File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: mTOR plays a critical role in p53-induced oxidative kidney cell injury in HIVAN

TitlemTOR plays a critical role in p53-induced oxidative kidney cell injury in HIVAN
Authors
Issue Date2013
Citation
American Journal of Physiology - Renal Physiology, 2013, v. 305 n. 3, p. F343-F354 How to Cite?
AbstractOxidative stress has been implicated to contribute to HIV-induced kidney cell injury; however, the role of p53, a modulator of oxidative stress, has not been evaluated in the development of HIV-associated nephropathy (HIVAN). We hypothesized that mammalian target of rapamycin (mTOR) may be critical for the induction of p53-mediated oxidative kidney cell injury in HIVAN. To test our hypothesis, we evaluated the effect of an mTOR inhibitor, rapamycin, on kidney cell p53 expression, down stream signaling, and kidney cell injury in both in vivo and in vitro studies. Inhibition of the mTOR pathway resulted in downregulation of renal tissue p53 expression, associated downstream signaling, and decreased number of sclerosed glomeruli, tubular microcysts, and apoptosed and 8-hydroxy deoxyguanosine (8-OHdG)-positive(+ve) cells in Tg26 mice. mTOR inhibition not only attenuated kidney cell expression of p66ShcA and phospho-p66ShcA but also reactivated the redox-sensitive stress response program in the form of enhanced expression of manganese superoxide dismutase (MnSOD) and cata lase. In in vitro studies, the mTOR inhibitor also provided protection against HIV-induced podocyte apoptosis. Moreover, mTOR inhibition downregulated HIV-induced podocyte (HP/HIV) p53 expression. Since HP/HIV silenced for mTOR displayed a lack of expression of p53 as well as attenuated podocyte apoptosis, this suggests that mTOR is critical for kidney cell p53 activation and associated oxidative kidney cell injury in the HIV milieu. © 2013 the American Physiological Society.
Persistent Identifierhttp://hdl.handle.net/10722/195410
ISSN
2008 Impact Factor: 3.89
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorRai, P-
dc.contributor.authorPlagov, A-
dc.contributor.authorLan, X-
dc.contributor.authorChandel, N-
dc.contributor.authorSingh, T-
dc.contributor.authorLederman, R-
dc.contributor.authorAyasolla, KR-
dc.contributor.authorMathieson, PW-
dc.contributor.authorSaleem, MA-
dc.contributor.authorHusain, M-
dc.contributor.authorMalhotra, A-
dc.contributor.authorChander, PN-
dc.contributor.authorSinghal, PC-
dc.date.accessioned2014-02-28T06:12:06Z-
dc.date.available2014-02-28T06:12:06Z-
dc.date.issued2013-
dc.identifier.citationAmerican Journal of Physiology - Renal Physiology, 2013, v. 305 n. 3, p. F343-F354-
dc.identifier.issn0363-6127-
dc.identifier.urihttp://hdl.handle.net/10722/195410-
dc.description.abstractOxidative stress has been implicated to contribute to HIV-induced kidney cell injury; however, the role of p53, a modulator of oxidative stress, has not been evaluated in the development of HIV-associated nephropathy (HIVAN). We hypothesized that mammalian target of rapamycin (mTOR) may be critical for the induction of p53-mediated oxidative kidney cell injury in HIVAN. To test our hypothesis, we evaluated the effect of an mTOR inhibitor, rapamycin, on kidney cell p53 expression, down stream signaling, and kidney cell injury in both in vivo and in vitro studies. Inhibition of the mTOR pathway resulted in downregulation of renal tissue p53 expression, associated downstream signaling, and decreased number of sclerosed glomeruli, tubular microcysts, and apoptosed and 8-hydroxy deoxyguanosine (8-OHdG)-positive(+ve) cells in Tg26 mice. mTOR inhibition not only attenuated kidney cell expression of p66ShcA and phospho-p66ShcA but also reactivated the redox-sensitive stress response program in the form of enhanced expression of manganese superoxide dismutase (MnSOD) and cata lase. In in vitro studies, the mTOR inhibitor also provided protection against HIV-induced podocyte apoptosis. Moreover, mTOR inhibition downregulated HIV-induced podocyte (HP/HIV) p53 expression. Since HP/HIV silenced for mTOR displayed a lack of expression of p53 as well as attenuated podocyte apoptosis, this suggests that mTOR is critical for kidney cell p53 activation and associated oxidative kidney cell injury in the HIV milieu. © 2013 the American Physiological Society.-
dc.languageeng-
dc.relation.ispartofAmerican Journal of Physiology - Renal Physiology-
dc.titlemTOR plays a critical role in p53-induced oxidative kidney cell injury in HIVAN-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1152/ajprenal.00135.2013-
dc.identifier.pmid23678040-
dc.identifier.scopuseid_2-s2.0-84880977590-
dc.identifier.volume305-
dc.identifier.issue3-
dc.identifier.spageF343-
dc.identifier.epageF354-
dc.identifier.isiWOS:000322699000014-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats