Related Experiment Videos
Covalent modification of proteins by cocaine
Shi-Xian Deng1, Narine Bharat, Marian C Fischman
1Department of Medicine, Division of Clinical Pharmacology and Experimental Therapeutics, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA.
Summary
Cocaine can alter proteins in the body by forming covalent bonds with lysine residues. This protein modification in rats and humans may trigger an immune response, potentially explaining autoimmune effects of cocaine.
Area of Science:
- Biochemistry
- Immunology
- Pharmacology
Background:
- Cocaine is known to have various physiological effects.
- The precise molecular mechanisms underlying cocaine's long-term actions and autoimmune effects are not fully understood.
Purpose of the Study:
- To investigate the molecular interactions between cocaine and proteins in vivo.
- To determine if cocaine-induced protein modifications elicit an immune response.
Main Methods:
- In vitro experiments to assess cocaine's reactivity with amino acids.
- Analysis of plasma from cocaine-exposed rats and human subjects for protein modifications.
- Immunization of mice with modified proteins and detection of antibodies in human plasma.
Main Results:
- Cocaine specifically acylates lysine residues in vitro.
- Covalently modified proteins were identified in the plasma of chronically cocaine-exposed rats and humans.
- Specific antibodies against modified proteins were elicited in mice and detected in human subjects.
Conclusions:
- Cocaine's methyl ester can covalently modify proteins by targeting lysine residues.
- These protein modifications are present in vivo and are immunogenic.
- Covalent protein modification offers a potential explanation for cocaine's autoimmune effects and a novel biochemical target for understanding its long-term actions.