PMID- 37914354 OWN - NLM STAT- MEDLINE DCOM- 20231103 LR - 20231103 IS - 1347-5215 (Electronic) IS - 0918-6158 (Linking) VI - 46 IP - 11 DP - 2023 TI - RasGRP2 Attenuates Oxygen Deprivation-Induced Autophagy in Vascular Endothelial Cells. PG - 1512-1516 LID - 10.1248/bpb.b23-00317 [doi] AB - Vascular endothelial cells sustain vascular health through barrier and endocrine functions. Insufficient oxygen supply induces endothelial dysfunction in the pathology of various diseases. In addition, oxygen deprivation reportedly induces endothelial dysfunction via autophagy. Ras guanyl-releasing protein 2 (RasGRP2) has guanosine 5'-diphosphate (GDP)/guanosine 5'-triphosphate (GTP) exchange factor activity and activates Rap1 and R-Ras which belong to the small GTPases. RasGRP2 exerts protective effects against vascular endothelial dysfunction. However, the effect of RasGRP2 on hypoxic stress in vascular endothelial cells has not yet been investigated. We examined the protein expression of hypoxia-inducible factor (HIF)-1alpha, BCL2 interacting protein 3 (BNIP3), and microtubule-associated protein light chain 3beta (LC3beta). We observed that oxygen deprivation increased the expression of HIF-1alpha, BNIP3 and LC3beta II. RasGRP2 suppressed the induction of HIF-1alpha and the subsequent increase in LC3beta II. These findings suggest the possibility that RasGRP2 plays a protective role against endothelial dysfunction by suppressing oxygen deprivation-induced autophagy. FAU - Miyazaki, Shouhei AU - Miyazaki S AD - Faculty of Pharmaceutical Sciences, Hiroshima International University. FAU - Takino, Jun-Ichi AU - Takino JI AD - Faculty of Pharmaceutical Sciences, Hiroshima International University. FAU - Nagamine, Kentaro AU - Nagamine K AD - Faculty of Health Sciences, Hiroshima International University. FAU - Hori, Takamitsu AU - Hori T AD - Faculty of Pharmaceutical Sciences, Hiroshima International University. LA - eng PT - Journal Article PL - Japan TA - Biol Pharm Bull JT - Biological & pharmaceutical bulletin JID - 9311984 RN - S88TT14065 (Oxygen) RN - 0 (Guanine Nucleotide Exchange Factors) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) SB - IM MH - *Endothelial Cells/metabolism MH - *Oxygen/metabolism MH - Guanine Nucleotide Exchange Factors MH - Microtubule-Associated Proteins/metabolism MH - Autophagy MH - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism MH - Cell Hypoxia OTO - NOTNLM OT - Ras guanyl-releasing protein 2 OT - autophagy OT - endothelial cell OT - hypoxia OT - hypoxia-inducible factor-1alpha EDAT- 2023/11/02 00:42 MHDA- 2023/11/03 06:43 CRDT- 2023/11/01 21:05 PHST- 2023/11/03 06:43 [medline] PHST- 2023/11/02 00:42 [pubmed] PHST- 2023/11/01 21:05 [entrez] AID - 10.1248/bpb.b23-00317 [doi] PST - ppublish SO - Biol Pharm Bull. 2023;46(11):1512-1516. doi: 10.1248/bpb.b23-00317.