Prevention of HIV protease inhibitor-induced dysregulation of hepatic lipid metabolism by raltegravir via endoplasmic reticulum stress signaling pathways

Journal of Pharmacology and Experimental Therapeutics

Volumn 334, Issue 2, 2010, Pages 530-539

  Cao, Risheng ^a   Hu, Yiqiao ^a   Wang, Yun ^b,c   Gurley, Emily C ^b   Studer, Elaine J ^b   Wang, Xuan ^b   Hylemon, Phillip B ^b   Pandak, William M ^b   Sanyal, Arun J ^b   Zhang, Luyong ^c   Zhou, Huiping ^b  

^a NANJING UNIVERSITY   (China)

^b VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

^c CHINA PHARMACEUTICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; CHOLESTEROL; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LOPINAVIR PLUS RITONAVIR; LOW DENSITY LIPOPROTEIN CHOLESTEROL; RALTEGRAVIR; TRIACYLGLYCEROL;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DISEASE EXACERBATION; DRUG EFFECT; DYSLIPIDEMIA; ENDOPLASMIC RETICULUM STRESS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; IN VITRO STUDY; IN VIVO STUDY; LIPID METABOLISM; LIPID STORAGE; LIVER CELL; LIVER METABOLISM; LIVER TOXICITY; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; RAT; SIGNAL TRANSDUCTION;

ANIMALS; APOPTOSIS; CELLS, CULTURED; DRUG ANTAGONISM; ENDOPLASMIC RETICULUM; HEPATOCYTES; HIV INTEGRASE INHIBITORS; HIV PROTEASE INHIBITORS; HYPERLIPIDEMIAS; LIPID METABOLISM; LIVER; MALE; MICE; MICE, INBRED C57BL; PYRIMIDINONES; PYRROLIDINONES; RATS; RITONAVIR; SIGNAL TRANSDUCTION;

EID: 77954940839     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.110.168484     Document Type: Article

References (38)

1. 2008. Raltegravir phase III study data released. AIDS Patient Care STDS 22:917.
2. Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, and Bacon BR (1999) Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 94:2467-2474.
3. Carr A, Hudson J, Chuah J, Mallal S, Law M, Hoy J, Doong N, French M, Smith D, Cooper DA, and PIILR Study Group (2001) HIV protease inhibitor substitution in patients with lipodystrophy: a randomized, controlled, open-label, multicentre study. AIDS 15:1811-1822. (Pubitemid 32939242)
4. Chinta SJ, Poksay KS, Kaundinya G, Hart M, Bredesen DE, Andersen JK, and Rao RV (2009) Endoplasmic reticulum stress-induced cell death in dopaminergic cells: effect of resveratrol. J Mol Neurosci 39:157-168.
5. Cocohoba J and Dong BJ (2008) Raltegravir: the first HIV integrase inhibitor. Clin Ther 30:1747-1765.
6. Dayam R, Al-Mawsawi LQ, and Neamati N (2007) HIV-1 integrase inhibitors: an emerging clinical reality. Drugs R D 8:155-168. (Pubitemid 46707839)
7. Djedaini M, Peraldi P, Drici MD, Darini C, Saint-Marc P, Dani C, and Ladoux A (2009) Lopinavir co-induces insulin resistance and ER stress in human adipocytes. Biochem Biophys Res Commun 386:96-100.
8. Elbasha EE, Szucs T, Chaudhary MA, Kumar RN, Roediger A, Cook JR, and Opravil M (2009) Cost-effectiveness of raltegravir in antiretroviral treatment-experienced HIV-1-infected patients in Switzerland. HIV Clin Trials 10:233-253.
9. Erickson SK (2009) Nonalcoholic fatty liver disease. J Lipid Res 50 (Suppl):S412-S416.
10. Feng B, Yao PM, Li Y, Devlin CM, Zhang D, Harding HP, Sweeney M, Rong JX, Kuriakose G, Fisher EA, et al. (2003) The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages. Nat Cell Biol 5:781-792.
11. Folch J, Lees M, and Stanley GHS (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497-509.
12. Hruz PW, Murata H, Qiu H, and Mueckler M (2002) Indinavir induces acute and reversible peripheral insulin resistance in rats. Diabetes 51:937-942.
13. Hughes CA, Robinson L, Tseng A, and MacArthur RD (2009) New antiretroviral drugs: a review of the efficacy, safety, pharmacokinetics, and resistance profile of tipranavir, darunavir, etravirine, rilpivirine, maraviroc, and raltegravir. Expert Opin Pharmacother 10:2445-2466.
14. Imaz A, del Saz SV, Ribas MA, Curran A, Caballero E, Falcó V, Crespo M, Ocaña I, Diaz M, de Gopegui ER, et al. (2009) Raltegravir, etravirine, and ritonavir-boosted darunavir: a safe and successful rescue regimen for multidrug-resistant HIV-1 infection. J Acquir Immune Defic Syndr 52:382-386.
15. Iwamoto M, Wenning LA, Mistry GC, Petry AS, Liou SY, Ghosh K, Breidinger S, Azrolan N, Gutierrez MJ, Bridson WE, et al. (2008a) Atazanavir modestly increases plasma levels of raltegravir in healthy subjects. Clin Infect Dis 47:137-140.
16. Iwamoto M, Wenning LA, Petry AS, Laethem M, De Smet M, Kost JT, Breidinger SA, Mangin EC, Azrolan N, Greenberg HE, et al. (2008b) Minimal effects of ritonavir and efavirenz on the pharmacokinetics of raltegravir. Antimicrob Agents Chemother 52:4338-4343.
17. Iwamoto M, Wenning LA, Petry AS, Laethem M, De Smet M, Kost JT, Merschman SA, Strohmaier KM, Ramael S, Lasseter KC, et al. (2008c) Safety, tolerability, and pharmacokinetics of raltegravir after single and multiple doses in healthy subjects. Clin Pharmacol Ther 83:293-299.
18. Kaplowitz N, Than TA, Shinohara M, and Ji C (2007) Endoplasmic reticulum stress and liver injury. Semin Liver Dis 27:367-377.
19. Kassahun K, McIntosh I, Cui D, Hreniuk D, Merschman S, Lasseter K, Azrolan N, Iwamoto M, Wagner JA, and Wenning LA (2007) Metabolism and disposition in humans of raltegravir (MK-0518), an anti-AIDS drug targeting the human immunodeficiency virus 1 integrase enzyme. Drug Metab Dispos 35:1657-1663.
20. Koster JC, Remedi MS, Qiu H, Nichols CG, and Hruz PW (2003) HIV protease inhibitors acutely impair glucose-stimulated insulin release. Diabetes 52:1695-1700. (Pubitemid 36792459)
21. Lee GA, Rao M, Mulligan K, Lo JC, Aweeka F, Schwarz JM, Schambelan M, and Grunfeld C (2007) Effects of ritonavir and amprenavir on insulin sensitivity in healthy volunteers. Aids 21:2183-2190.
22. Mallon PW, Cooper DA, and Carr A (2001) HIV-associated lipodystrophy. HIV Med 2:166-173.
23. Moyle G and Carr A (2002) HIV-associated lipodystrophy, metabolic complications, and antiretroviral toxicities. HIV Clin Trials 3:89-98. (Pubitemid 34183098)
24. Murata H, Hruz PW, and Mueckler M (2002) Indinavir inhibits the glucose transporter isoform Glut4 at physiologic concentrations. AIDS 16:859-863.
25. Nair V and Chi G (2007) HIV integrase inhibitors as therapeutic agents in AIDS. Rev Med Virol 17:277-295.
26. Parker RA, Flint OP, Mulvey R, Elosua C, Wang F, Fenderson W, Wang S, Yang WP, and Noor MA (2005) Endoplasmic reticulum stress links dyslipidemia to inhibition of proteasome activity and glucose transport by HIV protease inhibitors. Mol Pharmacol 67:1909-1919.
27. Poirier JM, Robidou P, and Jaillon P (2008) Quantification of the HIV-integrase inhibitor raltegravir (MK-0518) in human plasma by high-performance liquid chromatography with fluorescence detection. J Chromatogr B Analyt Technol Biomed Life Sci 867:277-281.
28. Riddle TM, Kuhel DG, Woollett LA, Fichtenbaum CJ, and Hui DY (2001) HIV protease inhibitor induces fatty acid and sterol biosynthesis in liver and adipose tissues due to the accumulation of activated sterol regulatory element-binding proteins in the nucleus. J Biol Chem 276:37514-37519.
29. Spector AA (2006) HIV protease inhibitors and hyperlipidemia: a fatty acid connection. Arterioscler Thromb Vasc Biol 26:7-9.
30. Steigbigel RT, Cooper DA, Kumar PN, Eron JE, Schechter M, Markowitz M, Loutfy MR, Lennox JL, Gatell JM, Rockstroh JK, et al. (2008) Raltegravir with optimized background therapy for resistant HIV-1 infection. N Engl J Med 359:339-354.
31. Szegezdi E, Duffy A, O'Mahoney ME, Logue SE, Mylotte LA, O'Brien T, and Samali A (2006) ER stress contributes to ischemia-induced cardiomyocyte apoptosis. Biochem Biophys Res Commun 349:1406-1411.
32. Wang N and Tall AR (2003) Regulation and mechanisms of ATP-binding cassette transporter A1-mediated cellular cholesterol efflux. Arterioscler Thromb Vasc Biol 23:1178-1184.
33. Wu X, Sun L, Zha W, Studer E, Gurley E, Chen L, Wang X, Hylemon PB, Pandak WM, Jr., Sanyal AJ, Zhang L, Wang G, Chen J, Wang JY, and Zhou H (2010) HIV protease inhibitors induce endoplasmic reticulum stress and disrupt barrier integrity in intestinal epithelial cells. Gastroenterology 138:197-209.
34. Wu X, Zhang L, Gurley E, Studer E, Shang J, Wang T, Wang C, Yan M, Jiang Z, Hylemon PB, et al. (2008) Prevention of free fatty acid-induced hepatic lipotoxicity by 18beta-glycyrrhetinic acid through lysosomal and mitochondrial pathways. Hepatology 47:1905-1915.
35. Zhang K, Shen X, Wu J, Sakaki K, Saunders T, Rutkowski DT, Back SH, and Kaufman RJ (2006) Endoplasmic reticulum stress activates cleavage of CREBH to induce a systemic inflammatory response. Cell 124:587-599.
36. Zhou H, Gurley EC, Jarujaron S, Ding H, Fang Y, Xu Z, Pandak WM Jr, and Hylemon PB (2006) HIV protease inhibitors activate the unfolded protein response and disrupt lipid metabolism in primary hepatocytes. Am J Physiol Gastrointest Liver Physiol 291:G1071-1080.
37. Zhou H, Jarujaron S, Gurley EC, Chen L, Ding H, Studer E, Pandak WM Jr, Hu W, Zou T, Wang JY, et al. (2007) HIV protease inhibitors increase TNF-alpha and IL-6 expression in macrophages: involvement of the RNA-binding protein HuR. Atherosclerosis 195:e134-e143.
38. Zhou H, PandakWMJr, Lyall V, Natarajan R, and Hylemon PB (2005) HIV protease inhibitors activate the unfolded protein response in macrophages: implication for atherosclerosis and cardiovascular disease. Mol Pharmacol 68:690-700.