The role of a Brugia malayi p38 MAP kinase ortholog (Bm-MPK1) in parasite anti-oxidative stress responses

Akruti Patel, Agnieszka Nawrocka Chojnowski, Katie Gaskill, William De Martini, Ronald L. Goldberg, John Siekierka

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)

Abstract

Filariasis, caused by thread-like nematode worms, affects millions of individuals throughout the tropics and is a major cause of acute and chronic morbidity. Filarial nematodes effectively evade host immunological responses and are long lived within their hosts. Recently an emphasis has been placed on enzymatic and non-enzymatic anti-oxidant systems which counteract the generation of reactive oxygen species (ROS) by macrophages and granulocytes, a first line of defense against parasites. We have characterized an anti-oxidant pathway in the filarial parasite Brugia malayi related to the evolutionarily conserved human mitogen-activated p38 protein kinase and the Caenorhabditis elegans PMK-1 protein kinase stress pathways. We have expressed a recombinant p38/PMK-1 ortholog from B. malayi (Bm-MPK1) and have successfully activated the kinase with mammalian upstream kinases. In addition, we have demonstrated inhibition of Bm-MPK1 activity using a panel of known p38 inhibitors. Using the potent and highly selective allosteric p38 inhibitor, BIRB796, we have implicated Bm-MPK1 in a pathway which offers B. malayi protection from the effects of ROS. Our results, for the first time, describe a stress-activated protein kinase pathway within the filarial parasite B. malayi which plays a role in protecting the parasite from ROS. Inhibition of this pathway may have therapeutic benefit in treating filariasis by increasing the sensitivity of filarial parasites to ROS and other reactive intermediates.

Original languageEnglish
Pages (from-to)90-97
Number of pages8
JournalMolecular and Biochemical Parasitology
Volume176
Issue number2
DOIs
StatePublished - 1 Apr 2011

Fingerprint

Brugia malayi
p38 Mitogen-Activated Protein Kinases
Parasites
Oxidative Stress
Reactive Oxygen Species
Filariasis
Oxidants
Protein Kinases
Phosphotransferases
Caenorhabditis elegans
Heat-Shock Proteins
Granulocytes
Macrophages
Morbidity

Keywords

  • Brugia malayi
  • Filarial parasites
  • P38 MAPK orthologs
  • Reactive oxygen species
  • Stress-activated protein kinases

Cite this

Patel, Akruti ; Chojnowski, Agnieszka Nawrocka ; Gaskill, Katie ; De Martini, William ; Goldberg, Ronald L. ; Siekierka, John. / The role of a Brugia malayi p38 MAP kinase ortholog (Bm-MPK1) in parasite anti-oxidative stress responses. In: Molecular and Biochemical Parasitology. 2011 ; Vol. 176, No. 2. pp. 90-97.
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The role of a Brugia malayi p38 MAP kinase ortholog (Bm-MPK1) in parasite anti-oxidative stress responses. / Patel, Akruti; Chojnowski, Agnieszka Nawrocka; Gaskill, Katie; De Martini, William; Goldberg, Ronald L.; Siekierka, John.

In: Molecular and Biochemical Parasitology, Vol. 176, No. 2, 01.04.2011, p. 90-97.

Research output: Contribution to journalArticleResearchpeer-review

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