Cellular stress associated with the differentiation of Plasmodium berghei ookinetes.
For malaria transmission, Plasmodium parasites must develop in the mosquito vector. Oxidative stress in the insect midgut, triggered by environmental changes (e.g., pH and temperature), influences the cellular signaling involved in differentiation from gametocytes to mobile ookinetes for the purpose of parasite survival. Oxidative stress activates the homeostatic response to stress characterized by the phosphorylation eIF2α, the attenuation of protein synthesis, and the transcription of genes participating in the unfolded protein response and antioxidant processes, forming a part of an integrated stress response (ISR). We hypothesized that ISR operates during the differentiation of gametocytes to ookinetes to assure Plasmodium survival. Using in-vitro conditions resembling the mosquito midgut conditions, we cultured Plasmodium berghei gametocytes to ookinetes and evaluated the redox balance by detecting reactive oxygen species and superoxide dismutase activity. Additionally, we evaluated the phosphorylation of eIF2α, the attenuation of the global protein synthesis, and the gene expression of cellular stress markers (e.g., endoplasmic reticulum chaperones and antioxidant molecules, measured by reverse-transcription quantitative polymerase chain reaction), finding that these processes were all taking place, probably to improve survival during the differentiation of Plasmodium berghei ookinetes.
a Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Avenida Universidad 655, C.P. 62100, Cuernavaca, Morelos, México.
Josefina
J
Duran-Bedolla
a Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Avenida Universidad 655, C.P. 62100, Cuernavaca, Morelos, México.
Juan
J
Téllez-Sosa
a Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Avenida Universidad 655, C.P. 62100, Cuernavaca, Morelos, México.
Humberto
H
Valdovinos-Torres
b Departamento de Farmacología and Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología, Ignacio Chávez, Juan Badiano # 1, Col. Sección XVI, C.P. 014080, Tlalpan, D.F., México.
Natalia
N
Pavón
b Departamento de Farmacología and Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología, Ignacio Chávez, Juan Badiano # 1, Col. Sección XVI, C.P. 014080, Tlalpan, D.F., México.
Mabel
M
Buelna-Chontal
a Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Avenida Universidad 655, C.P. 62100, Cuernavaca, Morelos, México.
Angel T
AT
Tello-López
a Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Avenida Universidad 655, C.P. 62100, Cuernavaca, Morelos, México.
Rocio
R
Argotte-Ramos
a Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Avenida Universidad 655, C.P. 62100, Cuernavaca, Morelos, México.
Mario Henry
MH
Rodríguez
a Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Avenida Universidad 655, C.P. 62100, Cuernavaca, Morelos, México.
María Carmen
MC
Rodríguez
D000818:Animals; D002454:Cell Differentiation; D000091342:Endoplasmic Reticulum Chaperone BiP; D004912:Erythrocytes / Q000469:parasitology*; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006790:Host-Parasite Interactions; D008018:Life Cycle Stages / Q000235:genetics*; D008288:Malaria / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D010962:Plasmodium berghei / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D061251:Primary Cell Culture; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D056811:Unfolded Protein Response
D000091342:Endoplasmic Reticulum Chaperone BiP; D015852:Eukaryotic Initiation Factor-2; D006360:Heat-Shock Proteins; D015800:Protozoan Proteins; D017382:Reactive Oxygen Species; D054464:Peroxiredoxins; D013482:Superoxide Dismutase; D019704:Protein Disulfide-Isomerases
Plasmodium differentiation; cellular stress; différenciation de Plasmodium; stress cellulaire; eIF2α; integrated stress response; réponse intégrée au stress