Cellular osmolytes reduce lens epithelial cell death and alleviate cataract formation in galactosemic rats.

作者: Michael L. Mulhern , Peter F. Kador , Toshimichi Shinohara , Christian J. Madson , James Randazzo

DOI:

关键词:

摘要: Purpose Many cataractogenic stresses also induce endoplasmic reticulum (ER) stress in lens epithelial cells (LECs), which appears to be one of the universal inducers cell death. In galactosemic rats, activation ER results unfolded protein response (UPR)-dependent death pathway, production reactive oxygen species (ROS), and All are induced precede cataract formation. Cellular osmolytes such as 4-phenylbutyric acid (PBA), trimethylamine N-oxide (TMAO), tauroursodeoxychoric (TUDCA) known suppress induction stress. We investigated whether these small molecules prevent formation galactose-fed rat lenses. Methods Cultured LECs were treated with galactose each cellular osmolyte. Sprague-Dawley rats fed a 50% chow for 15 days or without osmolyte treatment. Similarly, selenite was injected subcutaneously into osmolytes. Calcein AM ethidium homodimer-1 (EthD) used detect live dead cells, respectively. The osmolytes, PBA, TMAO, TUDCA tested their ability LEC Results rescued cultured human stressors. administered either orally by injection rats. These had significantly reduced partially delayed hypermature Since UPR not activated selenite, we nuclear UPR-independent pathway control. selenite-induced did alleviate Conclusions further establish that play vital role certain types addition, may potential prophylactic drugs some cataracts.

参考文章(78)
Julien Averous, Anne-Catherine Maurin, Alain Bruhat, Céline Jousse, Céline Arliguie, Pierre Fafournoux, Induction of IGFBP-1 expression by amino acid deprivation of HepG2 human hepatoma cells involves both a transcriptional activation and an mRNA stabilization due to its 3′UTR FEBS Letters. ,vol. 579, pp. 2609- 2614 ,(2005) , 10.1016/J.FEBSLET.2005.03.077
William J. Welch, C. Randell Brown, Influence of molecular and chemical chaperones on protein folding Cell Stress & Chaperones. ,vol. 1, pp. 109- 115 ,(1996) , 10.1379/1466-1268(1996)001<0109:IOMACC>2.3.CO;2
Kengo Ikesugi, Ryoko Yamamoto, Michael L. Mulhern, Toshimichi Shinohara, Role of the unfolded protein response (UPR) in cataract formation Experimental Eye Research. ,vol. 83, pp. 508- 516 ,(2006) , 10.1016/J.EXER.2006.01.033
Diyaa Rachdan, Marjorie F. Lou, John J. Harding, Glutathione Reductase from Human Cataract Lenses can be Revived by Reducing Agents and by a Molecular Chaperone, α -Crystallin Current Eye Research. ,vol. 30, pp. 919- 925 ,(2005) , 10.1080/02713680590953110
K Zu, T Bihani, A Lin, Y-M Park, K Mori, C Ip, Enhanced selenium effect on growth arrest by BiP/GRP78 knockdown in p53-null human prostate cancer cells. Oncogene. ,vol. 25, pp. 546- 554 ,(2006) , 10.1038/SJ.ONC.1209071
Brian J. Bennion, Mari L. DeMarco, Valerie Daggett, Preventing Misfolding of the Prion Protein by Trimethylamine N-Oxide† Biochemistry. ,vol. 43, pp. 12955- 12963 ,(2004) , 10.1021/BI0486379
Frank J. Giblin, Victor R. Leverenz, Vanita A. Padgaonkar, Nalin J. Unakar, Loan Dang, Li-Ren Lin, Marjorie F. Lou, Venkat N. Reddy, Douglas Borchman, James P. Dillon, UVA light in vivo reaches the nucleus of the guinea pig lens and produces deleterious, oxidative effects. Experimental Eye Research. ,vol. 75, pp. 445- 458 ,(2002) , 10.1006/EXER.2002.2039
Jean-Pierre Morello, Michel Bouvier, Ulla E. Petäjä-Repo, Daniel G. Bichet, Pharmacological chaperones: a new twist on receptor folding Trends in Pharmacological Sciences. ,vol. 21, pp. 466- 469 ,(2000) , 10.1016/S0165-6147(00)01575-3
Philippe Podevin, Olivier Rosmorduc, Filomena Conti, Yvon Calmus, Peter J. Meier, Raoul Poupon, Bile acids modulate the interferon signalling pathway. Hepatology. ,vol. 29, pp. 1840- 1847 ,(1999) , 10.1002/HEP.510290617
Masahiko Ayaki, Nobuyuki Ohoguro, Noriyuki Azuma, Yoshinao Majima, Kiyomi Yata, Nobuhiro Ibaraki, Dhirendra P. Singh, Vincent Ko, Toshimichi Shinohara, Detection of cytotoxic anti-LEDGF autoantibodies in atopic dermatitis. Autoimmunity. ,vol. 35, pp. 319- 327 ,(2002) , 10.1080/0891693021000003198