Effects of Metabolism
General Research Question
I am examining how metabolism affects lung cells' ability to protect against and recover from ozone induced oxidative damage.
General Background on Metabolism
When people hear the term ‘Metabolism,’ they often think of a 'thin' person that can eat constantly but never gain weight. The science of metabolism explains how this might happen. At the cellular level metabolism is the sum of all chemical reactions involved in the storage or use of energy (Marieb, 2008). Reactive oxygen species (ROS) are byproducts of metabolism, especially cellular respiration. While cells require low levels of ROS, high concentrations of the oxidants are toxic (Poncin, 2007). This means that the concentration of ROS must be controlled so that cells stay in the 'healthy' range and prevent damage to their components. Mechanisms must exist to reduce the threat of damage to cells that are exposed (temporarily or long term) to oxidants that they produce or that are found in their environment. My research is interested in what those mechanisms are and if they could be manipulated to help protect the lungs of people with increased exposure to oxidants.
One way to increase a lung cell's exposure to oxidants is exercise. When we exercise, we not only increase the amount of air we breathe in and therefore increase our lungs' exposure to air pollutants, such as ozone, but we also increase our metabolic rate and therefore increase our generation of ROS. Learn more about ROS, check out our ROS page. To mimic these conditions using lung cells grown in culture (in petri plates) we can change ozone exposure in an ozone exposure chamber and vary metabolic rate using thyroid hormone.
Major Players in Metabolism
An individual’s basal metabolic rate is highly regulated by the thyroid gland through the secretion of thyroid hormone (TH). TH is used to refer to two similar molecules, thyroxin (T4) and triiodothyronine (T3). In the Bernd lab we have shown that lung cells grown in high T3 levels consume more glucose from the growth media-- indicating that they have a higher metabolic rate. In the body, the thyroid’s secretion of TH is in turn regulated by the body’s concentration of thyroid stimulating hormone (TSH) as part of a negative feedback loop with the hypothalamus
Thyroid
Gland
Main Role:
Regulation of the body's basal metabolic rate through the secretion of
thyroid hormones (TH).
Biological
System: Endocrine System
Location:
Bi-lobed structure (structure resembles a butterfly) located on ventricular
surface of trachea
Regulation:
The thyroid's production and secretion of TH is increased
by thyroid-stimulating hormone (TSH), a hormone produced by the anterior
pituitary. TSH in turn is regulated by thyrotropin-releasing hormone
(TRH). High concentrations of TH in the blood inhibit the secretion of
TRH and TSH, creating a negative feedback loop and thereby causing
concentration of TH in the blood to return to normal.
Hormones:
-Thyroid Hormones: Thyroxine (T4) & Triiodothyronine (T3)
-Calcitonin: decreases serum calcium concentration (Thyroid C cells)
Thyroid Hormones:
Triiodothyronine (T3)
& Thyroxine (T4)
Main Role:
To increase the body's basal metabolic rate by affecting many target cells
throughout the body (Marieb et al., 759).
Location:
Made and released from Thyroid Gland, circulates in blood
Hormone
Class: Modified amino acid (tyrosine)
Other
information: Overproduction or underproduction of TH can
affect a person's activity level as seen in the case of hyper- and
hypothyroidism. To learn more about these conditions, see
below.
Anterior
Pituitary Gland
(Adenohypophysis)
Main Role:
Helps to regulate several bodily functions such as reproduction, growth and
stress through the secretion of several hormones.
Biological
System: Endocrine System
Location:
The pituitary gland is a small, tri-lobed gland located at the base of the
brain. The two main lobes, the anterior and posterior lobes, both have their
own set of distinct functions.
Regulation:
The anterior pituitary gland's hormonal secretions is
regulated by releasing/inhibiting hormones secreted be the hypothalamus. In
the case of thyroid-stimulating hormone (TSH), the particular hormone we are
looking at here, TSH secretion by the anterior pituitary is regulated by is
regulated by thyrotropin releasing hormone (TRH) as part of a negative
feedback loop.
Hormones:
Tropic Hormones
(hormones that stimulate other endocrine glands to release hormones):
-Thyroid-stimulating hormone (TSH)
-Adrenocorticotropic hormone (ACTH)
-Luteinizing hormone (LH)
-Follicle-stimulating hormone (FSH)
-Thyroid-stimulating hormone (TSH)
Direct Hormones
-Prolactin
-Endorphin
-Growth hormone
Thyroid
Stimulating Hormone (TSH)
Main Role:
Regulation of the thyroid gland's secretion of TH.
Gland:
Pituitary Gland (Anterior)
Location:
The pituitary gland is a small, tri-lobed gland located at the base of the
brain. The two main lobes, the anterior and posterior lobes, both have their
own set of distinct functions.
Hormone
Class: Peptide
Related Disorders
Hyperthyroidism Common Causes:
Prevalence:
Types:
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Symptoms:(American Thyroid Association, 2005 A)
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Hypothyroidism Common Causes: (American Thyroid Association, 2005 C; Marieb et al., 2008)
Prevalence:
Types:
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Symptoms: Insufficient levels of thyroid hormone causes different effects depending on the age of the individual (Marieb et al., 2008). These are some of the more general symptoms (American Thyroid Association, 2005 C):
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Additional Information on Thyroid Related Disorders
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Related
Lung Disorders
Exercise-Induced Bronchoconstriction
(EIB)/ Exercise-Induced Asthma (EIA) General:
Asthma is a reversible obstructive lung disease caused by hypersensitivity
of the bronchial tubes to various stimuli, such as exercise in the case of
exercise-induced asthma (EIA) (American Lung
Association, 2010). This hypersensitivity results in chronic
inflammation of the bronchial tubes causing them to swell and therefore
narrow the airways, making it harder to breath. In addition to the
continuous underlying inflammation, asthma is characterized by acute
exacerbations, usually referred to as ‘asthma attacks’ or ‘episodes’ (American Lung Association, 2010; see figure
4). Episodes are the result of a series of events, such as swelling
of the lining, tightening of surrounding muscles, and increased secretion
of mucus, all of which result in constricted airways and difficulty
breathing (American Lung Association, 2010). Potential Triggers of Asthma: (American Lung Association, 2010)
Prevalence: (American Lung Association, 2010)
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Clip from http://www.mayoclinic.com/health/exercise-induced-asthma/DS01040/ Figure 4. Video clip of what happens during an asthma attack . |