Download presentation
Presentation is loading. Please wait.
1
PAULINA NGUYEN HHMI RECIPIENT MENTOR: DR. GANESH CHERALA LAB: OSU-COLLEGE OF PHARMACY
2
About 1 in every 12 babies in the United States is born with low birth weight Increased risk for serious health problems such as lasting disabilities and even death. Stunted growth Higher incidence of diseases
3
Poor conditions in the womb Greater susceptibility to diseases in adult life (Barker’s Hypothesis) Low protein diet (LPD)–Rodent model for LBW Similar to human epidemiological findings LPD in rodent model can be manipulated in laboratory conditions
4
Altered tissue development leads to altered development of organs such as in kidney and liver ◦ Affect renal organic transporter functionality ◦ Affects drug transport and excretion in and out of the body LBW individuals will need different drug dosages
5
Low Birth Weight LPD Various Organs Heart, etc.
6
Drug Transport & Pharmacokinetics Pharmacokinetics (PK) Study of how drug travels through the body o Absorption o Distribution o Metabolism o Excretion Drug Metabolism and Transport Renal Excretion ADMEADME
7
Transporters OAT OCT PGP PEPT MRP Blood LUMEN BasolateralMembrane
8
5 Organic Cation Transporters found in rat models 1.OCT1 2.OCT2 3.OCT3 4.OCTN1 5.OCTN2 OCT2 OCTN1 OCTN2
9
Hypothesis Low birth weight, as a result of altered perinatal environment, leads to permanent alterations in the expression of renal OCT transporters. Specific Aims To quantify mRNA expression of r enal OCT2, OCTN1, and OCTN2 at various ages To quantify protein expression of renal OCT2 at various ages
10
Study Design Birth weights noted; litters culled Control Low Protein (LP)
11
Measure the mRNA level of OCT2, OCTN1, and OCTN2 expression in male and female offspring in both LP and Control groups using RT-PCR Measure the protein expression of OCT2 in male and female offspring in both LP and Control groups using western blotting
12
◦ Samples from both LP and control groups: Day 28 males and females Day 65 males and females Day 150 males and females β-actin ◦ Positive control Same sample used on all plates ◦ Negative Control Nuclease-free H2O
16
* * *
17
* * * * Statistically Significant
20
Tissue Tissue Homogenate
21
27 fold decrease in expression of OCT2 in Day 150 LP females relative to control (regular diet) females Effect of LP diet seen in later life
22
Sex hormone regulation of OCT2 a possible reason for 27 fold difference in LP Day 150 females Sex hormone regulation of OCT2 Testosterone up-regulates expression of OCT2 Estrogen down-regulates expression of OCT2
23
Howard Hughes Medical Institute Cripps Funding Cherala Lab ◦ Dr. Ganesh Cherala ◦ Barent DuBois ◦ Jacob Pearson ◦ Dr. Shobana Ganesan ◦ Tahir Mahmood ◦ Shawn Mahmood ◦ Alexandru Cioara OSU-College of Pharmacy Dr. Kevin Ahern
24
Cherala G, Shapiro BH, and D'mello AP (2006) Two low protein diets differentially affect food consumption and reproductive performance in pregnant and lactating rats and long-term growth in their offspring. J Nutr 136: 2827–2833 Kathleen M. Giacomini, et al. (2010) Membrane transporters in drug development Nature Reviews Drug Discovery, 215-236 Hagenbuch, B (2010) Drug Uptake Systems in Liver and Kidney: A Historic Perspective Clinical Pharmacology & Therapeutics 87 1, 39–47
Similar presentations
© 2025 SlidePlayer.com. Inc.
All rights reserved.