- Poster Presentation
- Open Access
Cellular toxicity triggered by bacterial inclusion bodies
© González-Montalbán et al; licensee BioMed Central Ltd. 2006
- Published: 10 October 2006
- Inclusion Body
- Intracellular Redox Status
- Mature Fibril
- Protein Production Process
- Bacterial Inclusion Body
The cytotoxicity associated with inclusion bodies and its possible impairment to recombinant protein production processes in E. coli, have been poorly studied so far . To explore these possible toxicity mechanisms we have employed a well-described system used with other kinds of protein aggregates to evaluate deleterious effects in animal cells. Cytotoxicity in animals has been associated not only with a range of proteinaceous aggregates in several degenerative diseases but also with prefibrilar aggregates of protein unrelated to any clinical diseases since they have been reported to harm cell viability by affecting biochemical parameters such as intracellular redox status and free Ca2+ levels . In this context this work contributes to support the hypothesis that misfolded proteins cause negative cellular effects as a result of exposition of hydrophobic patches or other aggregate characteristic structures on its surface.
In the present study, we prove that bacterial inclusion bodies are clearly toxic for mammalian cells. Despite the fact that it has been previously suggested that the most highly cytotoxic aggregates are the early prefibrilar assemblies rather than mature fibrils , in our case the more structured 5 h-aged inclusion bodies show a more pronounced toxic effect compared to those formed only during 1 h. However, the β-gal thermal aggregates, which have been shown to present a fibrilar pattern, behave as expected since they have not been associated with any extent of toxicity. Overall, these results support the hypothesis that different kinds of aggregates are deleterious but encourage us to study the rules that regulate the proteinaceous aggregates' toxicity.
- Gonzalez-Montalban N, Carrio MM, Cuatrecasas S, Aris A, Villaverde A: Bacterial inclusion bodies are cytotoxic in vivo in abscence of functional chaperones DnaK or GroEL. J Biotechnol. 2005, 118: 406-412. 10.1016/j.jbiotec.2005.05.024.View ArticleGoogle Scholar
- Bucciantini M, Calloni G, Chiti F, Formigli L, Nosi D, Dobson CM, Stefani M: Prefibrillar amyloid protein aggregates share common features of cytotoxicity. J Biol Chem. 2004, 279: 31374-31382. 10.1074/jbc.M400348200.View ArticleGoogle Scholar
- Corchero JL, Viaplana E, Benito A, Villaverde A: The position of the heterologous domain can influence the solubility and proteolysis of β-galactosidase fusion proteins in E. coli . J Biotechnol. 1996, 48: 191-200. 10.1016/0168-1656(96)01508-8.View ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd.