Biomedical subjects

Stefan David

Publications and source records attributed to Stefan David.

3 recordsLinked to original sources

PubMed2006

The complement system in central nervous system diseases.

The activation of complement system is important factor in inflammatory, neurodegenerative and cerebrovascular diseases. CNS cells are able to synthesize complement components, and myelin and oligodendrocytes (OLG) are known to activate the classical pathway of complement in vitro in the absence of antibodies. Although activation of the complement system is known to promote tissue injury, recent evidence has also indicated that this process can have neuroprotective effects. In particular, terminal C5b-9 complexes enhance OLG survival both in vitro and in vivo. Complement activation may also reduce the accumulation of amyloid and degenerating neurons by promoting their clearance and suggest that certain inflammatory defense mechanisms in the brain may be beneficial in neurodegenerative disease. Complement system activation plays also an important role in brain damage after ischemic injury or head trauma. These findings strongly suggest that complement activation and membrane assembly of C5b-9 can play a role in injury but can also provide neuroprotection depending on the pathophysiological context.

Animals↗

PubMed2006

JNK1 activation mediates C5b-9-induced P0 mRNA instability and P0 gene expression in Schwann cells.

The protein zero (P0) glycoprotein is an important component of compact peripheral nerve myelin produced by the glial cells of the mammalian peripheral nervous system. P0 mRNA expression is reduced following exposure of Schwann cells to sublytic C5b-9, the terminal activation complex of the complement cascade. Sublytic complement treatment decreased P0 mRNA by 81% within 6 h and required C5b-9 assembly. C5b-9 induced a threefold increase in both JNK1 activity and c-jun mRNA within 20 and 30 min, respectively, compared with cells treated with either human serum depleted of complement component C7 (C7dHS) or medium alone. Sublytic C5b-9 stimulation, in the presence of the transcription inhibitor Actinomycin D, decreased P0 mRNA expression by 52%, indicating that mRNA was selectively destabilized. This effect was prevented by pretreatment with L-JNK inhibitor 1 (L-JNKI1). To study a potential inhibition of P0 gene transcription, we transfected Schwann cells with a P0 promoter-firefly luciferase construct. Sublytic C5b-9 stimulation of the transfected cells decreased luciferase activity by 82% at 6 h, and this effect was prevented by pretreatment with L-JNKI1 inhibitor. Our results indicate that the ability of C5b-9 in vitro to affect P0 gene expression is mediated via JNK1 activation that leads to enhanced mRNA decay and transcriptional repression of P0.

Animals↗

PubMed2005

Overexpression of RGC-32 in colon cancer and other tumors.

Tumors often exhibit deregulation of the cell cycle and overexpression of cyclins and cyclin-dependent kinases (CDKs). Response gene to complement (RGC)-32 is a substrate and regulator of CDC2 and its overexpression induces cell cycle activation. We investigated RGC-32 mRNA and protein expression in tumors with special emphasis in colon carcinoma. By using an expression array technique we found that 19% of tumor tissues showed increased RGC-32 mRNA expression over the levels of corresponding normal tissues. On the other hand, an increased RGC-32 protein was found in 70% of colon adenocarcinoma samples tested. In colon carcinomas, two major patterns of RGC-32 immunoreactivity were seen: staining of malignant epithelial cells only in some tumors and RGC-32 reactivity of both malignant epithelia as well as cells in the interstitium in others. Colonic epithelium obtained from normal individuals was consistently negative for RGC-32 protein. Overexpression of RGC-32 protein was found in other tumors including prostate, bladder, breast, lung, and other digestive tract tumors. RGC-32 expression was present in the same malignant epithelial cells that also expressed the proliferation marker Ki-67. Our data suggest that RGC-32 overexpression might be part of the deregulation of the cell cycle that is required for the growth of tumor cells.

Adenocarcinoma↗