern of Ngb and Cygb in CSH. The expression of Ngb, as an adaptive response, occurs earlier and is more influenced by the duration of hypoxic condition compared to Cygb. Although the correlation is weak, the Ngb seems more likely to inhibit apoptosis compared to Cygb protein;Hypoxia has an important role in the pathophysiology of high mortality diseases, such as ischemic cardiovascular disease, stroke, cancer, chronic lung disease, and congestive heart failure. The proteins belonged to globin protein group, included neuroglobin (Ngb) and cytoglobin (Cygb), have been presumed to play a role in regulating the oxygen supply into the mitochondria and protecting the brain tissues from damage due to hypoxia (neuroprotectant). An alteration in protein expression due to a homeostatic shift is an important adaptation process in biochemistry. Therefore, the expression pattern of Ngb and Cygb as well as their protein roles in brain during a chronic systemic hypoxia condition (CSH) remain unclear. This study aim to analyse the differences of the Ngb and Cygb expression patterns, and correlation of both protein to apoptosis in chronic systemic hypoxic condition. Ngb, Cygb, Cytochrome c, MDA, GSH, and HIF-1 α. were examined. An in vivo experimental model of CSH was carried out using rat. The experimental rats were randomly divided into 6 treatment groups, i.e. group I was a control group or without hypoxic condition, groups II, III, IV, V, and VI were treated by hypoxic condition for 1, 3, 5, 7, and 14 days, respectively. The Ngb and Cygb expressions were analysed using real time-RTPCR, ELISA, immunofluorescence with FITC, and the measurement of stress oxidative biomarkers, included HIF-1α as a biomarker of hypoxic condition and cytochrome c as a biomarker of apoptosis. The CSH was increased the mRNA expression of Ngb at 3, 5, and 7 days hypoxic groups, while the protein expression was decreased at 1, 3, 5, 7, and 14 days hypoxic groups compared to control group. The mRNA expression of Cygb was decreased at 1, 3, 5, 7, and 14 days hypoxic groups, whereas the Cygb protein expression was increased at 1, 3, 5, 7, and 14 days hypoxic groups compared to control group. The correlation between Ngb with cytochrome c was weakly statistically insignificant, and Cygb with cytochrome c was statistically insignificant. The CSH induced the HIFlα, which was shown by a high increase at 7 days hypoxic group, as well as stress oxidative which was represented by MDA at 1, 3, and 5 days hypoxic groups, and decreased GSH at 1, 3, and 5 days hypoxic groups. There are differences in expression pattern of Ngb and Cygb in CSH. The expression of Ngb, as an adaptive response, occurs earlier and is more influenced by the duration of hypoxic condition compared to Cygb. Although the correlation is weak, the Ngb seems more likely to inhibit apoptosis compared to Cygb protein;Hypoxia has an important role in the pathophysiology of high mortality diseases, such as ischemic cardiovascular disease, stroke, cancer, chronic lung disease, and congestive heart failure. The proteins belonged to globin protein group, included neuroglobin (Ngb) and cytoglobin (Cygb), have been presumed to play a role in regulating the oxygen supply into the mitochondria and protecting the brain tissues from damage due to hypoxia (neuroprotectant). An alteration in protein expression due to a homeostatic shift is an important adaptation process in biochemistry. Therefore, the expression pattern of Ngb and Cygb as well as their protein roles in brain during a chronic systemic hypoxia condition (CSH) remain unclear. This study aim to analyse the differences of the Ngb and Cygb expression patterns, and correlation of both protein to apoptosis in chronic systemic hypoxic condition. Ngb, Cygb, Cytochrome c, MDA, GSH, and HIF-1 α. were examined. An in vivo experimental model of CSH was carried out using rat. The experimental rats were randomly divided into 6 treatment groups, i.e. group I was a control group or without hypoxic condition, groups II, III, IV, V, and VI were treated by hypoxic condition for 1, 3, 5, 7, and 14 days, respectively. The Ngb and Cygb expressions were analysed using real time-RTPCR, ELISA, immunofluorescence with FITC, and the measurement of stress oxidative biomarkers, included HIF-1α as a biomarker of hypoxic condition and cytochrome c as a biomarker of apoptosis. The CSH was increased the mRNA expression of Ngb at 3, 5, and 7 days hypoxic groups, while the protein expression was decreased at 1, 3, 5, 7, and 14 days hypoxic groups compared to control group. The mRNA expression of Cygb was decreased at 1, 3, 5, 7, and 14 days hypoxic groups, whereas the Cygb protein expression was increased at 1, 3, 5, 7, and 14 days hypoxic groups compared to control group. The correlation between Ngb with cytochrome c was weakly statistically insignificant, and Cygb with cytochrome c was statistically insignificant. The CSH induced the HIFlα, which was shown by a high increase at 7 days hypoxic group, as well as stress oxidative which was represented by MDA at 1, 3, and 5 days hypoxic groups, and decreased GSH at 1, 3, and 5 days hypoxic groups. There are differences in expression pattern of Ngb and Cygb in CSH. The expression of Ngb, as an adaptive response, occurs earlier and is more influenced by the duration of hypoxic condition compared to Cygb. Although the correlation is weak, the Ngb seems more likely to inhibit apoptosis compared to Cygb protein, Hypoxia has an important role in the pathophysiology of high mortality diseases, such as ischemic cardiovascular disease, stroke, cancer, chronic lung disease, and congestive heart failure. The proteins belonged to globin protein group, included neuroglobin (Ngb) and cytoglobin (Cygb), have been presumed to play a role in regulating the oxygen supply into the mitochondria and protecting the brain tissues from damage due to hypoxia (neuroprotectant). An alteration in protein expression due to a homeostatic shift is an important adaptation process in biochemistry. Therefore, the expression pattern of Ngb and Cygb as well as their protein roles in brain during a chronic systemic hypoxia condition (CSH) remain unclear. This study aim to analyse the differences of the Ngb and Cygb expression patterns, and correlation of both protein to apoptosis in chronic systemic hypoxic condition. Ngb, Cygb, Cytochrome c, MDA, GSH, and HIF-1 α. were examined. An in vivo experimental model of CSH was carried out using rat. The experimental rats were randomly divided into 6 treatment groups, i.e. group I was a control group or without hypoxic condition, groups II, III, IV, V, and VI were treated by hypoxic condition for 1, 3, 5, 7, and 14 days, respectively. The Ngb and Cygb expressions were analysed using real time-RTPCR, ELISA, immunofluorescence with FITC, and the measurement of stress oxidative biomarkers, included HIF-1α as a biomarker of hypoxic condition and cytochrome c as a biomarker of apoptosis. The CSH was increased the mRNA expression of Ngb at 3, 5, and 7 days hypoxic groups, while the protein expression was decreased at 1, 3, 5, 7, and 14 days hypoxic groups compared to control group. The mRNA expression of Cygb was decreased at 1, 3, 5, 7, and 14 days hypoxic groups, whereas the Cygb protein expression was increased at 1, 3, 5, 7, and 14 days hypoxic groups compared to control group. The correlation between Ngb with cytochrome c was weakly statistically insignificant, and Cygb with cytochrome c was statistically insignificant. The CSH induced the HIFlα, which was shown by a high increase at 7 days hypoxic group, as well as stress oxidative which was represented by MDA at 1, 3, and 5 days hypoxic groups, and decreased GSH at 1, 3, and 5 days hypoxic groups. There are differences in expression pattern of Ngb and Cygb in CSH. The expression of Ngb, as an adaptive response, occurs earlier and is more influenced by the duration of hypoxic condition compared to Cygb. Although the correlation is weak, the Ngb seems more likely to inhibit apoptosis compared to Cygb protein]
2015
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UI - Disertasi Membership  Universitas Indonesia Library