RGD Reference Report - A shift in the Bax/Bcl-2 balance may activate caspase-3 and modulate apoptosis in experimental glomerulonephritis. - Rat Genome Database

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A shift in the Bax/Bcl-2 balance may activate caspase-3 and modulate apoptosis in experimental glomerulonephritis.

Authors: Yang, B  Johnson, TS  Thomas, GL  Watson, PF  Wagner, B  Furness, PN  El Nahas, AM 
Citation: Yang B, etal., Kidney Int. 2002 Oct;62(4):1301-13.
RGD ID: 1579984
Pubmed: PMID:12234300   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1523-1755.2002.kid587.x   (Journal Full-text)

BACKGROUND: Although apoptosis has been linked to the renal cell deletion and ensuing renal fibrosis, its regulating mechanisms remain obscure. Of the known regulators of apoptosis, the best characterized is the Bax to Bcl-2 ratio. However, its importance in controlling apoptosis in glomerulonephritis is unclear. Here, using the nephrotoxic nephritis (NTN) model, we evaluated Bax/Bcl-2 in relation to changes in the apoptosis co-ordination enzyme, caspase-3. METHODS: Kidneys were harvested at days 7, 15, 30 and 45 post-injection of anti-glomerular basement membrane antibody into Wistar Kyoto rats. These were analyzed for apoptosis (in situ end labeling of fragmented DNA, light and electron microscopy), Bax/Bcl-2 protein (Western blotting), mRNA (Northern blotting) and distribution (immunohistochemistry), as well as caspase-3 activity (substrate cleavage assay), inflammation (ED1 staining), proliferation (proliferating cell nuclear antigen staining) and fibrosis (Masson's Trichrome staining). RESULTS: Bax mRNA was significantly increased while that of Bcl-2 was decreased throughout the time course (+265% and -62% by day 45). Increased Bax and decreased Bcl-2 protein were noted, significantly so on day 7 (+177% and -21%) and day 45 (+363% and -17%). Bax protein was observed in dilated and atrophic tubules, sclerotic glomeruli and inflamed interstitium, while Bcl-2 was only visible in atrophic tubules. The ratios of Bax to Bcl-2 mRNA and protein were significantly increased at all time points. These correlated (P < 0.05) with up-regulated caspase-3 activity (r = 0.742 and 0.531), apoptosis (r = 0.712 and 0.540), proliferation (r = 0.611, mRNA only), inflammation (ED1+, r = 0.474 and 0.419) and fibrosis (r = 0.474 and 0.729). CONCLUSIONS: Our findings suggest that the changes in the ratio of Bax to Bcl-2 may contribute to the caspase-3 activation and the modulation of renal apoptosis associated with renal inflammation, tubular atrophy and renal fibrosis in experimental glomerulonephritis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
anti-basement membrane glomerulonephritis  ISOBax (Rattus norvegicus)1579984; 1579984mRNA and protein:increased expression:kidneyRGD 
anti-basement membrane glomerulonephritis  ISOBcl2 (Rattus norvegicus)1579984; 1579984mRNA and protein:decreased expression:kidneyRGD 
anti-basement membrane glomerulonephritis  IEP 1579984mRNA and protein:increased expression:kidneyRGD 
anti-basement membrane glomerulonephritis  IEP 1579984mRNA and protein:decreased expression:kidneyRGD 

Objects Annotated

Genes (Rattus norvegicus)
Bax  (BCL2 associated X, apoptosis regulator)
Bcl2  (BCL2, apoptosis regulator)

Genes (Mus musculus)
Bax  (BCL2-associated X protein)
Bcl2  (B cell leukemia/lymphoma 2)

Genes (Homo sapiens)
BAX  (BCL2 associated X, apoptosis regulator)
BCL2  (BCL2 apoptosis regulator)


Additional Information