Investigating the expression level of liver alpha-amylase gene by Real time PCR method in the liver tissue of normal and obese mice

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Year: Not Specified University Degree: Master's degree Category: Biology - Environment
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  • Summary of Investigating the expression level of liver alpha-amylase gene by Real time PCR method in the liver tissue of normal and obese mice

    Abstract:

    Introduction and Objectives

    Alpha amylase is an enzyme from the hydrolase family that catalyzes 1-4 alpha glycosidic bonds in polysaccharides and is one of the most important digestive enzymes. The use of alpha-amylase inhibitors (such as green tea) can be useful in weight control, so comparing the level of liver alpha-amylase gene expression between obese and normal mice and the effect of enzyme inhibitors on the gene expression level can contribute to obesity and metabolic syndrome treatment studies. The group (n=8) was divided. The first group was normal mice that did not undergo any treatment. The second group was normal rats that had consumed the aqueous alcoholic extract of green tea (in the amount of 0.2 mg). The third group were rats that received a high-calorie diet, and the fourth group were rats that, in addition to receiving a high-calorie diet, also received green tea (0.2 mg) from the aqueous alcoholic extract. During 8 weeks, in 4 groups, body weight was measured weekly, and after the end of the period, liver tissue was isolated and liver alpha-amylase expression was measured. After RNA isolation and cDNA synthesis, Real time-PCR was performed with a specific primer for the Amy-1 gene. Results

    The mean changes in liver alpha-amylase gene expression in normal obese mice increased compared to normal control mice, and this increase is statistically significant (P value?0.01). Also, the mean changes in alpha gene expression Hepatic amylase decreased in treated obese mice compared to normal obese mice, and this decrease is statistically significant (P value ?0.04). Therefore, it can be said that consuming green tea at the same time as a high-calorie diet has a reducing effect on the increase in liver alpha-amylase gene expression.

    Key words: alpha-amylase, liver, gene expression, obesity, green tea. style="direction: rtl;"> 

     

     

     

     

     

     

     

    1-1-Statement of the problem

    Obesity is known as a great risk to human health. Obesity can increase the risk of cardiovascular diseases (mainly heart disease and stroke), type 2 diabetes, musculoskeletal disorders (especially arthritis) and certain types of cancer (endometrium, breast and colon) (74).

    Generally, carbohydrates are one of the main components of the diet. Carbohydrates must be broken down into monosaccharides before they can be absorbed by the body. This decomposition occurs using two enzymes: amylase and glucosidase (55).

    Therefore, the search for a strong and effective inhibitor of alpha-glucosidase and alpha-amylase has been proposed as a tool for the treatment of obesity and has now become a focus for research. So far, various inhibitors for alpha-amylase have been identified, among which flavonoids can be mentioned, among them Catechins pointed out. Catechin is the active ingredient of green tea (65). Therefore, it is possible that green tea has an inhibitory role for alpha-amylase gene expression.

    In this research, it was intended to use green tea extract as a potential inhibitor of hepatic alpha-amylase gene expression in mice. The use of alpha-amylase inhibitors (green tea) can be useful in weight control, so comparing the level of hepatic alpha-amylase gene expression between obese and normal mice and the effect of enzyme inhibitors on the level of gene expression can help obesity and metabolic syndrome treatment studies.

    1-2-Research objectives

    Investigating the level of hepatic alpha amylase gene expression by Real time PCR method in the liver tissue of normal and obese mice

    - Investigating the effect of green tea on the obesity process of obese and normal mice

    1-3- The main hypotheses of the research

    - Green tea extract has an inhibitory effect on the obesity process of obese mice.

    - The expression of alpha amylase gene in the liver of obese mice is higher than that of normal mice.

    - The expression of alpha-amylase gene in the liver of obese mice treated with green tea is lower than that of untreated obese mice.

    - The expression of alpha-amylase gene in the liver of normal mice treated with green tea is lower than that of untreated normal mice.

    1-4- The aspect of novelty and innovation in Research:

    In all the studied articles, the effect of green tea on enzyme activity has been investigated, while the purpose of this research is to study the effect of aqueous and methanolic extracts of green tea on liver alpha-amylase gene expression by real time PCR method in obese and normal mice.

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    Chapter Two: Overview of Past Studies

     

     

     

     

     

     

     

     

    2-1-Amylase:

    Amylase is an enzyme that breaks down starch into sugar. Amylase in human saliva starts the first chemical process of digestion. Foods that contain high amounts of starch but very little sugar, such as rice and potatoes, taste slightly sweet when chewed in the mouth because amylase in the mouth converts starch to sugar. Also, the amylase in the pancreas hydrolyzes the starch in the diet into disaccharides and trisaccharides, which are converted into glucose by other enzymes to supply the body with energy. Plants and some bacteria also produce amylase (26).

    2-1-1- History:

    Laches in 1831, described the hydrolysis of starch to amylase in saliva due to the presence of an enzyme in saliva called ptyalin or the fermentative substance of saliva (38). In 1833, French chemists separated the amylase complex from barley sprouts and named it "diastase" (53) and in 1862, Jekolowicz identified pancreatic amylase (14). They are energy rich food. Amylase has played a key role in the evolution of the human digestive system because it has allowed humans to use a substitute for fruit and protein. Duplication of pancreatic amylase gene has been developed independently in humans and rodents, which shows the high importance of this enzyme. The level of salivary amylase found in human descendants is six to eight times higher than that of chimpanzees, who are mainly fruit eaters and consume less starchy substances compared to humans (72). style="direction: rtl;"> Introduction and Objectives

    Alpha-amylase catalyzes the hydrolysis of 1,4-alpha-glucosidic linkages in polysaccharides and has three main subtypes: salivary, pancreatic and hepatic.

  • Contents & References of Investigating the expression level of liver alpha-amylase gene by Real time PCR method in the liver tissue of normal and obese mice

    List:

    Abstract: 1

    Chapter 1: General 2

    1-1-Statement of the problem. 3

    1-2- Research objectives. 4

    1-3- The main assumptions of the research. 4

    1-41- The aspect of newness and innovation in research. 4

    Chapter 2: Review of past studies 5

    2-1-Amylase 6

    2-1-1- History. 6

    2-1-2-amylase in human development. 6

    2-1-3- Functions of amylase 7

    2-1-4- Structure of amylase 9

    2-1-5- Measurement of blood level. 9

    2-2-alpha-amylase 10

    2-2-1-function of alpha-amylase 11

    2-2-2-alpha-amylase in human physiology. 12

    2-3- Salivary amylase or Ptyalin 12

    2-3-1- Genetic variation in salivary amylase. 12

    2-4- Pancreatic alpha-amylase 13

    2-5- Alpha-amylase in pathology 13

    2-5-1- Interpretation of alpha-amylase level 13

    2-6- Alpha-amylase limiting buffer 14

    2-7- Enzyme activity study 14

    2-7-1- Alpha-amylase activity measurement methods before the colorimetric method. 14

    2-7-2 - Colorimetric methods: 15

    2-8- Domain architecture of alpha-amylase structure (Domain) 15

    2-9- Alpha-amylase genes in humans 16

    2-10- Alpha-amylase in mice 18

    2-10-1-Difference in the end sequence of 5 mRNAs Hepatic alpha-amylase and rat salivary glands in terms of size 19

    2-10-2- Studies related to analysis of liver alpha-amylase mRAN sequence. 20

    2-10-3-characteristics of hepatic alpha-amylase mRAN. 20

    2-11- alpha-amylase inhibitors 21

    2-11-1- green tea 22

    2-11-2- benefits of green tea 22

    2-11-2-1- prevention of blood clot disease 23

    2-11-2-2- the effect of green tea on people suffering from tri Glyceride. 24

    2-11-2-3-thinning the blood and preventing it from clotting. 24

    2-11-2-4-reducing blood pressure and preventing it. 24

    2-11-2-5-minimizing the amount of damage to the brain and heart. 25

    2-11-2-6-Protection against all types of cancer. 25

    2-11-2-7-prevention of type 2 diabetes. 25

    2-11-2-8-weight loss. 26

    Chapter 3 Materials and Methods 27

    3-1- Working methods: 28

    3-1-1- Laboratory animal under study: 28

    3-1-1-1- The reasons for choosing this animal in brief are: 28

    3-1-1-2-Animal keeping conditions: 28

    3-1-2- The type of study 29

    3-2- The method of implementing the project (fattening mice using a high-fat diet) 29

    3-2-1- Preparation of aqueous and alcoholic extract of green tea 30

    3-2-2- Separating the liver and drawing blood from the mouse heart. 30

    3-3- RNA extraction 34

    3-3-1- RNA extraction tools. 34

    3-3-2- RNA extraction steps. 34 3-3-2-1- Precipitation of RNA: 35 3-3-2-2- Washing of RNA: 35 3-3-2-3- Drying of RNA sediment: 35 3-3-3 Quantitative and qualitative assessment of extracted RNA: 36 3-3-3-1- Measurement of RNA quantity: 36

    3-3-3-2- RNA quality check: 36

    3-3-3-3- RNA conservation: 37

    3-4- Gene expression check 37

    3-4-1- RT-PCR. 37

    3-4-2- cDNA replication. 39

    3-4-2-1- PCR(Polymerase Chain Reaction) 39

    3-4-2-2- Materials and tools needed to make cDNA. 43

    3-4-2-3- The method of performing cDNA production test. 44

    3-4-2-4- how to perform the RT-PCR reaction to ensure the accuracy of cDNA synthesis. 45

    3-4-2-5- Detection of PCR products by electrophoresis 47

    3-4-2-6- Devices required for electrophoresis 47

    3-4-2-7- Necessary materials for electrophoresis 47

    3-4-2-8- How to perform electrophoresis 48

    3-4-2-9- Gel detection. 48

    3-5- Real-time PCR 49

    3-5-1- Use cases of Real-time PCR. 49

    3-5-2- Different phases of a real time PCR reaction. 50

    3-5-3- Real-time PCR assay methods. 51

    3-5-3-1- non-specific assay method with Real-time PCR. 51

    3-5-4- Threshold concept and Ct. 52

    3-5-5- How to draw Melt Curve Analysis 53

    3-5-6- How to do Real time PCR. 55

    3-5-6-1- Necessary materials to perform Real time PCR. 55

    3-5-6-2-method of performing Real time PCR test. 55

    3-5-6-3- Statistical analysis 57

    3-6-Measurement of ?-Amylase in serum55

    3-5-6-3- Statistical analysis 57

    3-6-Measurement of ?-Amylase in mouse serum: 57

    3-6-1-Separation of serum from mouse blood. 57

    3-6-2- Measurement of ?-Amylase in serum by photometric method. 57

    Chapter 4 Results. 60

    4-1- Weight gain observations of test group mice 61

    4-2- Determining the quality and concentration of extracted RNA 66

    4-3- Checking the quality of cDNA synthesized by PCR 67

    4-4-Melt Curve Analysis 68

    4-4-1- Comparison of liver alpha amylase gene expression in mice Fat and normal. 70

    4-4-2-The effect of green tea on liver alpha amylase gene expression in obese mice. 71

    4-5- Measurement of alpha-amylase in serum by photometric method 72

    Chapter five: Discussion and conclusion 73

    5-1- Discussion and conclusion 74

    5-2- Suggestions 81

    Resources 83

    English summary 92

     

    Source:

     

     

     

    Abe,A., Yoshida,H., Tonozuka,T., Sakano,Y., Kamitori,S.,2005, Complexes of Thermoactinomyces vulgaris R-47 alpha-amylase 1 and pullulan model oligosaccharides provide new insight into the mechanism for recognizing substrates with alpha-(1,6) glycosidic linkages, FEBS J, Vol.272, No.23, p.6145-6153.

    Aghajari, N., [etal]., 1998, Crystal structures of the psychrophilic alpha-amylase from Alteromonas haloplanctis in its native form and complexed with an inhibitor, Protein Sci, Vol.7, No.3, p. 564–572.

    Aguiar,L.G.K.,Villela,N.R.,Bouskela,E.A.,2007, Microcirculaç?o no Diabetes: Implicaç?es nas Complicaç?es Crônicas e Tratamento da Doença,Arq Bras Endocrinol Metab ,Vol. 51, p.204-211.

    Ammann, R.W., Berk, J.E., Fridhandler, L., Ueda, M., Wegmann, W., 1973, Hyperamylasemia with carcinoma of the lung, Ann Intern Med, Vol.78, p.521-526.

    Bernfeld, P., 1955, Methods in Enzymology, Cell-wide Metabolic Alterations Associated with Malignancy, Vol.1, p.149-158.

    Booth, T., [etal]., 1948, Theory of Electrokinetic Effects, Nature, Vol. 161, No. 4081, p.83-86.

    Bose, M., [etal]., 2008, The major green tea polyphenol, (?)-epigallocatechin-3-gallate, inhibits obesity, metabolic syndrome, and fatty liver disease in high fat-fed mice, J Nutr, Vol. 138, p.1677–1683.

    Brayer, G.D., Luo, Y., Withers, S.G., 1995, The structure of human pancreatic a-amylase at 1.8 A resolution and comparisons with related enzymes, Protein Sci, Vol.4, p.1730-1742.

    Burtis, C.A., ash wood, E.R., 1999, amylase enzymes, 3rd ed. Philadelphia: W.B Saunders company, p.616-19.

    Cabrera, C., Artacho, R., Giménez, R., 2006, Beneficial Effects of Green Tea-A Review, J Am Coll Nutr, Vol. 25, No.2, p.79–99.

    Célio, L., [etal]., 2010, Oleanolic acid, a natural triterpenoid improves blood glucose tolerance in normal mice and ameliorates visceral obesity in mice fed a high-fat diet, Chemico-Biological Interactions, Vol. 185, p. 59-66.

    Cheng, A.Y., Fantus, I.G., 2005, Oral antihyperglycemic therapy for type 2 diabetes mellitus, Can. Med. Assoc. J, Vol. 172, p.213-226.

    Cramer, S., Bruns, D.E., 1979, Amylase-producing ovarian neoplasm with pseudo-Meigs' syndrome and elevated pleural fluid amylase, Cancer, Vol.44, p.1715-1721.

    Danilewsky, A., [etal]., 1862, On the specifically-acting principles of the natural and artificial pancreatic juice, Virchows Archiv für pathologische Anatomie und Physiologie, und für klinische Medizin, Vol. 25, P. 279-307.

    Davison, W.C., 1925, A Viscosimetric Method for the Quantitative Determination of Amylase, Bulletin of Johns Hopkins Hospital, Vol. 37, p.281-282.

    Elman, R., McCaughan, J.M., 1927, The Quantitative Determination of Blood Amylase with the Viscosimeter, Archive of Internal Medicine, Vol.40, p.58-64.

    Fried, M., Abramson, S., Meyer, J.H., 1987, Passage of salivary amylase through the stomach in humans, Digestive Diseases and Sciences, Vol.32, p.1097-1103.

    Frost, S.J., 1978, A simple quantitative index of the P3 amylase isoenzyme in the diagnosis of acute pancreatitis, Clin Chim Acta, vol.87, p. 23-8.

    Fuwa, H., [etal].

Investigating the expression level of liver alpha-amylase gene by Real time PCR method in the liver tissue of normal and obese mice