Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mesangial cell (MC) hyperplasia and accumulation of extracellular matrix are the predominant features of HIV-associated nephropathy (HIVAN). Since mice transgenic for HIV-1 genes show renal lesions mimicking HIVAN, we studied the effect of HIV-1 gp160 protein on cultured murine MC (MMC) proliferation and apoptosis. HIV-1 gp160 protein stimulated (p < 0.001) MMC proliferation when compared with control MMCs. This effect of gp160 protein peaked at a concentration of 0.01 microg/ml. MMCs treated with a higher concentration of gp160 protein (0.1 microg/ml) or for a prolonged period of time (72 h) showed apoptosis rather than cell proliferation. These studies were further confirmed by DNA fragmentation and end labeling assays. gp160 also enhanced apoptosis in human MCs. Tumor necrosis factor (TNF)-alpha enhanced (p < 0.001) MMC apoptosis, and anti-TNF-alpha antibodies inhibited gp160-induced MMC apoptosis. In addition, gp160 protein attenuated MMC expression of Bcl-2 mRNA expression. These results suggest that gp160-induced apoptosis may be affected in part by the release of TNF-alpha and associated with attenuated mRNA expression of Bcl-2 by MMCs.
Nephron 1997
PMID:HIV-1 gp160 envelope protein modulates proliferation and apoptosis in mesangial cells. 922 28

To understand the expression of inducible nitric oxide synthase (iNOS) and its possible association with apoptosis in human lupus nephritis, 48 renal tissue samples from patients with lupus nephritis were investigated immunohistochemically and by the terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling method for the detection of iNOS and apoptosis, respectively. Modulation of apoptosis by p53 and Bcl-2 was also evaluated. This study showed immunohistochemical evidence of iNOS expression, predominantly in the glomerular and tubulointerstitial cells of class-IV lupus nephritis. The frequency of iNOS+ glomeruli was significantly correlated with that of apoptosis+ glomeruli, and the frequency of the latter was also significantly correlated with that of the glomeruli showing p53 overexpression. Bcl-2 was predominantly expressed in the cellular and fibrocellular crescents. This study suggests that induction of iNOS, and thus nitric oxide production, plays a role in the occurrence of apoptosis in the glomeruli of lupus nephritis; and the occurrence of apoptosis might in part be modulated by p53 and Bcl-2-related pathways. The expression of Bcl-2 in predominantly cellular and fibrocellular crescents suggests that Bcl-2 may participate in persistent proliferation of the crescentic cells.
Nephron 1997
PMID:Expression of inducible nitric oxide synthase and apoptosis in human lupus nephritis. 943 61

Cell-matrix interactions have major effects upon phenotypic features such as gene regulation, cytoskeletal structure, differentiation and aspects of cell growth control. Detachment from the matrix epithelial cells induces programmed cell death, and this cell detachment induced apoptosis has been referred to as 'anoikis'. This study was undertaken to determine whether apoptosis is induced by inhibition of contact with extracellular matrix (ECM) in collecting duct cells and to investigate the signaling mechanisms of the process. Upon detachment from ECM, mouse inner medullary collecting duct cells (mIMCD-3) and mouse outer cortical collecting duct cells (M-1), which were derived from an SV40 transgenic mouse, entered into programmed cell death. Forced suspension of mIMCD-3 or M-1 cells did not affect the expression of Bcl-2-related proteins and did not activate c-Jun NH(2)-terminal kinase. Detachment of cells from ECM activated p38 mitogen-activated protein kinase (p38), but its inhibition with SB203580 did not protect cells from anoikis. Detachment of cells from matrix inhibited NF-kappaB activity, and the inhibition of NF-kappaB activity by overexpression of nonphosphorylatable I-kappaB increased detachment-induced apoptotic cell death in M-1 cells. Forced suspension of M-1 cells still activated p53 activity. Caspase-8 was activated during anoikis, but the time course of its activation was in accordance with DNA fragmentation. These results indicate that detachment from ECM induces apoptosis in the kidney collecting duct cells. Changes in expression levels of Bcl-2-related proteins or activation of JNK/p38 kinase are not critical for anoikis. Decrease in NF-kappaB activity and activation of p53 induced by inhibition of interaction with ECM play roles in anoikis in SV-40-transformed collecting duct cells. Caspase-8 is activated during detachment-induced apoptosis, the mechanisms of which are independent of activation of cell death receptors.
Nephron 1999
PMID:Apoptosis induced by inhibition of contact with extracellular matrix in mouse collecting duct cells. 1057 96

Congenital obstructive nephropathy is a common disease affecting fetuses and young children. The kidney shows profound morphologic and functional changes. The physiologic developmental kidney program is disturbed in the most advanced cases, arguing for altered temporal/spatial expression of genes which control normal nephrogenesis. Major regulators of mesenchymal-epithelial transformation and collecting duct and tubular development such as WT1 and Sall1 are decreased with obstruction. Additional candidate genes include GDNF/cRET, LIM1 and Pax2. Excessive apoptosis is an undisputed mechanism in these processes, mediated by decreased expression of apoptosis inhibiting genes (Bcl-2, HGF, IGF, BMP7), and overexpression of pro-apoptotic genes like Bax and TGF-beta. Renin and AT2R implicated in renal vascular development are decreased. Numerous extracellular matrix genes including Matrilysin are altered. The emerging theories of the biology of congenital obstructive nephropathy suggest new targets for therapeutic interventions with profound implications for these children.
Nephron Exp Nephrol 2003
PMID:Biology of congenital obstructive nephropathy. 1266 Apr 11