PMID- 29476339 OWN - NLM STAT- MEDLINE DCOM- 20180710 LR - 20181202 IS - 1432-1955 (Electronic) IS - 0932-0113 (Linking) VI - 117 IP - 4 DP - 2018 Apr TI - Role of glutathione, ROS, and Bcl-xL in the inhibition of apoptosis of monocyte-derived dendritic cells by Leishmania mexicana promastigotes. PG - 1225-1235 LID - 10.1007/s00436-018-5804-z [doi] AB - Dendritic cells (DCs) are one of the principal host cells of the obligate intracellular parasite Leishmania that can survive and reproduce within cells due to the ability to regulate different cellular events, including apoptosis. Inhibition of host cell apoptosis is a strategy employed by multiple pathogens to ensure their survival in the infected cell. We have previously reported that Leishmania mexicana promastigotes and amastigotes inhibit camptothecin-induced apoptosis of monocyte-derived dendritic cells (moDCs) through the downregulation of p38 and JNK phosphorylation. The upregulation of glutathione (GSH), the most important regulator of reactive oxygen species (ROS) concentration, has proven to protect cells from apoptosis through the inhibition of JNK1. Another mechanism employed by cells for the protection of apoptosis is the expression of anti-apoptotic proteins of the Bcl-2 family. The aim of this study was to determine if GSH, ROS, and Bcl-xL participate in the inhibition of camptothecin-induced apoptosis of moDC by L. mexicana promastigotes. GSH quantification assays showed that camptothecin and BSO (an inhibitor of glutathione synthesis) strongly decreased intracellular GSH concentration in moDC, while infection with L. mexicana promastigotes had no effect in the level of GSH. On the other hand, infection with L. mexicana promastigotes of BSO- and camptothecin-treated moDC diminished the concentration of ROS and induced the expression of the anti-apoptotic protein Bcl-xL. Our findings suggest that inhibition of camptothecin-induced apoptosis of moDC by L. mexicana promastigotes is preferentially regulated by the expression of anti-apoptotic proteins of the Bcl-2 family rather than by the redox status of the cell. FAU - Rodriguez-Gonzalez, Jorge AU - Rodriguez-Gonzalez J AD - Unidad Periferica de Investigacion UNAM-INC, Division de Investigacion, Facultad de Medicina, Universidad Nacional Autonoma de Mexico-Instituto Nacional de Cardiologia "Ignacio Chavez", Juan Badiano No. 1, Col. Belisario Dominguez, Seccion XVI, Delegacion Tlalpan, C.P, 14080, Ciudad de Mexico, Mexico. AD - Posgrado en Ciencias Biologicas, Facultad de Medicina, Unidad de Posgrado, Ciudad Universitaria, 04510, Ciudad de Mexico, Mexico. FAU - Wilkins-Rodriguez, Arturo A AU - Wilkins-Rodriguez AA AD - Unidad Periferica de Investigacion UNAM-INC, Division de Investigacion, Facultad de Medicina, Universidad Nacional Autonoma de Mexico-Instituto Nacional de Cardiologia "Ignacio Chavez", Juan Badiano No. 1, Col. Belisario Dominguez, Seccion XVI, Delegacion Tlalpan, C.P, 14080, Ciudad de Mexico, Mexico. FAU - Gutierrez-Kobeh, Laila AU - Gutierrez-Kobeh L AD - Unidad Periferica de Investigacion UNAM-INC, Division de Investigacion, Facultad de Medicina, Universidad Nacional Autonoma de Mexico-Instituto Nacional de Cardiologia "Ignacio Chavez", Juan Badiano No. 1, Col. Belisario Dominguez, Seccion XVI, Delegacion Tlalpan, C.P, 14080, Ciudad de Mexico, Mexico. lgutierr@unam.mx. LA - eng GR - IN 225116/Papiit, DGAPA, UNAM/ PT - Journal Article DEP - 20180223 PL - Germany TA - Parasitol Res JT - Parasitology research JID - 8703571 RN - 0 (Reactive Oxygen Species) RN - 0 (bcl-X Protein) RN - 5072-26-4 (Buthionine Sulfoximine) RN - GAN16C9B8O (Glutathione) RN - XT3Z54Z28A (Camptothecin) SB - IM MH - Animals MH - Apoptosis/*physiology MH - Buthionine Sulfoximine/pharmacology MH - Camptothecin/pharmacology MH - Cells, Cultured MH - Dendritic Cells/*parasitology/*physiology MH - Down-Regulation MH - Glutathione/*metabolism MH - Humans MH - Leishmania mexicana/*immunology MH - Phosphorylation MH - Reactive Oxygen Species/*metabolism MH - bcl-X Protein/*metabolism OTO - NOTNLM OT - Apoptosis OT - Bcl-xL OT - Dendritic cells OT - Glutathione OT - Leishmania mexicana EDAT- 2018/02/25 06:00 MHDA- 2018/07/11 06:00 CRDT- 2018/02/25 06:00 PHST- 2017/09/20 00:00 [received] PHST- 2018/02/08 00:00 [accepted] PHST- 2018/02/25 06:00 [pubmed] PHST- 2018/07/11 06:00 [medline] PHST- 2018/02/25 06:00 [entrez] AID - 10.1007/s00436-018-5804-z [pii] AID - 10.1007/s00436-018-5804-z [doi] PST - ppublish SO - Parasitol Res. 2018 Apr;117(4):1225-1235. doi: 10.1007/s00436-018-5804-z. Epub 2018 Feb 23.