“House dust-mites: effect on antioxidant enzyme activities.”
Karabulut AB, Atambay M, Karaman U, Kilic E, Yazar S, Saraymen R, Dadal, N.
Med Sci Monit. 2006 Sep;12(9):CR378-81.
Why?
Wanted a broad topic that encompassed many aspects of biology…
Shadowed an immunologist
What usually causes Allergic Asthma?
Allergies!
Hygiene Hypothesis
Oxidative Stress
Allergic Asthma Background
An allergy is an IgE-mediated response to attack “invaders” like dust mite matter or cockroach matter upon inhalation or touch. Dust mite allergy is the most common form of allergic asthma. Very little genetic component, except in food cases.
American Academy of Allergy, Asthma and Immunology— http://www.aaaai.org/
Symptoms of Allergic Asthma
Wheezing, SOB, inflammation of airways upon trigger.
What is IgE allergy?
IgE is only found in mammals and is a type of antibody.
Its role might be to kill cancer cells or prevent against parasitic infection.
Karagiannis S et al (2003). “Activity of human monocytes in IgE antibody-dependent surveillance and killing of ovarian tumor cells”. Eur J Immunol 33 (4): 1030-40.
Hygiene Hypothesis Background
Our IgE has nothing to do without parasites and only kills cancer cells so it gets apathetic.
First world countries have gravitated towards sanitary systems where there is little risk for parasitic infection.
Oxidative Stress… a sword with two edges.
All life has redox potential, since oxidation rxns can prevent pathogens and increase cell signaling efficiency.
Oxidation reactions can prevent apoptosis, which is occasionally necessary, and free oxygen species can cause major illness and necrosis.
Lee Y, Shacter E (1999). “Oxidative stress inhibits apoptosis in human lymphoma cells”. J Biol Chem 274 (28): 19792-8.
Schafer F, Buettner G (2001). “Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple”. Free Radic Biol Med 30 (11): 1191-212
Dust Mite Background
Continued…
A typical house dust mite measures 420 micrometers in length and 250 to 320 µm in width
DerP1, a protease found in mite droppings.
Human skin
Cont…
Virtually unkillable, need a low relative humidity and an elevation of 9,000 feet plus.
Temperatures lower than 32 degrees are fatal, but the DerP1 and eggs remain.
Some antioxidants
Catalase (CAT)
Superoxide Dismutase (SOD)
Glutathione Peroxidase (GPx)
Higher in liver than other tissues
These three enzymes are related
Cont….
SOD converts oxygen to hydrogen peroxide, which is converted to water by the help of GPx and CAT. This process was presumably designed as a whole to inhibit initiation and promotion/transformation stage in carcinogenesis.
Oxidative Stress
Metabolic products of all human cells that need to be scavenged by antioxidants. Have some useful effects, but oxidative stress causes too much oxidation of lipids, proteins and nucleic acids.
Bowler RP, Crapo JD: Oxidative stress in allergic respiratory diseases. J
Allergy Clin Immunol, 2002; 110: 349-56
What is glutathione?
Glutathione Peroxidase Background
Your master antioxidant enzyme, neutralizes toxic materials.
Prevents inflammatory reaction of allergen
Glutathione in liver + oxidative stress = glutathione peroxidase
Superoxide Dismutase
SO/SOD
Superoxide is a negatively charged 02
Released to kill bacteria
SOD cleans up after this molecule since it is mutagenic.
SOD highest turnover number known
Catalase
Catalase
The enzyme catalase is frequently used by cells to rapidly catalyze the decomposition of hydrogen peroxide into less reactive oxygen and liquid water molecules.
Legwork
Dust was taken using a vacuum cleaner from cloth-based surfaces.
200 mg of dust were placed in lactic acid for identification under a stereo-microscope.
How was antioxidant activity measured?
SOD
NBT and another chemical generates superoxide
Every reduction of 50% in superoxide gave the units of superoxide dismutase
Cont…
CAT
The amount of enzyme which liberates half of oxygen and water from hydrogen peroxide. Every reduction of 50% is one unit.
Cont… glutathione
Paglia and Valentina- “Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase.”
J Lab Clinical Medicine 1967: 70:158-69
Protein assay
Lowry
Drabkin
Lowry et al. “Protein measurement with the Folin phenol reagent.” J Biol Chem. 1951 Nov;193(1):265-75.
Patients
In study group, those who were allergic to anything were included.
DPAP- 30 patients
DNAP- 30 patients
In control group, non-smoking, non-allergic patients with no dust mites found in their houses.
Why is CAT not a valid antioxidant against dust mites?
It is possible that CAT has a much lower affinity and binds poorly to the specific oxidation that dust mites procure. This is the hypothesis of the author.
GPx and SOD Results Discussion
GPx and SOD are only reduced in dust mite allergy, not in pollen, fungus etc. The reason for this is unknown, probably due to the protease DerP1 being more biologically reactive than pollen mediators.
Oxidation, Inflammation, and Asthma
Oxidative stress causes generalized inflammation
Mechanism of action is unknown as of 2005
A vital process of respiration is particularly vulnerable to inflammation of the bronchioles, which essentially causes asthma.
Solutions
Limit exposure
Hyposensitization
Medication
Conclusion
Prevention of dust mite allergic asthma will increase serum-bound antioxidants such as SOD and GPx and give the patient a better chance at being generally healthy. More research should be done on the mechanism of action in inflammatory asthma.
References
“Allergic Asthma.” American Academy of Allergy, Asthma and Immunology. 1 Apr.
2007 .
Bowler RP, Crapo JD: Oxidative stress in allergic respiratory diseases. J
Allergy Clin Immunol, 2002; 110: 349-56
Karagiannis S et al (2003). “Activity of human monocytes in IgE antibody-dependent
surveillance and killing of ovarian tumor cells”. Eur J Immunol 33 (4): 1030-40.
Lee Y, Shacter E (1999). “Oxidative stress inhibits apoptosis in human lymphoma cells”.
J Biol Chem 274 (28): 19792-8.
Lowry et al. “Protein measurement with the Folin phenol reagent.” J Biol Chem. 1951 Nov;193(1):265-75.
Paglia and Valentina. “Studies on the quantitative and qualitative characterization of
erythrocyte glutathione peroxidase.” J Lab Clinical Medicine 1967: 70:158-69.
Schafer F, Buettner G (2001). “Redox environment of the cell as viewed through the
redox state of the glutathione disulfide/glutathione couple”. Free Radic Biol Med
30 (11): 1191-212