Intracellular glutathione influences collagen generation by mesangial cells.

Abstract:

:The cellular redox state is altered in a number of pathological conditions, including various forms of glomerular injury and diabetes. For example, glucose, via the pentose phosphate pathway generates NADPH, which maintains glutathione (GSH) (part of a major intracellular reducing system) in its reduced state. GSH in turn influences the activity of transcription factors on gene expression. We therefore examined whether changes in cellular GSH influence total collagen synthesis and mRNA levels for collagen I, collagen IV and TGF-beta in SV-40 transformed mouse mesangial cells (MC) maintained in either 5 or 25 mM glucose media. Total intracellular GSH was increased by N-acetylcysteine (NAC; 10 mM) or decreased with the GSH synthesis inhibitor buthionine sulfoximine (BSO; 0.2 mM) in MC. NAC increased 3H-proline incorporation into collagenase-sensitive protein while BSO decreased it under both glucose conditions. The presence of BSO did not reverse the increased collagen synthesis seen in the NAC stimulated cells. Northern blot analysis showed increased mRNA levels for collagen I, collagen IV and TGF-beta in cells grown in high glucose (25 mM). NAC increased the mRNA for all three compounds while BSO alone had no effect on these mRNA levels. However, BSO reversed the increased mRNA levels for collagen I, IV and TGF-beta seen in the presence of NAC. These findings suggest that the cellular redox state may influence gene transcription in MC, and may have implications in explaining injury-associated alterations of mesangial matrix generation.

journal_name

Kidney Int

journal_title

Kidney international

authors

Shan Z,Tan D,Satriano J,Silbiger S,Schlondorff D

doi

10.1038/ki.1994.286

subject

Has Abstract

pub_date

1994-08-01 00:00:00

pages

388-95

issue

2

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)58567-0

journal_volume

46

pub_type

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