Children's National Health System Posters

Acute Plasticizer Exposure Alters Mitochondrial Bioenergetics in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Document Type

Poster

Abstract Category

Cardiology/Cardiovascular Research

Keywords

Di-(2-ethylhexyl)-phthalate, plasticizer, cardiomyocytes, respiration, bioenergetics

Publication Date

Spring 2019

Abstract

Background: Di-(2-ethylhexyl)-phthalate (DEHP) is a common plasticizer used in the production of polyvinyl chloride (PVC) plastics, including various medical devices such as blood storage bags and medical tubing. DEHP is not covalently bound and can leach out of plastics and into children’s blood during high-risk procedures, such as cardiopulmonary bypass and blood transfusions. Phthalate leaching raises concern for increased exposure to patients undergoing repeated medical interventions. DEHP and its primary metabolite, mono-2-ethylhexyl-phthalate (MEHP), disrupt endocrine function, which can be linked to metabolic disturbances. Previous studies have shown that DEHP exposure changes oxygen consumption in rat cardiomyocytes. Objective: To investigate the effects of acute plasticizer exposure on bioenergetics and mitochondrial respiration in human cardiomyocytes. Methods: Human induced pluripotent stem cell-derived cardiomyocytes were acutely treated with either 10 µM MEHP, 60 µM MEHP, 26 µM DEHP, or 128 µM DEHP for one hour. Mitochondrial respiration was assessed using an extracellular flux analyzer (Seahorse Biosciences, Billerica, MA). Complexes V, III and I were inhibited by oligomycin, antimycin A, and rotenone, respectively, to isolate electron transport chain functions. FCCP was used to disrupt the mitochondrial membrane and determine maximal respiration. Basal respiration, spare respiratory capacity, non-respiratory capacity, and non-mitochondrial respiration were also determined. Results/Discussion: Acute exposure to 60 um MEHP and 0.128 mM DEHP significantly increased basal respiration by 117.6 % and 84.9%, and maximal respiration by 97.6% and 33.5%, respectively, compared with controls. These results are indicative of mitochondrial biogenesis. Additional studies are necessary to investigate chronic 48 hour treatments, the mechanisms of mitochondrial biogenesis, and the effects of acute plasticizer exposure on bioenergetics in isolated rat hearts.

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Presented at Research Days 2019.

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Acute Plasticizer Exposure Alters Mitochondrial Bioenergetics in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Background: Di-(2-ethylhexyl)-phthalate (DEHP) is a common plasticizer used in the production of polyvinyl chloride (PVC) plastics, including various medical devices such as blood storage bags and medical tubing. DEHP is not covalently bound and can leach out of plastics and into children’s blood during high-risk procedures, such as cardiopulmonary bypass and blood transfusions. Phthalate leaching raises concern for increased exposure to patients undergoing repeated medical interventions. DEHP and its primary metabolite, mono-2-ethylhexyl-phthalate (MEHP), disrupt endocrine function, which can be linked to metabolic disturbances. Previous studies have shown that DEHP exposure changes oxygen consumption in rat cardiomyocytes. Objective: To investigate the effects of acute plasticizer exposure on bioenergetics and mitochondrial respiration in human cardiomyocytes. Methods: Human induced pluripotent stem cell-derived cardiomyocytes were acutely treated with either 10 µM MEHP, 60 µM MEHP, 26 µM DEHP, or 128 µM DEHP for one hour. Mitochondrial respiration was assessed using an extracellular flux analyzer (Seahorse Biosciences, Billerica, MA). Complexes V, III and I were inhibited by oligomycin, antimycin A, and rotenone, respectively, to isolate electron transport chain functions. FCCP was used to disrupt the mitochondrial membrane and determine maximal respiration. Basal respiration, spare respiratory capacity, non-respiratory capacity, and non-mitochondrial respiration were also determined. Results/Discussion: Acute exposure to 60 um MEHP and 0.128 mM DEHP significantly increased basal respiration by 117.6 % and 84.9%, and maximal respiration by 97.6% and 33.5%, respectively, compared with controls. These results are indicative of mitochondrial biogenesis. Additional studies are necessary to investigate chronic 48 hour treatments, the mechanisms of mitochondrial biogenesis, and the effects of acute plasticizer exposure on bioenergetics in isolated rat hearts.