Iron Regulatory Protein, Research Paper Example

The body of a mammal requires iron to function normally, insufficient or excess in supply of this product in the body can result in hazardous effects. To balance iron in the body as required, the body uses an Iron Regulatory protein (IRP). The protein is divided into two; IRP-1 that contains enzyme aconitase-1 that helps to convert citrate into isocitrate, and IRP-2 which is like IRP-1 but does not contain aconitase-1 protein. The research will prove the effect of balanced and unbalanced iron content in the body.

The first study aims to find out whether migraine, a neurological disorder that causes   pain in some parts the head with flu-like symptoms, is associated with genetic polymorphism of IRPs genes. Several studies have been carried out to elucidated the comorbid of migraine and genetic back ground but the data provided is so limited and not consistent (26,27). Data taken from European and Asian race women in single nucleotide polymorphism samples shows that there is a relationship between some physiological disorder and migraine. The disorders include; TNF-a rs673, CCR2 rs1799864, TGFB1 rs1800469, NOS3 rs3918226, and IL-9 rs2069885. In different studies data shows that oxidative stress is the pathogenesis of the disease, patients with migraine that applied oxidative supplements shown some improvement recover from the disease. Iron is believed to be the cause of this oxidative stress. The oxidative stress on tissues causes damage to central nervous system, though this damage is blamed to iron as oxidative agent. Iron is still very vital in the body for some other metabolic functions. Unbalanced iron in the body can be harmful. It is assumed that iron is the cause of oxidation that causes injuries to the central nervous system. Iron regulator Proteins (IRPs) are responsible to catalyse homone that reduces iron storage in the bod in case of excessive iron in the body. IRPs also stimulates hormones that increase iron absorption and storage in the body in case of iron insufficience.  Another study was curried out to ascertain whether or not the migraine headache is associated with iron imbalance. Various samples proved from migraine patients proved that the assumption was not true. It was confirmed that migraine is associated with G/G genotype of Iron regulatory proteins single nucleotide polymorphism. Age, race, gender and smoking is related to migraine pathogenesis though this study is has inconsistence data and do not meet HWE standards. Some other reliable studies shows that environment is also related to migraine prevalence. I recommend that some more studies to be carried in different countries to ascertain more factors that may contribute to migraine. Its there concluded that migraine is associated with genetic polymorphisms.

The second study is on whether IRPs genetic modification is associated with Age-related macular degradation (AMD). AMD is a disease characterized by visual impairment. Iron is hypothesized as one of the causes of AMD as it through oxidative stress which damages the retina. In study patients who used antioxidants showed improvement and recovery from the disease while patients who succumbed to AMD found to have accumulation of iron in retinal nerves but iron accumulation is a hereditary disease caused by gene mutation. Iron is an oxidative agent that cause harm on retinal nerves. A balanced iron homeostasis is largely involved in the post-transcriptional level through the IRP1 by protein enzyme and IRP2 UTR of mRNAs protein to control (Thomson 1999). Our study also proves that age, gender, sex, race, and smoking is highly associated with AMD. Our study also showed that cigarette smoking is not associated with AMD but the study did not include passive smokers. In different clinical study elucidates that passive smokers who stayed with active smokers for more than five years were positive for AMD. Age on the other hand is highly affected in that AMD most affect are old people. In terms of race the Asian and European people are the most vulnerable to AMD. Single nucleotide polymorphism inflammation and oxidative stress are caused are convincingly confirmed evidence of ADM pathogenesis. Other contributing factors to AMD pathogenesis are environment and ultraviolet rays.

Our third study aims at finding out whether iron regulatory proteins are associated with the functioning of the pulmonary and cardiovascular systems. IRPs are involved in metabolism by containing by binding mRNAs to IREs preventing translation of mRNAs. In this way, IRPs increase the absorption of iron-reducing storage and transportation of irons thus maintaining balanced intercellular iron exchange (Leedman 1999). Studies show that IRP-1 helps in coordinating the stability between erythropoiesis and iron in the body. Mice that were given an iron-deficient diet experienced sudden death meaning that iron is important in pulmonary and cardiovascular system.

Our fourth study is whether iron regulatory proteins are associated with control of metabolism of iron in mammals. Mammalian iron is regulated by sensory and regulated networks by metabolizing iron at transcriptional and posttranscriptional levels. IRP1 and IRP2 coordinates’ post-transcriptional control using mRNA in absorption and retention in cell (Eisenstein 2014). There are multiple ways in which IRP system responds to same effectors, as like the manner with which IRPs modify function of a given messenger RNA. This study shows that IRPs helps in balancing irons in the body.

The fifth study will be whether running and intensive workouts induces chemical changes and behavior of genes involved in the iron metabolism. In the experiment ferritin had negligible changes after the race but there was notable change in iron content within three hours after the race. The iron remained the same after just before the race and 24 hours after the race. This implies that a lot of iron was involved in oxygen transportation by hemoglobin throughout the body. During intense activities more oxygen is needed to be transported throughout the body as fast as possible to help rapid respiration by hemoglobin. We measure the mRNA level of the gene in the leukocyte of an athlete in a normal state, before running and after running. Measure the morphology of serum concentration of ferritin, Co-creative protein, and iron content in the blood. The results show there was no variation in the level of serum iron, ferritin but the mRNA and protein level changes occurred. The study shows that mRNA gene metabolism was independent of iron serum. An mRNA gene decreased 3 hours after the marathon but returned to the normal level after 24 hours. During exercise, changes in many plasma parameters influence intracellular homeostasis (Rouault 2015). It was also observed that oxidative stress was also the cause of the decline mRNA gene.

Our next study is on how local inflammation can be controlled by IRPs. Iron balance is regulated by hormones from the liver that when the iron is on a high level, the hormone hepcidin is secreted to stop farther absorption or recycling. To confirm our study acute mice were subjected to IRP deficiency and results were that they experienced local inflammation. Turpentine was introduced to increase protein in the liver and treat the mice. The mice showed some improvement. Turpentine introduces hepcidin hormone in the liver to balance iron serum. IRP-1 and IRP-2 animals had some capabilities to overcome local inflammation evidenced in reduced serum iron (Eisenstein 2000). It, therefore, implies that IRPs are associated with local inflammation.

Our last study is find out whether iron regulation proteins is associated with Iron Deficiency Anemia. Very little is known on the association between IFP mutation and IDA. However, our study shows that the GG genotype of IRP-1 was affected by IDA while AG locus was resistant. Those with mRNA have no increase in post-IDA PCBP1 and PCBP2 mRNA expression levels. IRP-2 recorded variant results in IDA control. Polymorphisms in the IRP1 and IRP2 gene may be linked to IDA; this means that in times of iron deficiency, IRPs stimulates absorption of iron to until it reaches the required level (Goforth 2010). Study shows that people with rs867469 GG genotype are vulnerable to IDA and have low iron level and weak in the body. After treatment, it was observed that there was reduction in ferritin, Hb, and TS but Hscrp increased in GG genotype, which roves the possibility of GG genotype having lower iron content and high inflammation characteristics. This study helps in identifying genetic risk factors of IDA and find appropriate treatment.

Based on the above discussion, it is therefore concluded IRPs are used to regulate and balance iron content in the body. It plays an important role in mammary lives without which will lead to acute diseases that may result to death of mammals.

References

Viatte, L., Gröne, H. J., Hentze, M. W., & Galy, B. (2009). In vivo role (s) of the iron regulatory proteins (IRP) 1 and 2 in aseptic local inflammation. Journal of molecular medicine, 87(9), 913-921.

Grzybkowska, A., Anczykowska, K., Ratkowski, W., Aschenbrenner, P., Antosiewicz, J., Bonis?awska, I., & ?ychowska, M. (2019). Changes in Serum Iron and Leukocyte mRNA Levels of Genes Involved in Iron Metabolism in Amateur Marathon Runners—Effect of the Running Pace. Genes, 10(6), 460.

Eisenstein, R. S. (2000). Iron regulatory proteins and the molecular control of mammalian iron metabolism. Annual review of nutrition, 20(1), 627-662.

Zhang, D. L., Ghosh, M. C., & Rouault, T. A. (2014). The physiological functions of iron regulatory proteins in iron homeostasis-an update. Frontiers in pharmacology, 5, 124.

Synowiec, E., Pogorzelska, M., Blasiak, J., Szaflik, J., & Szaflik, J. P. (2012). Genetic polymorphism of the iron-regulatory protein-1 and-2 genes in age-related macular degeneration. Molecular biology reports, 39(6), 7077-7087.

Ramroodi, N., Jahantigh, M., Nakhzari-Khodakheir, T., Ranjbar, N., & Sanadgol, N. (2017). Correlation between iron regulatory protein-1 (G-32373708A) and-2 (G-49520870A), gene variations and migraine susceptibility in southeast Iran: A case-control study. Egyptian journal of basic and applied sciences, 4(2), 123-128.