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A-kinase anchoring proteins coordinate inflammatory responses to cigarette smoke in airway smooth muscleW.J. Poppingal, I.H. Heijink, L.J. Holtzer, P. Skroblin, E. Klussmann, A.J. Halayko4, W. Timens, H. Maarsingh, and M. Schmidt1Published: January 30,2015 | doi: 10.1152/ajplung.00301.2014

Hey everyone, I am Rajat Goyal and I am presenting the Paper A-kinase anchoring proteins coordinate inflammatory responses to cigarette smoke in airway smooth muscle which was published on January 30, 2015 in the American Journal of Physiology Lung Cellular and Molecular Physiology1Introduction - COPDChronic Obstructive Pulmonary Disease (COPD) What causes COPD?Smokers/Allergies/Pollution/SmogSymptomsChronic coughMucus expulsion with coughFrequent respiratory infections (acute flares)Shortness of breath- exercise/fatigueLoss of weightNot enough O2 in bloodCategory of Two diseases 1. Emphysema alveolar membrane breaks down2. Chronic Bronchitis to much mucus, inflammation of lungs

2Symptoms are typically experienced at late stages of the disease

Chronic Obstructive Pulmonary Disease, abbreviated COPD, is a lung disease that makes it hard for somebody to breathe . It is due to lung damage which typically occurs due to many years of smoking, but also can occur due to pollutants, smog, and second hand smoke.

The symptoms of COPD are a chronic cough with mucous expulsion , frequent respiratory infections, and shortness of breath. Since it takes more energy to breathe, COPD patients often loose weight.

We are constantly trying to get rid of mucus via couchingsmooth muscle in lungsObstruction of bronchiole, bacteria build up, infection, pneumonia

COPD is the categorization of two diseases. In emphysema, alveolar membrane breaks down, which results in reduced gas exchange with blood due to lower surface area. Due to a break down in alveolar folds, air also has a tougher time escaping the alveoli isnt pushed out as easily to replenish with new oxygen because of damaged alveoli as wellold air is trapped, no new O2 is replenished.

2Background2-agonists inhibitors: bronchodilator (dilate airway of the lung)Stimulate cAMP3

Beta-2-agonist inhibitors are ligands which bind to beta-2-adrenoreceptor to illicit a response. In airway smooth muscle (ASM) cells, these inhibitors induces bronchodilation and relaxation of the airways, both of which are critical in relieving some of the symptoms of COPD. On the cellular level, the association of the agonist to the receptor causes an increase in cyclic AMP, an effector molecule involved in many molecular processes via signal transduction. ASM cells also posses secretory and inflammatory functions, functions that are primarily manifested through A-kinase anchoring proteins (AKAP). These class of proteins not only regulate cAMP but also protein kinase A (PKA) which is known to associate with AKAP to form a complex and is also acted on by cAMP. In humans, AKAP5 and AKAP12 also interact with beta-2-adrenoreceptors so studying their expression in COPD patients and when using CSE may provide insight on important effector molecules and the molecular mechanism of action.3Figure 2: Expression of AKAP5/12 mRNA is altered in COPD pt and by CSE4

Figure 2A, 2B, and 2C

We measured expression of AKAP5 and AKAP12 in lung tissue to see whether there was a significant change. The control consisted of people of no known physiological conditions, otherwise healthy. Stage II and Stage IV refer to patients with COPD with various severity (the latter being very severe while the former is moderate). Each dot on the figures represents a individual that contributed to the study. Evident from the figure, there was notable significant decrease in AKAP5 mRNA levels, with p