title: NAD⁺-carrying mesoporous silica nanoparticles can prevent oxidative stress-induced energy failures of both rodent astrocytes and PC12 cells.
abstract: OBJECTIVE
  To test the hypothesis that NAD(+)-carrying mesoporous silica nanoparticles (M-MSNs@NAD+) can effectively deliver NAD(+) into cells to produce cytoprotective effects.
  
  
  METHODS
  NAD(+) was incorporated into M-MSNs. Primary rat astrocyte cultures and PC12 cells were treated with H₂O₂, followed by post-treatment with M-MSNs@NAD+. After various durations of the post-treatment, intracellular NAD(+) levels, intracellular ATP levels and lactate dehydrogenase (LDH) release were determined.
  
  
  CONCLUSIONS
  M-MSNs can be effectively loaded with NAD(+). The M-MSNs@NAD+ can significantly attenuate H₂O₂-induced NAD(+) and ATP decreases in both astrocyte cultures and PC12 cells. M-MSNs@NAD+ can also partially prevent the H₂O₂-induced LDH release from both astrocyte cultures and PC12 cells. In contrast, the NAD(+) that is spontaneously released from the M-MSNs@NAD+ is insufficient to prevent the H₂O₂-induced damage.
  
  
  CONCLUSIONS
  Our study has suggested the first approach that can effectively deliver NAD(+) into cells, which provides an important basis both for elucidating the roles of intracellular NAD(+) in biological functions and for therapeutic applications of NAD(+). Our study has also provided the first direct evidence demonstrating a key role of NAD(+) depletion in oxidative stress-induced ATP decreases.
authors.affiliation: School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Heyu
authors.initials: H
authors.lastname: Chen
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.forename: Jixi
authors.initials: J
authors.lastname: Zhang
authors.forename: Yingxin
authors.initials: Y
authors.lastname: Ma
authors.forename: Caixia
authors.initials: C
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Hongchen
authors.initials: H
authors.lastname: Gu
authors.forename: Weihai
authors.initials: W
authors.lastname: Ying
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D016923:Cell Death; D004734:Energy Metabolism / Q000187:drug effects; D004789:Enzyme Activation; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D058185:Magnetite Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D009243:NAD / Q000737:chemistry* / Q000378:metabolism; D018384:Oxidative Stress; D016716:PC12 Cells; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D016062:Porosity; D051381:Rats; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D058185:Magnetite Nanoparticles; D009243:NAD; D012822:Silicon Dioxide; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D011065:Poly(ADP-ribose) Polymerases
references.citation: Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12227-32
references.pmid: 11593040
references.citation: Gerontology. 1997;43(4):242-53
references.pmid: 9222753
references.citation: J Biol Chem. 2004 Apr 30;279(18):18895-902
references.pmid: 14960594
references.citation: Annu Rev Pharmacol Toxicol. 2001;41:317-45
references.pmid: 11264460
references.citation: J Neurotrauma. 2012 May 1;29(7):1401-9
references.pmid: 22352983
references.citation: Purinergic Signal. 2007 Mar;3(1-2):71-81
references.pmid: 18404420
references.citation: Biomaterials. 2011 Dec;32(35):9546-56
references.pmid: 21906804
references.citation: Antioxid Redox Signal. 2008 Feb;10(2):179-206
references.pmid: 18020963
references.citation: Neurosci Lett. 2012 Mar 23;512(2):67-71
references.pmid: 22260797
references.citation: Nanobiotechnology. 2007 May 1;3(2):89-95
references.pmid: 19936038
references.citation: J Neurochem. 1999 Oct;73(4):1549-56
references.pmid: 10501200
references.citation: Nanoscale. 2012 Jun 7;4(11):3415-21
references.pmid: 22543531
references.citation: J Am Chem Soc. 2006 Dec 13;128(49):15582-3
references.pmid: 17147355
references.citation: J Colloid Interface Sci. 2011 Sep 1;361(1):16-24
references.pmid: 21689824
references.citation: Front Biosci. 2007 Jan 01;12:2728-34
references.pmid: 17127275
references.citation: J Biol Chem. 2003 May 16;278(20):18426-33
references.pmid: 12626504
references.citation: Cell Physiol Biochem. 2007;20(1-4):45-54
references.pmid: 17595514
references.citation: Neuroreport. 2000 May 15;11(7):1385-8
references.pmid: 10841343
references.citation: Curr Med Chem. 2010;17(20):2152-8
references.pmid: 20423305
references.citation: J Basic Clin Physiol Pharmacol. 1995;6(3-4):205-28
references.pmid: 8852268
references.citation: J Control Release. 2008 Jun 4;128(2):157-64
references.pmid: 18439699
references.citation: J Neurochem. 2002 Jul;82(1):19-29
references.pmid: 12091461
references.citation: ACS Nano. 2008 May;2(5):889-96
references.pmid: 19206485
references.citation: Pharmacol Rev. 2002 Sep;54(3):375-429
references.pmid: 12223530
references.citation: J Neurosci. 2010 Feb 24;30(8):2967-78
references.pmid: 20181594
references.citation: Angew Chem Int Ed Engl. 2008;47(44):8438-41
references.pmid: 18726979
references.citation: Biochem Biophys Res Commun. 2003 Sep 5;308(4):809-13
references.pmid: 12927790