title: Mitochondrial inactivation by Anopheles albimanus cecropin 3: molecular mechanisms.
abstract: Cecropin 3 (Ccrp3) is an antimicrobial peptide from Anopheles albimanus, which is expressed during Plasmodium berghei infection. Here, we report that synthetic Ccrp3, aside from antibacterial activity, also shows cardio regulatory functions. In rats, Ccrp3 significantly diminishes blood pressure as well as the heartbeat frequency at nanomolar concentration. Ccrp3 affect the rat cardiac muscle mitochondria, inducing uncoupling of oxidative phosphorylation, oxygen consumption and transport of Ca(2). Ccrp3 treatment of the mitochondria causes mitochondrial damage promoting oxidative stress, causing overproduction of reactive oxygen species (ROS) and inhibition of superoxide dismutase. At nM concentration, Ccrp3 inhibits superoxide dismutase activity through direct interaction, diminishing by its enzymatic activity. Ccrp3 induces the release of the pro-apoptotic marker Bax from the mitochondria. Altogether, these results suggest that Ccrp3 pro-oxidative activity on cardiac muscle mitochondria could be responsible for triggering the heartbeat frequency and blood pressure lowering observed the Ccrp3 injected rats.
authors.affiliation: Departamento de Farmacología. Dirección de investigación, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, CP 14080 Tlalpan, DF, Mexico.
authors.forename: Natalia
authors.initials: N
authors.lastname: Pavón
authors.affiliation: Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, CP 14080 Tlalpan, DF, Mexico.
authors.forename: Mabel
authors.initials: M
authors.lastname: Buelna-Chontal
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No.1, Col. Sección XVI, CP 14080 Tlalpan, DF, Mexico.
authors.forename: Luz
authors.initials: L
authors.lastname: Hernández-Esquivel
authors.affiliation: Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, CP 14080 Tlalpan, DF, Mexico.
authors.forename: Sauri
authors.initials: S
authors.lastname: Hernández
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No.1, Col. Sección XVI, CP 14080 Tlalpan, DF, Mexico.
authors.forename: Edmundo
authors.initials: E
authors.lastname: Chávez
authors.affiliation: Centro de Investigaciones sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Av. Universidad 655, CP 62501 Cuernavaca, Morelos, Mexico.
authors.forename: Renaud
authors.initials: R
authors.lastname: Condé
authors.affiliation: Centro de Investigaciones sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Av. Universidad 655, CP 62501 Cuernavaca, Morelos, Mexico. Electronic address: humberto@insp.mx.
authors.forename: Humberto
authors.initials: H
authors.lastname: Lanz-Mendoza
mesh_terms: D000818:Animals; D000852:Anopheles; D001692:Biological Transport / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D054807:Cecropins / Q000494:pharmacology*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D054807:Cecropins; D017392:Thiobarbituric Acid Reactive Substances; D002118:Calcium
keywords: Anopheles albimanus; Blood pressure; Cardiomyocyte; Cecropin 3; Mitochondria; Oxidative stress