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Essay / Hypoxia Essay - 1191
There are different facets of hypoxia in the human body. A hypoxic situation can be localized to one region or generalized to affect the entire body. Additionally, it can be pathological or simply an adaptive mechanism that the body uses to return to homeostasis. Travel to higher altitudes, strenuous exercise, deep sea diving are all examples of normal, non-pathological, generalized hypoxic conditions. A well-known pathological and deleterious example of localized hypoxia is the growth of a cancerous tumor. Tumor hypoxia occurs due to the rapid growth and proliferation of cancer cells; blood supply and therefore oxygen levels cannot keep up with growth. Which seems to confer a beneficial protection mechanism to the infected individual; if the cancer lacked oxygen, it should stop growing, right? Fake. As amazing as the human body is at maintaining homeostasis without any input or effort from the human at the conscious level, this functionality not only keeps humans alive, but also allows damaging processes to take place. produce silently in the body. Cancer cells have the ability to alter their metabolism in these hypoxic situations, allowing other vulnerable cells to remain viable. One way tumor cells adapt is by upregulating transcription factors such as hypoxia-inducible factors (HIFs), for example. HIF-2α is a heterodimeric transcription factor with a beta subunit identified as a nuclear translocator of the aryl hydrocarbon receptor (ARNT). ). Under normal conditions, HIF-2α subunits are hydroxylated in an iron-dependent manner, at two key prolyl residues by specific prolyl hydroxylazes. HIF-2α are then recognized by the Hippel-Linadau (VH) protein...... middle of article......this is the high tumorogenicity in the cascade. Although in theory this appears to be a good idea, in research this has been shown to lack specificity and decrease the expression of HIF-1α and HIF-2α, even though HIF-1α does not have an IRE binding domain. Building on the findings of John McMillian from the seminar series, the discovery of the hydrophobic hole in the core of the HIF-2α protein, may promote additional efforts to target and block HIF-2α by binding this core, which would be more specific. to HIF-2α versus HIF-1α Additionally, agents can be designed to not only bind and inhibit conformational changes of this protein, but also play a role in the negative regulation of the VHL pathway. high prevalence of mutations in this pathway This would confer both efficacy and specificity in targeting HIF-2α and provide a better prognosis. clinically for patients with RCC.