Lymphocyte toxicity of prion fragments.

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Lymphocyte toxicity of prion fragments. Abstract Text:

Jayaraman Murali,Rajadas Jayakumar,

Prion protein fragments that are extracted from the brains of patients with Gerstmann-Straussler-Scheinker disease are known to have stimulating action on circulating leukocytes. In particular, the amyloidogenic hydrophobic prion peptide HuPrP (113-127) AGAAAAGAVVGGLGG has been reported to be associated with significant cellular toxicity. In this paper we show that the self assembled form of HuPrP (113-127) and its valine rich domains viz. GAVVGGLG [HuPrP (119-126)] and VVGGLGG [HuPrP (121-127)] are toxic to peripheral lymphocytes. To explore the cytotoxic mechanism of these fragments, we studied 3-(4,5-dimethylthiazol-2yl)-2-5-diphenyltetrazolium bromide (MTT) reduction, reactive oxygen species (ROS) generation, calcium influx and raft sequestration of' peptide treated lymphocytes. Langmuir monolayer studies on these peptides showed a maximum lipid perturbing property of HuPrP (121-127) as compared to the other two fragments. MTT reduction assays on lymphocytes treated with peptides indicated that the prion peptide fibrils are relatively more toxic than freshly solubilized peptide preparations. Lymphocytes treated with HuPrP (121-127), HuPrP (113-127) and HuPrP (119-126) fibrils underwent 60%, 30% and 40% cell death, respectively. Abeta(1-42), HuPrP (119-126) and HuPrP (121-127) fibrils caused 4 fold increases in intracellular ROS as compared with control cells. However, HuPrP (113-127) fibrils lacked such a significant ROS generating activity, indicating that a subtle difference in sequence leads to a difference in the toxic mechanism in the cell. HuPrP (119-126) and HuPrP (121-127) fibrils also produced maximum raft sequestration and calcium influx. Taken together, these data suggest that the assemblage of prion fragments has significant toxic activity on peripheral lymphocytes, a finding with implications for controlling reactive lymphocytes in prion infected subjects.

Lymphocyte toxicity of prion fragments. Publishing Authors By Initials

J Murali,R Jayakumar,

For similar proteins: prions research abstracts see: proteins: prions research

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Lymphocyte toxicity of prion fragments. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of biochemistry

VOLUME: 139

Page Numbers: 329-38

Journal Abbreviation: J. Biochem.

ISSN: 0021-924X

DAY: 19

MONTH: Mar

YEAR: 2006

Lymphocyte toxicity of prion fragments. Information

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LANGUAGE: eng

NlmUniqueID: 376600

Lymphocyte toxicity of prion fragments. Keywords Mesh Terms:

KEYWORDS: Prions

MESH TERMS: toxicity

Chemical & Substance for Abstract: Lymphocyte toxicity of prion fragments. Information

Substance Name: Prions

Registry Number: 0

Grant and Affiliation Information for Lymphocyte toxicity of prion fragments.

AFFILIATION: Bioorganic and Neurochemistry Laboratory, Central Leather Research Institute, Adyar, Chennai-600 020, India.

Country: Japan

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MEDLINETA: J Biochem

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