Oxidative activation of type III CD38 by NADPH oxidase-derived hydrogen peroxide in Ca2+ signaling
- 주제(키워드) cADPR , ROS , LAK cells , Nox4 , ADP-ribosyl cyclase
- 주제(기타) Biochemistry & Molecular Biology; Biology; Cell Biology
- 설명문(일반) [Park, Dae-Ryoung; Nam, Tae-Sik; Kim, Ye-Won; Kim, Uh-Hyun] Chonbuk Natl Univ, Med Sch, Dept Biochem, Jeonju 561182, South Korea; [Park, Dae-Ryoung; Nam, Tae-Sik; Kim, Ye-Won; Kim, Uh-Hyun] Chonbuk Natl Univ, Med Sch, Natl Creat Res Lab Ca2 Signaling Network, Jeonju, South Korea; [Kim, Uh-Hyun] Chonbuk Natl Univ, Med Sch, Inst Cardiovasc Res, Jeonju, South Korea; [Bae, Yun Soo] Ewha Womans Univ, Coll Nat Sci, Dept Life Sci, Seoul, South Korea
- 등재 SCIE, SCOPUS
- OA유형 Bronze
- 발행기관 FEDERATION AMER SOC EXP BIOL
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000159807
- 본문언어 영어
- Published As http://dx.doi.org/10.1096/fj.201800235R
- PubMed https://pubmed.ncbi.nlm.nih.gov/30452880
초록/요약
Reactive oxygen species (ROS) derived from NADPH oxidase (Nox) has been shown to activate ADP-ribosyl cyclase (ARC), which produces the Ca2+ mobilizing second messenger, cyclic ADP-ribose (cADPR). In the present study, we examined how ROS activates cluster of differentiation (CD)38, a mammalian prototype of ARC. CD38 exists in type II and III forms with opposing membrane orientation. This study showed the coexpression of type II and III CD38 in lymphokine-activated killer (LAK) cells. The catalytic site of the constitutively active type II CD38 faces the outside of the cell or the inside of early endosomes (EEs), whereas the basally inactive type III CD38 faces the cytosol. Type III CD38 interacted with Nox4/phosphorylated-p22phox (p-p22phox) in EEs of LAK cells upon IL-8 treatment. H2O2 derived from Nox4 activated type III CD38 by forming a disulfide bond between Cys164 and Cys177, resulting in increased cADPR formation. Our study identified the mechanism by which type III CD38 is activated in an immune cell (LAK), in which H2O2 generated by Nox4 oxidizes and activates type III CD38 to generate cADPR. These findings provide a novel model of cross-talk between ROS and Ca2+ signaling.Park, D.-R., Nam, T.-S., Kim, Y.-W., Bae, Y. S., Kim, U.-H. Oxidative activation of type III CD38 by NADPH oxidase-derived hydrogen peroxide in Ca2+ signaling.
more