Stress biomarker concentrations and detection in bodily fluids

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1 NBMC BST III Workshop Arlington VA Stress biomarker concentrations and detection in bodily fluids Andrew Steckl and Prajokta Ray Nanoelectronics Laboratory, University of Cincinnati Hormones signaling molecules secreted by endocrine glands into blood stream transported by circulatory system to specific to specific organs calling for action to regulate body functions.

2 Hormone Categorization Source Glands (Endocrine System) Body Organ Affected Blood Vessel Endocrine cell Action Mechanism Hydrophilic travel freely through bloodstream, bind to receptors on outer surface of cells > triggers cell response > activate enzyme in cell which adjusts (up/down) rate of biochemical processes. Lipophilic travel through blood stream embedded in water-soluble proteins, can penetrate cell membrane, bind to receptor inside cell, hormone-receptor complex moves to nucleus & binds to DNA section > trigger cell response > activates enzyme in cell which adjusts (up/down) rate of biochemical processes Cell surface receptors Hydrophilic signal Carrier protein Target cell Intracellular receptor Hydrophobic signal 2

3 Stress Biomarkers I - Catecholamines Epinephrine (aka adrenaline) - Fight-or-flight hormone (C 9 H 13 NO Da) Secreted by adrenal glands in response to stress Hydrophilic Increases heart rate Increases blood flow skeletal muscles Increases blood glucose Alters mental functioning Norepinephrine (C 8 H 11 NO Da) Similar to epinephrine No methyl group in amine tail benzene ring Dopamine (C 8 H 11 NO Da) No hydroxyl in amine tail amine side chain hydroxyl groups catechol 3

4 Stress Biomarkers II Cortisol - glucocorticoid (C 21 H 30 O Da) Secreted by adrenal glands in response to stress & low blood sugar, regulated by the pituitary gland Lypophilic Anti-inflammatory, immunosuppressive Control blood glucose Serotonin - neurotransmitter (C 10 H 12 N 2 O Da) Produced in the digestive track, brain Amphiphilic Mood regulation, appetite Anti-depressant Neuropeptide Y- 36-amino acid peptide (C 190 H 287 N 55 O kda) Neurotransmitter in brain, sympathetic nervous system Lypophilic Controls appetite, reduces anxiety, stress Lowers blood pressure 4

5 Biomarker Molecule Type, Weight Physiological Concentration Related Health Condition Orexin A (Neuropeptide) 33 - amino acid C 152 H 243 N 47 O 44 S kda Lipophilic Plasma: µg/l Body fluids: under study Controls consciousness Sleep disorder, appetite Affects histamine, dopamine, NPE Cortisol Glucocorticoid C 21 H 30 O Da Lipophilic Blood 5-23 (am) 3-16 µg/dl (pm) Sweat: ng/ml Urine: µg/24hr Saliva: µg/l Stress hormone Acute stress, low-blood glucose concentration etc. Obesity, depression, diabetes. Dopamine Neurotransmitter C 8 H 11 NO Da Lipophilic Plasma: 21.8 ± 9.5 ng/l Urine: µg/24hr Sweat: Under study. Initiates happiness (natural, induced) NPY (Neuropeptide Y) 36 amino acid C 190 H 287 N 55 O kda Lipophilic Plasma: pg/ml Sweat: pg/ml Saliva: pmol/L Low NPY: Depression, anxiety, PTSD Food intake Stress response Cardiovascular function IL-6 (Interleukin-6) Cytokine 22kDa-28 kda Amphiphilic Plasma: pg/ml Sweat: pg/ml Saliva: 1.8 ± 4.25 pg/ml Urine : ng/l Secreted by T- cells to stimulate immune response Inflammatory and auto immune process TNF α Tumor Necrosis Trimer - 52 kda Hydrophilic Plasma: pg/ml Sweat: pg/ml Urine: ng/l Immune cell regulation Immune response Disease fighting process Oxytocin C 43 H 66 N 12 O 12 S 2-1 kda Hydrophilic Plasma: pg/ml Body fluids: Under study Most imp. medicine in current healthcare Social bonding, anxiety, maternity, child birth. CTT (Cardiac Troponin T) Protein 36 kda Hydrophobic core Plasma to µg/l Body fluids: Under study Key biomarker for heart disorder. (increased troponin in plasma) Norepinephrine Neurotransmitter C 8 H 11 NO Da Hydrophilic Blood: pg/ml Urine: µg/24 hr Other: Under study Stress hormone High glucose, increased heart rate Anxiety, high blood pressure BDNF (Brain derived neurotropic factor) Protein 14 kda 32 kda Lipophilic Serum: ng/ml Plasma: Median: 92.5 pg/ml Neuropsychiatric disorder Depression, schizophrenia Serotonin Neurotransmitter C 10 H 12 N 2 O Da Amphiphilic Blood: 101 to 283 ng/ml. Urine: µmol/24 hr Mood regulation, appetite Antidepressant. 5

6 Biomarker Molecular Weight & Concentration in Blood Conc. (µg/dl) lipophilic hydrophilic amphiphilic 6

7 Biomarker Molecular Weight & Concentration in Urine lipophilic hydrophilic amphiphilic Considering 1000 ml urine generated in 24 hr 7

8 Biomarker Molecular Weight & Concentration in Saliva lipophilic hydrophilic amphiphilic 8

9 Biomarker Molecular Weight & Concentration in Sweat lipophilic hydrophilic amphiphilic 9

10 A. J. Steckl - NBMC BST III Workshop Arlington VA Cortisol, Serotonin, NPY In Several Body Fluids Urine (?) Sweat (?) Saliva (?) 10

11 Acknowledgments Prajokta Ray, Hua Li, Shima Dalirirad UES Stephaney Shanks, Melanie Tomczak AFRL Jorge Chavez, Craig Murdock DCN Roy Chung, Shrin Kuo, Nate Roode UA Min Jia, Ray Runyon, Perry Skeath, Esther Sternberg For additional information, please send to Funding AFRL/UES, NSF 11