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The role of a Brugia malayi p38 MAP kinase ortholog (Bm-MPK1) in parasite anti-oxidative stress responses.
Mol Biochem Parasitol. 2011 Apr; 176(2):90-7.MB

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.

Authors+Show Affiliations

Department of Chemistry and Biochemistry and The Herman and Margaret Sokol Institute for Pharmaceutical Life Sciences, Montclair State University, Montclair, NJ 07043, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21185874

Citation

Patel, Akruti, et al. "The Role of a Brugia Malayi P38 MAP Kinase Ortholog (Bm-MPK1) in Parasite Anti-oxidative Stress Responses." Molecular and Biochemical Parasitology, vol. 176, no. 2, 2011, pp. 90-7.
Patel A, Chojnowski AN, Gaskill K, et al. The role of a Brugia malayi p38 MAP kinase ortholog (Bm-MPK1) in parasite anti-oxidative stress responses. Mol Biochem Parasitol. 2011;176(2):90-7.
Patel, A., Chojnowski, A. N., Gaskill, K., De Martini, W., Goldberg, R. L., & Siekierka, J. J. (2011). The role of a Brugia malayi p38 MAP kinase ortholog (Bm-MPK1) in parasite anti-oxidative stress responses. Molecular and Biochemical Parasitology, 176(2), 90-7. https://doi.org/10.1016/j.molbiopara.2010.12.008
Patel A, et al. The Role of a Brugia Malayi P38 MAP Kinase Ortholog (Bm-MPK1) in Parasite Anti-oxidative Stress Responses. Mol Biochem Parasitol. 2011;176(2):90-7. PubMed PMID: 21185874.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of a Brugia malayi p38 MAP kinase ortholog (Bm-MPK1) in parasite anti-oxidative stress responses. AU - Patel,Akruti, AU - Chojnowski,Agnieszka Nawrocka, AU - Gaskill,Katie, AU - De Martini,William, AU - Goldberg,Ronald L, AU - Siekierka,John J, Y1 - 2010/12/24/ PY - 2010/11/11/received PY - 2010/12/15/revised PY - 2010/12/20/accepted PY - 2010/12/28/entrez PY - 2010/12/28/pubmed PY - 2011/8/2/medline SP - 90 EP - 7 JF - Molecular and biochemical parasitology JO - Mol Biochem Parasitol VL - 176 IS - 2 N2 - 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. SN - 1872-9428 UR - https://www.unboundmedicine.com/medline/citation/21185874/The_role_of_a_Brugia_malayi_p38_MAP_kinase_ortholog__Bm_MPK1__in_parasite_anti_oxidative_stress_responses_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-6851(10)00324-5 DB - PRIME DP - Unbound Medicine ER -