Bovine lactoferrin inhibits Plasmodium berghei growth by binding to heme.

Plasmodium berghei / drug effects Animals Lactoferrin / pharmacology Cattle Heme / metabolism Mice Hemeproteins / metabolism Malaria / parasitology Protein Binding Erythrocytes / parasitology Iron / metabolism Antimalarials / pharmacology

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
02 Sep 2024
Historique:
received: 07 06 2024
accepted: 21 08 2024
medline: 3 9 2024
pubmed: 3 9 2024
entrez: 2 9 2024
Statut: epublish

Résumé

Bovine lactoferrin (bLF) is a 77 kDa glycoprotein that is abundant in bovine breast milk and exerts various bioactive functions, including antibacterial and antiviral functions. Few studies have explored bLF activity against parasites. We found that bLF affects hemozoin synthesis by binding to heme, inhibiting heme iron polymerization necessary for Plasmodium berghei ANKA survival in infected erythrocytes, and also binds to hemozoin, causing it to disassemble. In a challenge test, bLF administration inhibited the growth of murine malaria parasites compared to untreated group growth. To determine whether the iron content of bLF affects the inhibition of malaria growth, we tested bLFs containing different amounts of iron (apo-bLF, native-bLF, and holo-bLF), but found no significant difference in their effects. This indicated that the active sites were located within the bLFs themselves. Further studies showed that the C-lobe domain of bLF can inhibit hemozoin formation and the growth of P. berghei ANKA. Evaluation of pepsin degradation products of the C-lobe identified a 47-amino-acid section, C-1, as the smallest effective region that could inhibit hemozoin formation. This study highlights bLF's potential as a novel therapeutic agent against malaria, underscoring the importance of its non-iron-dependent bioactive sites in combating parasite growth.

Identifiants

DOI: 10.1038/s41598-024-70840-6 PMID: 39223194
pubmed: 39223194
doi: 10.1038/s41598-024-70840-6
pii: 10.1038/s41598-024-70840-6
doi:

Substances chimiques

Lactoferrin EC 3.4.21.-
Heme 42VZT0U6YR
hemozoin 39404-00-7
Hemeproteins 0
Iron E1UOL152H7
Antimalarials 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

20344

Informations de copyright

© 2024. The Author(s).

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Auteurs

Momoka Obayashi (M)

Division of Molecular Functions of Food, Department of Biochemistry and Biotechnology, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan.

Momoko Kimura (M)

Division of Molecular Functions of Food, Department of Biochemistry and Biotechnology, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan.

Asako Haraguchi (A)

Laboratory of Veterinary Parasitology, School of Veterinary Medicine, Kitasato University, 23-35-1 Higashi, Towada, Aomori, 034-8628, Japan.

Mari Gotanda (M)

Division of Molecular Functions of Food, Department of Biochemistry and Biotechnology, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan.

Taiki Kitagawa (T)

Division of Molecular Functions of Food, Department of Biochemistry and Biotechnology, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan.

Misato Matsuno (M)

Division of Molecular Functions of Food, Department of Biochemistry and Biotechnology, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan.

Kozue Sakao (K)

The United Graduate School of Agricultural Sciences, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan.

Daisuke Hamanaka (D)

The United Graduate School of Agricultural Sciences, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan.

Kodai Kusakisako (K)

Laboratory of Veterinary Parasitology, School of Veterinary Medicine, Kitasato University, 23-35-1 Higashi, Towada, Aomori, 034-8628, Japan.

Tomoshi Kameda (T)

Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, 135-0064, Japan.

Hisham R Ibrahim (HR)

Division of Molecular Functions of Food, Department of Biochemistry and Biotechnology, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan.
The United Graduate School of Agricultural Sciences, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan.

Hiromi Ikadai (H)

Laboratory of Veterinary Parasitology, School of Veterinary Medicine, Kitasato University, 23-35-1 Higashi, Towada, Aomori, 034-8628, Japan. ikadai@vmas.kitasato-u.ac.jp.

Takeshi Miyata (T)

Division of Molecular Functions of Food, Department of Biochemistry and Biotechnology, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan. miyata@agri.kagoshima-u.ac.jp.
The United Graduate School of Agricultural Sciences, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan. miyata@agri.kagoshima-u.ac.jp.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Alveolata › Apicomplexa › Haemosporida › Plasmodium › Plasmodium berghei › Bovine lactoferrin inhibits Plasmodium berghei...
questionsmedicales.fr › Eucaryotes › Animaux › Bovine lactoferrin inhibits Plasmodium berghei...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Métalloprotéines › Protéines de liaison au fer › Transferrines › Lactoferrine › Bovine lactoferrin inhibits Plasmodium berghei...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Artiodactyla › Ruminants › Bovins › Bovine lactoferrin inhibits Plasmodium berghei...
questionsmedicales.fr › Facteurs biologiques › Pigments biologiques › Porphyrines › Métalloporphyrines › Hème › Bovine lactoferrin inhibits Plasmodium berghei...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Bovine lactoferrin inhibits Plasmodium berghei...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Hémoprotéines › Bovine lactoferrin inhibits Plasmodium berghei...
questionsmedicales.fr › Infection › Maladies vectorielles › Paludisme › Bovine lactoferrin inhibits Plasmodium berghei...
questionsmedicales.fr › Métabolisme › Liaison aux protéines › Bovine lactoferrin inhibits Plasmodium berghei...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Sang › Cellules sanguines › Érythrocytes › Bovine lactoferrin inhibits Plasmodium berghei...
questionsmedicales.fr › Produits chimiques inorganiques › Métaux › Métaux lourds › Fer › Bovine lactoferrin inhibits Plasmodium berghei...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antiparasitaires › Antiprotozoaires › Antipaludiques › Bovine lactoferrin inhibits Plasmodium berghei...