title: CD38 is a key enzyme for the survival of mouse microglial BV2 cells.
abstract: CD38 is a multifunctional enzyme that can not only generate cyclic adenosine diphosphate-ribose (cADPR) - a key Ca(2+) -mobilizing second messenger - by consuming NAD(+), but also hydrolyze extracellular NAD(+). There have been only a small number of studies on the functions of CD38 in the CNS. Brain inflammation plays critical roles in ischemic brain injury and multiple other neurological diseases, in which microglia activation is a key event. In this study we determined the roles of CD38 in the basal survival of mouse BV2 microglia cells by applying CD38 siRNA. Our study found that silencing of CD38 led to significantly decreased survival of the cells. We also found that decreased CD38 levels can lead to apoptosis of the microglial cells, as assessed by flow cytometry-based Annexin V/7-AAD assay, caspase-3 immunostaining and Hoechst staining assays. Our study has further indicated that the CD38 silencing-induced apoptosis is mainly caspase 3-dependent. Collectively, our study has provided the first evidence suggesting that CD38 plays a critical role in the basal survival of microglia, and decreased CD38 can lead to caspase 3-dependent apoptosis of the cells. These results suggest that CD38 may become a therapeutic target for modulating microglial survival in neurological diseases.
authors.affiliation: School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, PR China.
authors.forename: Yingxin
authors.initials: Y
authors.lastname: Ma
authors.forename: Jingwen
authors.initials: J
authors.lastname: Jiang
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Nie
authors.forename: Weiliang
authors.initials: W
authors.lastname: Xia
authors.forename: Jianrong
authors.initials: J
authors.lastname: Liu
authors.forename: Weihai
authors.initials: W
authors.lastname: Ying
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000166:cytology* / Q000201:enzymology / Q000502:physiology; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1; D053148:Caspase 3