Expression of cystatin C prevents oxidative stress-induced death in PC12 cells

Nishiyama, Keiji; Konishi, Akio; Nishio, Chika; Araki-Yoshida, Kiyomi; Hatanaka, Hiroshi; Kojima, Masami; Ohmiya, Yoshihiro; Yamada, Masashi; Koshimizu, Hisatsugu

doi:10.1016/j.brainresbull.2005.05.020

Cited by 37 publications

(26 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These factors have been shown to be antiapoptotic in cancer cells (15,17), neuroblastoma cells (30), PC-12 cells (21), and endothelial cells (12) but not in isolated cardiomyocytes or in the rat cardiomyocyte-derived cell line H9c2. TIMP-1 is antifibrotic in the heart because of inhibition of MMPs (28).…”

Section: Resultsmentioning

confidence: 99%

Factors released from embryonic stem cells inhibit apoptosis of H9c2 cells

Singla

McDonald²

2007

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Our recent study (Singla DK, Hacker TA, Ma L, Douglas PS, Sullivan R, Lyons GE, Kamp TJ, J Mol Cell Cardiol 40: 195-200, 2006) suggests that transplanted embryonic stem (ES) cells subsequent to myocardial infarction differentiate into the major cell types in the heart and improve cardiac function. However, the extent of regeneration is relatively meager compared with the observed functional improvement. The mechanisms underlying their improved function are completely unknown. In this report, we provide evidence using a cell culture model system for novel mechanisms that involve the release of cytoprotective, antiapoptotic factor(s) from ES cells and inhibit H 2O2-induced apoptosis in the rat cardiomyocyte-derived cell line H9c2. Conditioned medium (CM) from growing mouse ES cells treated with and without H2O2 was generated. Apoptosis was induced after exposure to H2O2 in H9c2 cells for 2 h followed by replacement with fresh cell culture or ES cell-CM. After 24 h, H9c2 cells treated with both ES cell-CMs demonstrated significantly decreased apoptosis, as determined by terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling staining, apoptotic ELISA, caspase-3 activity, and DNA ladder. Next, using Luminex technology, we examined the presence of antiapoptotic proteins cystatin c, osteopontin, and clusterin and anti-fibrotic, tissue inhibitor of metalloproteinase-1 (TIMP-1) in both ES cell-CMs. The levels of released factors were 2-to 170-fold higher than those in H9c2 cell-CM. Antiapoptotic effects of ES cell-CM were significantly inhibited with TIMP-1 antibody, suggesting that TIMP-1 is an important factor to inhibit apoptosis. Furthermore, we used CM from an TIMP-1-overexpressing cell line and demonstrated that H2O2-induced apoptosis in the H9c2 cells was significantly inhibited. These observations demonstrate that factors released from ES cells contain antiapoptotic factors and that the effects are mediated by TIMP-1. Moreover, these findings suggest that released factors might be useful for therapeutic applications in ischemic heart disease as well as for many other diseases. hydrogen peroxide; tissue inhibitor of metalloproteinase-1

show abstract

Section: Resultsmentioning

confidence: 99%

Factors released from embryonic stem cells inhibit apoptosis of H9c2 cells

Singla

McDonald²

2007

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…Cystatin C plays beneficial and pathologic roles in Alzheimer disease (17,(42)(43)(44). The beneficial roles have been attributed to the protease inhibitory function of cystatin C (42), to its largely uncharacterized neuroprotective or neurogenic activities (43,44), or to its capacity to inhibit formation of A␤ amyloid (17).…”

Section: Discussionmentioning

confidence: 99%

Developmental Regulation of Synthesis and Dimerization of the Amyloidogenic Protease Inhibitor Cystatin C in the Hematopoietic System

Xu¹,

Lindemann

Vega-Ramos

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Dimerization of cystatin C initiates formation of amyloid fibrils in vascular walls. Results: Reactive oxygen species regulate cystatin C dimerization in cells of the hematopoietic system, which are major contributors to the total pool of circulating cystatin C. Conclusion: Cystatin C dimerization is regulated in hematopoietic cells. Significance: Cystatin C synthesis and dimerization might be manipulated for therapeutic gain.

show abstract

“…Neither up nor down regulation of cystatin significantly alters levels of apoptosis of these cancer cells in culture. In another cell system, in response to oxidative stress, overexpression of cystatin C protects PC12 cells against apoptosis (Nishiyama et al, 2005). It is believed oxidative damage to lysosomal membranes causes leakage of cathepsins as a trigger for apoptosis in this system.…”

Section: Type II Cystatinsmentioning

confidence: 99%