Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of Hemozoin in Suppressing Hsp70 and NF-κB activation

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Standard

Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia : Role of Hemozoin in Suppressing Hsp70 and NF-κB activation. / Kempaiah, Prakasha; Dokladny, Karol; Karim, Zachary; Raballah, Evans; Ong'echa, John M; Moseley, Pope L; Perkins, Douglas J.

I: Molecular Medicine, Bind 22, 2016, s. 570-584.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Kempaiah, P, Dokladny, K, Karim, Z, Raballah, E, Ong'echa, JM, Moseley, PL & Perkins, DJ 2016, 'Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of Hemozoin in Suppressing Hsp70 and NF-κB activation', Molecular Medicine, bind 22, s. 570-584. https://doi.org/10.2119/molmed.2016.00130

APA

Kempaiah, P., Dokladny, K., Karim, Z., Raballah, E., Ong'echa, J. M., Moseley, P. L., & Perkins, D. J. (2016). Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of Hemozoin in Suppressing Hsp70 and NF-κB activation. Molecular Medicine, 22, 570-584. https://doi.org/10.2119/molmed.2016.00130

Vancouver

Kempaiah P, Dokladny K, Karim Z, Raballah E, Ong'echa JM, Moseley PL o.a. Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of Hemozoin in Suppressing Hsp70 and NF-κB activation. Molecular Medicine. 2016;22:570-584. https://doi.org/10.2119/molmed.2016.00130

Author

Kempaiah, Prakasha ; Dokladny, Karol ; Karim, Zachary ; Raballah, Evans ; Ong'echa, John M ; Moseley, Pope L ; Perkins, Douglas J. / Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia : Role of Hemozoin in Suppressing Hsp70 and NF-κB activation. I: Molecular Medicine. 2016 ; Bind 22. s. 570-584.

Bibtex

@article{da9ec8f307584677963e7baa04a709a4,
title = "Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of Hemozoin in Suppressing Hsp70 and NF-κB activation",
abstract = "Severe malarial anemia [SMA, hemoglobin (Hb) <5.0 g/dL] is a leading cause of global morbidity and mortality among children residing in Plasmodium falciparum transmission regions. Exploration of molecular pathways through global gene expression profiling revealed that SMA was characterized by decreased HSPA1A, a heat shock protein (Hsp) 70 coding gene. Hsp70 is a ubiquitous chaperone that regulates Nuclear Factor-kappa B (NF-κB) signaling and production of pro-inflammatory cytokines known to be important in malaria pathogenesis (e.g., IL-1β, IL-6 and TNF-α). Since the role of host Hsp70 in malaria pathogenesis is unexplored, we investigated Hsp70 and molecular pathways in children with SMA. Validation experiments revealed that leukocytic HSP70 transcripts were reduced in SMA relative to non-severe malaria, and that intraleukocytic hemozoin (PfHz) was associated with lower HSP70. HSP70 was correlated with reticulocyte production and Hb. Since glutamine (Gln) up-regulates Hsp70, modulates NF-κB activation, and attenuates over-expression of pro-inflammatory cytokines, circulating Gln was measured in children with malaria. Reduced Gln was associated with increased risk of developing SMA. Treatment of cultured peripheral blood mononuclear cells (PBMCs) with PfHz caused a time-dependent decrease in Hsp70 transcripts/protein, and NF-κB activation. Gln treatment of PBMCs overcame PfHz-induced suppression of HSP70 transcripts/protein, reduced NF-κB activation, and suppressed over-expression of IL-1β, IL-6 and TNF-α. Findings here demonstrate that SMA is characterized by reduced intraleukocytic HSP70 and circulating Gln, and that PfHz-induced suppression of HSP70 can be reversed by Gln. Thus, Gln supplementation may offer important immunotherapeutic options for futures studies in children with SMA.",
author = "Prakasha Kempaiah and Karol Dokladny and Zachary Karim and Evans Raballah and Ong'echa, {John M} and Moseley, {Pope L} and Perkins, {Douglas J}",
year = "2016",
doi = "10.2119/molmed.2016.00130",
language = "English",
volume = "22",
pages = "570--584",
journal = "Molecular Medicine",
issn = "1076-1551",
publisher = "BioMed Central",

}

RIS

TY - JOUR

T1 - Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia

T2 - Role of Hemozoin in Suppressing Hsp70 and NF-κB activation

AU - Kempaiah, Prakasha

AU - Dokladny, Karol

AU - Karim, Zachary

AU - Raballah, Evans

AU - Ong'echa, John M

AU - Moseley, Pope L

AU - Perkins, Douglas J

PY - 2016

Y1 - 2016

N2 - Severe malarial anemia [SMA, hemoglobin (Hb) <5.0 g/dL] is a leading cause of global morbidity and mortality among children residing in Plasmodium falciparum transmission regions. Exploration of molecular pathways through global gene expression profiling revealed that SMA was characterized by decreased HSPA1A, a heat shock protein (Hsp) 70 coding gene. Hsp70 is a ubiquitous chaperone that regulates Nuclear Factor-kappa B (NF-κB) signaling and production of pro-inflammatory cytokines known to be important in malaria pathogenesis (e.g., IL-1β, IL-6 and TNF-α). Since the role of host Hsp70 in malaria pathogenesis is unexplored, we investigated Hsp70 and molecular pathways in children with SMA. Validation experiments revealed that leukocytic HSP70 transcripts were reduced in SMA relative to non-severe malaria, and that intraleukocytic hemozoin (PfHz) was associated with lower HSP70. HSP70 was correlated with reticulocyte production and Hb. Since glutamine (Gln) up-regulates Hsp70, modulates NF-κB activation, and attenuates over-expression of pro-inflammatory cytokines, circulating Gln was measured in children with malaria. Reduced Gln was associated with increased risk of developing SMA. Treatment of cultured peripheral blood mononuclear cells (PBMCs) with PfHz caused a time-dependent decrease in Hsp70 transcripts/protein, and NF-κB activation. Gln treatment of PBMCs overcame PfHz-induced suppression of HSP70 transcripts/protein, reduced NF-κB activation, and suppressed over-expression of IL-1β, IL-6 and TNF-α. Findings here demonstrate that SMA is characterized by reduced intraleukocytic HSP70 and circulating Gln, and that PfHz-induced suppression of HSP70 can be reversed by Gln. Thus, Gln supplementation may offer important immunotherapeutic options for futures studies in children with SMA.

AB - Severe malarial anemia [SMA, hemoglobin (Hb) <5.0 g/dL] is a leading cause of global morbidity and mortality among children residing in Plasmodium falciparum transmission regions. Exploration of molecular pathways through global gene expression profiling revealed that SMA was characterized by decreased HSPA1A, a heat shock protein (Hsp) 70 coding gene. Hsp70 is a ubiquitous chaperone that regulates Nuclear Factor-kappa B (NF-κB) signaling and production of pro-inflammatory cytokines known to be important in malaria pathogenesis (e.g., IL-1β, IL-6 and TNF-α). Since the role of host Hsp70 in malaria pathogenesis is unexplored, we investigated Hsp70 and molecular pathways in children with SMA. Validation experiments revealed that leukocytic HSP70 transcripts were reduced in SMA relative to non-severe malaria, and that intraleukocytic hemozoin (PfHz) was associated with lower HSP70. HSP70 was correlated with reticulocyte production and Hb. Since glutamine (Gln) up-regulates Hsp70, modulates NF-κB activation, and attenuates over-expression of pro-inflammatory cytokines, circulating Gln was measured in children with malaria. Reduced Gln was associated with increased risk of developing SMA. Treatment of cultured peripheral blood mononuclear cells (PBMCs) with PfHz caused a time-dependent decrease in Hsp70 transcripts/protein, and NF-κB activation. Gln treatment of PBMCs overcame PfHz-induced suppression of HSP70 transcripts/protein, reduced NF-κB activation, and suppressed over-expression of IL-1β, IL-6 and TNF-α. Findings here demonstrate that SMA is characterized by reduced intraleukocytic HSP70 and circulating Gln, and that PfHz-induced suppression of HSP70 can be reversed by Gln. Thus, Gln supplementation may offer important immunotherapeutic options for futures studies in children with SMA.

U2 - 10.2119/molmed.2016.00130

DO - 10.2119/molmed.2016.00130

M3 - Journal article

VL - 22

SP - 570

EP - 584

JO - Molecular Medicine

JF - Molecular Medicine

SN - 1076-1551

ER -

ID: 165178687