Gene interactions and pathways from curated databases and text-mining
American journal of physiology. Renal physiology 2013, PMID: 23678040

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

Rai, Partab; Plagov, Andrei; Lan, Xiqian; Chandel, Nirupama; Singh, Tejinder; Lederman, Rivka; Ayasolla, Kamesh R; Mathieson, Peter W; Saleem, Moin A; Husain, Mohammad; Malhotra, Ashwani; Chander, Praveen N; Singhal, Pravin C

Oxidative 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, downstream 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 catalase. 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.

Diseases/Pathways annotated by Medline MESH: AIDS-Associated Nephropathy, Acute Kidney Injury, HIV Infections
Document information provided by NCBI PubMed

Text Mining Data

p53 — mTOR: " To test our hypothesis, we evaluated the effect of an mTOR inhibitor, rapamycin, on kidney cell p53 expression, downstream signaling, and kidney cell injury in both in vivo and in vitro studies "

p53 → mTOR: " 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 "

Manually curated Databases

No curated data.