Title

Methamphetamine induces cardiomyopathy by Sigmar1 inhibition-dependent impairment of mitochondrial dynamics and function

Authors

Chowdhury S. Abdullah, Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.
Richa Aishwarya, Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.
Shafiul Alam, Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.
Mahboob Morshed, Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.
Naznin Sultana Remex, Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.
Sadia Nitu, Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.
Gopi K. Kolluru, Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.
James Traylor, Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.
Sumitra Miriyala, Department of Cell Biology and Anatomy, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.
Manikandan Panchatcharam, Department of Cell Biology and Anatomy, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.
Brandon Hartman, Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.
Judy King, Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.
Mohammad Alfrad Bhuiyan, Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital, Cincinnati, OH, 45229, USA.
Sunitha Chandran, Department of Microbiology and Immunology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.
Matthew D. Woolard, Department of Microbiology and Immunology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.
Xiuping Yu, Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.
Nicholas E. Goeders, Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.
Paari Dominic, Department of Medicine, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.
Connie L. Arnold, Department of Medicine, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.
Karen Stokes, Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.
Christopher G. Kevil, Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.
A Wayne Orr, Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.
Md Shenuarin Bhuiyan, Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA. mbhuiy@lsuhsc.edu.

Document Type

Article

Publication Date

11-17-2020

Abstract

Methamphetamine-associated cardiomyopathy is the leading cause of death linked with illicit drug use. Here we show that Sigmar1 is a therapeutic target for methamphetamine-associated cardiomyopathy and defined the molecular mechanisms using autopsy samples of human hearts, and a mouse model of "binge and crash" methamphetamine administration. Sigmar1 expression is significantly decreased in the hearts of human methamphetamine users and those of "binge and crash" methamphetamine-treated mice. The hearts of methamphetamine users also show signs of cardiomyopathy, including cellular injury, fibrosis, and enlargement of the heart. In addition, mice expose to "binge and crash" methamphetamine develop cardiac hypertrophy, fibrotic remodeling, and mitochondrial dysfunction leading to contractile dysfunction. Methamphetamine treatment inhibits Sigmar1, resulting in inactivation of the cAMP response element-binding protein (CREB), decreased expression of mitochondrial fission 1 protein (FIS1), and ultimately alteration of mitochondrial dynamics and function. Therefore, Sigmar1 is a viable therapeutic agent for protection against methamphetamine-associated cardiomyopathy.

Publication Source (Journal or Book title)

Communications biology

First Page

682

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