PMID- 21242807 OWN - NLM STAT- MEDLINE DCOM- 20110729 LR - 20131121 IS - 1533-4023 (Electronic) IS - 0160-2446 (Linking) VI - 57 IP - 4 DP - 2011 Apr TI - Differential modulation of immunostimulant-triggered NO production by endoplasmic reticulum stress inducers in vascular smooth muscle cells. PG - 434-8 LID - 10.1097/FJC.0b013e31820d9486 [doi] AB - We investigated the effects of endoplasmic reticulum (ER) stress inducers thapsigargin (TG) and tunicamycin (Tm) on immunostimulant lipopolysaccharide/interferon (LPS/IFN)-induced expression of isoform of nitric oxide synthase (iNOS) and nitric oxide (NO) production in vascular smooth muscle cells. LPS/IFN-induced iNOS mRNA expression was markedly enhanced by TG, whereas iNOS mRNA expression was strongly attenuated by Tm. Similarly, production of iNOS protein was markedly upregulated by TG but virtually eliminated by Tm. LPS/IFN-induced guanosine triphosphate cyclohydrolase I mRNA expression was slightly reduced by TG and markedly inhibited by Tm. Similarly, LPS/IFN-mediated induction of cellular biopterin was modestly reduced by TG and markedly inhibited by Tm. TG modestly enhanced LPS/IFN-induced activation of NF-kappaB, whereas Tm had no effect on it. Cellular respiration was reduced by TG and Tm in a concentration-dependent manner, which was confirmed by apoptosis assay. Thus, TG and Tm-induced ER stress and differently modulated NO production through alterations in iNOS expression and activity independently of NF-kappaB activation and caused a similar degree of ER stress-induced apoptosis. FAU - Ohta, Satoshi AU - Ohta S AD - Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi, Japan. FAU - Hattori, Yoshiyuki AU - Hattori Y FAU - Nakanishi, Nobuo AU - Nakanishi N FAU - Sugimoto, Hiroyuki AU - Sugimoto H FAU - Kasai, Kikuo AU - Kasai K LA - eng PT - Journal Article PL - United States TA - J Cardiovasc Pharmacol JT - Journal of cardiovascular pharmacology JID - 7902492 RN - 0 (Lipopolysaccharides) RN - 0 (RNA, Messenger) RN - 11089-65-9 (Tunicamycin) RN - 31C4KY9ESH (Nitric Oxide) RN - 67526-95-8 (Thapsigargin) RN - 82115-62-6 (Interferon-gamma) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 3.5.4.16 (GTP Cyclohydrolase) SB - IM MH - Animals MH - Cell Respiration/drug effects MH - Dose-Response Relationship, Drug MH - Endoplasmic Reticulum/*drug effects/metabolism MH - GTP Cyclohydrolase/drug effects/genetics/metabolism MH - Gene Expression Regulation, Enzymologic/drug effects MH - Interferon-gamma/pharmacology MH - Lipopolysaccharides/pharmacology MH - Male MH - Muscle, Smooth, Vascular/cytology/drug effects/metabolism MH - Nitric Oxide/*biosynthesis MH - Nitric Oxide Synthase Type II/drug effects/genetics/metabolism MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Wistar MH - Thapsigargin/administration & dosage/*pharmacology MH - Tunicamycin/administration & dosage/*pharmacology EDAT- 2011/01/19 06:00 MHDA- 2011/07/30 06:00 CRDT- 2011/01/19 06:00 PHST- 2011/01/19 06:00 [entrez] PHST- 2011/01/19 06:00 [pubmed] PHST- 2011/07/30 06:00 [medline] AID - 10.1097/FJC.0b013e31820d9486 [doi] PST - ppublish SO - J Cardiovasc Pharmacol. 2011 Apr;57(4):434-8. doi: 10.1097/FJC.0b013e31820d9486.