Hantaan virus replication is promoted via AKT activated mitochondria OXPHOS

Oxidative phosphorylation (OXPHOS) is a vital pathway provides ATP for intracellular activities. Here, we found that Hantaan virus (HTNV) exploited mitochondria OXPHOS to assist its replication in host cells and Protein Kinase B/AKT played a major function in this process. Inhibiting AKT activation by BEZ treatment can inhibit HTNV replication and prevent the increase of OXPHOS level caused by HTNV infection. We also found that HTNV infection can promote AKT translocation to mitochondria, where AKT phosphorylates Polynucleotide phosphorylase (PNPT). Taken together, our research demonstrates that HTNV replication exploits OXPHOS in host cells and it increases OXPHOS function by AKT-PNPT interaction in mitochondria.

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Preferential Dependence of Breast Cancer Cells versus Normal Cells on Integrin-Linked Kinase for Protein Kinase B/Akt Activation and Cell Survival

Cancer Research ◽

10.1158/0008-5472.can-05-2304 ◽

2006 ◽

Vol 66 (1) ◽

pp. 393-403 ◽

Cited By ~ 85

Author(s):

Armelle A. Troussard ◽

Paul C. McDonald ◽

Elizabeth D. Wederell ◽

Nasrin M. Mawji ◽

Nolan R. Filipenko ◽

...

Keyword(s):

Breast Cancer ◽

Protein Kinase ◽

Cell Survival ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Protein Kinase B ◽

Normal Cells ◽

Akt Activation ◽

Integrin Linked Kinase

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Chronic Protein Kinase B (PKB/c-akt) Activation Leads to Apoptosis Induced by Oxidative Stress–Mediated Foxo3a Transcriptional Up-regulation

Cancer Research ◽

10.1158/0008-5472.can-06-1111 ◽

2006 ◽

Vol 66 (22) ◽

pp. 10760-10769 ◽

Cited By ~ 45

Author(s):

Ankie G.M. van Gorp ◽

Karen M. Pomeranz ◽

Kim U. Birkenkamp ◽

Rosaline C-Y. Hui ◽

Eric W-F. Lam ◽

...

Keyword(s):

Oxidative Stress ◽

Protein Kinase ◽

Protein Kinase B ◽

Akt Activation

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Pharmacological Exploitation of the α1-Adrenoreceptor Antagonist Doxazosin to Develop a Novel Class of Antitumor Agents That Block Intracellular Protein Kinase B/Akt Activation

Journal of Medicinal Chemistry ◽

10.1021/jm049752k ◽

2004 ◽

Vol 47 (18) ◽

pp. 4453-4462 ◽

Cited By ~ 37

Author(s):

Yeng-Jeng Shaw ◽

Ya-Ting Yang ◽

Jason B. Garrison ◽

Natasha Kyprianou ◽

Ching-Shih Chen

Keyword(s):

Protein Kinase ◽

Antitumor Agents ◽

Protein Kinase B ◽

Intracellular Protein ◽

Akt Activation

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Heparanase Induces Endothelial Cell Migration via Protein Kinase B/Akt Activation

Journal of Biological Chemistry ◽

10.1074/jbc.m400554200 ◽

2004 ◽

Vol 279 (22) ◽

pp. 23536-23541 ◽

Cited By ~ 158

Author(s):

Svetlana Gingis-Velitski ◽

Anna Zetser ◽

Moshe Y. Flugelman ◽

Israel Vlodavsky ◽

Neta Ilan

Keyword(s):

Cell Migration ◽

Endothelial Cell ◽

Protein Kinase ◽

Protein Kinase B ◽

Endothelial Cell Migration ◽

Akt Activation

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Protein kinase B/Akt modulates nephrotoxicant-induced necrosis in renal cells

AJP Renal Physiology ◽

10.1152/ajprenal.00082.2006 ◽

2007 ◽

Vol 292 (1) ◽

pp. F292-F303 ◽

Cited By ~ 15

Author(s):

Zabeena P. Shaik ◽

E. Kim Fifer ◽

Grażyna Nowak

Keyword(s):

Protein Kinase ◽

Kinase Inhibitor ◽

Protein Kinase B ◽

Primary Cultures ◽

Protective Role ◽

Dominant Negative ◽

Protective Effects ◽

Atp Content ◽

Akt Activation ◽

Atp Levels

Protein kinase B (Akt) activation is well known for its protective effects against apoptosis. However, the role of Akt in regulation of necrosis is unknown. This study was designed to test whether Akt activation protects against nephrotoxicant-induced injury and death in renal proximal tubular cells (RPTC). Exposure of primary cultures of RPTC to the nephrotoxic cysteine conjugate, S-(1,2-dichlorovinyl)-l-cysteine (DCVC), resulted in 9% apoptosis and 30% necrosis at 24 h following the exposure. Akt was activated during 8 h but not at 24 h following toxicant exposure. No RPTC necrosis was observed during Akt activation. Blocking Akt activation using a phosphatidylinositol 3-kinase inhibitor, LY294002 (20 μM), or expressing dominant negative (inactive) Akt increased DCVC-induced RPTC necrosis to 42%. In contrast, Akt activation by expression of constitutively active Akt diminished necrosis to 15%. Modulation of Akt activity had no effect on DCVC-induced apoptosis. DCVC-induced RPTC injury was accompanied by decreases in respiration (51% of controls) and ATP levels (57% of controls). Akt inhibition exacerbated decreases in RPTC respiration and intracellular ATP content (both to 30% of controls). In contrast, Akt activation reduced DCVC-induced decreases in respiration (80% of controls) and prevented decline in ATP content. These data show that in RPTC, Akt activation reduces 1) toxicant-induced mitochondrial dysfunction, 2) decreases in ATP levels, and 3) necrosis. We conclude that Akt activation plays a protective role against necrosis caused by nephrotoxic insult in RPTC. Furthermore, we identified mitochondria as a subcellular target of protective actions of Akt against necrosis.

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