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Essay: Sickle cell disease

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  • Subject area(s): Health essays
  • Reading time: 3 minutes
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  • Published: 19 September 2015*
  • File format: Text
  • Words: 610 (approx)
  • Number of pages: 3 (approx)

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Sickle cell disease is an inherited blood disease which arises because of defect in beta-globin gene, a protein component of hemoglobin. Gamma-globin genes encode the fetal globin chain which can substitute the mutated or defective beta-globin chain, but expression of gamma-globin gene is inactivated prior to birth (1). Reactivation of normal fetal globin genes and fetal hemoglobin expression (HbF) is an important therapeutic option. In this study, we used the human leukemia KU812 cells that express the fetal ??-globin genes and adult ??-globin genes. Lab scale analysis to study the effect of different concentrations of ??-Aminolevulinic acid (ALA) and sodium butyrate (NaB) on gamma-globin genes and their potential as efficient inducer of HbF for effective therapy were performed using tools like RT-qPCR, ELISA and FACS. Here we report the results of our experiment on ALA and NaB treated samples. Results indicate that ALA and NaB both induce HbF production in cells in different way. Also cell viability was affected by ALA and NaB as more dead cells were observed at high concentrations. Hence ALA and NaB is an effective therapeutic agent for sickle cell disease patients and can be studied further to evaluate its potency.
Sickle cell disease (SCD) results from substitution of an amino acid of valine for glutamic acid at position 6 of the adult ??-Globin chain which is found on human chromosome 11(2,3). Polymerization of hemoglobin occurs due to deoxygenation leading to deformed dense red blood cells and they change from regular biconcave disc shape to irregular sickled shape. This causes sickled RBC to adhere to the walls of blood vessels and lose the flexible nature to pass through blood capillaries preventing normal blood flow and decreasing delivery of oxygen to various organs and tissues causing acute chest pain. Hemoglobin is present at center of each RBC. It is made of two proteins ??-globulin and ??-globulin. HbA (??2??2) is present in most adults. In fetal life the predominant form of hemoglobin expressed is fetal hemoglobin HbF (??2??2). HbF is replaced by HbA during the post-natal period. Individuals with SCD have variant of ??-Globin gene called sickle hemoglobin (HbS). They either have two copies of variant HbSS, the primary hemoglobin present in RBC is sickle hemoglobin. Some individuals may possess one copy of HbS variant plus one copy of another ??-Globin gene variant such as HbC or Hb??-thalessamia (4). The carrier state for sickle cell disease is referred as sickle cell trait.
Fetal hemoglobin HbF ameliorates the severity of sickle cell disease, so efforts have been focused on the pharmacological induction of HbF in patients with hemoglobin disorders. Fetal hemoglobin interferes with the intracellular polymerization of sickle hemoglobin and is beneficial for patients with sickle cell disease. Sodium butyrate (NaB) induces fetal hemoglobin production by stimulating the promoter of fetal of fetal globin genes (5). Butyrate mediated induction of ??-globin chains and m-RNA is associated with increase in level of acetylation of histones H3 and H4 and decrease in level of DNA methylation at promoters of ??-globin genes. In previous study, butyrate was also shown to increase HbF by increasing the efficiency of translation of ??-globin mRNA (6). ??- Aminolevulinic acid (ALA) is the first compound in the porphyrin synthesis pathway which produces heme in mammals. The purpose of the study is to check whether ALA induces ??-globin gene expression in erythroid cells and also confirm whether sodium butyrate is a good inducer of HbF according to previous studies. The ??-globin gene expression was tested by RNA extraction and by performing RT-qPCR. Fetal hemoglobin level was tested by protein extraction and detection by ELISA and also the cell viability was tested by FACS analysis to check whether ALA or NaB is toxic to cells.

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