Age-related decline in expression of calnexin

Abstract

Abbreviations: ER, endoplasmic reticulum; ESI Q-TOF MS, electrospray ionization quadupole-time of flight mass spectrometry; HDF, human diploid fibroblast; HSP, heat shock protein; MALDI-TOF MS, matrix-assisted laser desorption/ionization-time of flight mass spectrometry A bstractA g ing is accom p an ied b y th e changes in the cells that decrease their capacity to respo nd to vario us form s of stress. C ells are kn ow n to respond to stresses through expression of stressresp onse pro teins, h eat-sho ck p rotein s co mposed o f m olecular ch aperones. R ecent studies suggest that chaperone level and stress-induced chaperone exp ression cou ld decrease w ith agin g . T h e aim o f th e p resen t stu d y is to id en tify chaperones that sh ow a sign ificant change in pro tein expressio n w ith ag ing. W e u sed an in vitro ag ing m od el system o f h um an diplo id fib ro b la s ts (H D F ). P ro te o m e a n a ly s is o f H D F show ed that endoplasm ic reticulum (ER ) chaperon e, calnexin, significan tly d ecreased w ith aging. O xidative stress-induced expressio n of calnexin also attenuated in o ld H D F com p ared to youn g cells. T hese find ings sugg est caln exin decreases w ith aging and m ight contribute to a cytoprotection in a variety of hum an age-related diseases.

The unfolded protein response and cellular senescence. A Review in the Theme: Cellular Mechanisms of Endoplasmic Reticulum Stress Signaling in Health and Disease

“…Similar opposed results are available for the IRE1␣/XBP1 branch. An increase of the XBP1s spliced form was reported in adryamycin-induced senescence in lymphomas cells (38), whereas the expression of the XBP1s target gene calnexin is decreased during replicative senescence of human dermal fibroblasts (24,75).…”

“…The analysis of the data from these studies does not highlight any differences regarding the cell type. For example, increased expression of several ER chaperones were Themes C418 ER STRESS AND SENESCENCE reported in cells as different as fibroblasts (11,24,75,78), endothelial cells (57,90), macrophages (5), melanocytes (34), keratinocytes (142), or renal epithelial cells (65). Similarly, the activation of the UPR seems to occur in all types of senescence, whether the inducer is successive replications (7,11,57,75,112), oncogene activation (34,38,142), DNA-damaging agents such as X-rays (90) or adriamycin (38), or oxidative stress (75).…”

Overexpression of nicotinamide N-methyltransferase in gastric cancer tissues and its potential post-translational modification

“…Two-dimensional gel electrophoresis (2-DE) is widely used for in investigation of protein complements between diseased and healthy tissue with the purpose of developing diagnostic markers and detecting novel drug targets (Wilkins et al, 1996;Gygi et al, 2000). Proteomic technologies are providing the tools needed to discover and identify biomarkers associated with diverse diseases and biological processes (Blackstock et al, 1999;Hanash, 2003;Choi et al, 2004;Eun et al, 2004). There have been many studies including analysis of prognostic factors, development of chemotherapeutic agents, and the search for the early detecting molecules, but there are currently very few molecular markers that are clinically in use.…”

Biliverdin reductase A in the prevention of cellular senescence against oxidative stress

“…In addition to replicative senescence, cells can also exhibit stress-induced or premature cellular senescence upon exposure to oxidants, DNA-damaging agents, histone deacetylase inhibitors, or overexpression of certain oncogenes (Chen et al, 1995;Serrano et al, 1997;Robles and Adami, 1998;Zhu et al, 1998;Choi and Kim, 2004). Compared with early-passage cells, senescent HDFs contain higher levels of oxidative DNA lesions (Chen et al, 1995), presenting the possibility that oxidative damage may be responsible for triggering the activation of cell cycle checkpoints in senescent cells.…”