Nicotinamide riboside (NR) is one of the orally bioavailable NAD+ precursors and has been demonstrated to exhibit beneficial effects against aging and aging-associated diseases. However, the metabolic pathway of NR in vivo is not yet fully understood. Here, we demonstrate that orally administered NR increases NAD+ level via two different pathways. In the early phase, NR was directly absorbed and contributed to NAD+ generation through the NR salvage pathway, while in the late phase, NR was hydrolyzed to nicotinamide (NAM) by bone marrow stromal cell antigen 1 (BST1), and was further metabolized by the gut microbiota to nicotinic acid, contributing to generate NAD+ through the Preiss-Handler pathway. Furthermore, we report BST1 has a base-exchange activity against both NR and nicotinic acid riboside (NAR) to generate NAR and NR, respectively, connecting amidated and deamidated pathways. Thus, we conclude that BST1 plays a dual role as glycohydrolase and base-exchange enzyme during oral NR supplementation.
ADP-ribosyl Cyclase/metabolism , Antigens, CD/metabolism , Glycoside Hydrolases/metabolism , Niacinamide/analogs & derivatives , Pyridinium Compounds/pharmacokinetics , A549 Cells , ADP-ribosyl Cyclase/genetics , Administration, Oral , Aging/drug effects , Animals , Antigens, CD/genetics , Dietary Supplements , GPI-Linked Proteins/genetics , GPI-Linked Proteins/metabolism , Gastrointestinal Microbiome , Glycoside Hydrolases/genetics , Humans , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Intestine, Small/metabolism , Intestine, Small/microbiology , Mice , Mice, Knockout , Niacin/metabolism , Niacinamide/administration & dosage , Niacinamide/metabolism , Niacinamide/pharmacokinetics , Pentosyltransferases/genetics , Pentosyltransferases/metabolism , Pyridinium Compounds/administration & dosage
PURPOSE: To report 2 cases of central retinal artery occlusion (CRAO) who underwent retinal endovascular surgery with injection of tissue plasminogen activator (tPA) into the retinal artery and showed a remarkable improvement in visual acuity and retinal circulation. METHODS: Standard 25-G vitrectomy was performed under local anesthesia. Simultaneously, tPA (80,000 units/mL) solution was injected into the retinal artery of the optic disc for 2-3 min using a microneedle. Changes in visual acuity, fundus photography, optical coherence tomography (OCT), fluorescein angiography, and laser speckle flowgraphy (LSFG) results were examined. RESULTS: Both cases could be treated within 12 h after the onset of CRAO. Case 1 was a 47-year-old woman. Her visual acuity improved from counting fingers before operation to 0.08 logMAR 1 month after the surgery. However, thinning of the retina at the macula was observed by OCT. Case 2 was a 70-year-old man. His visual acuity improved from counting fingers to 0.1 logMAR 2 months after the surgery. Both fluorescein angiography and LSFG showed improvement in retinal circulation after the surgery in case 2. CONCLUSIONS: Retinal endovascular surgery with injection of tPA into the retinal artery was feasible and may be a way to improve visual acuity and retinal circulation when performed in the acute phase of CRAO.
