Faculty Opinions recommendation of The immunosuppressive drug mizoribine directly prevents podocyte injury in puromycin aminonucleoside nephrosis.

Cathepsin L, a lysosomal cysteine proteinase, may have a key role in various biological and disease processes by intracellular and extracellular degradation of proteins. We examined the levels of cathepsin L and its intrinsic inhibitors in glomeruli of rats with puromycin aminonucleoside (PAN) nephrosis. In contrast to the weak levels of cathepsin L in normal glomeruli, on days 4 and 8, strong immunostaining was detected in almost all podocytes when proteinuria and pathological changes of the podocytes developed. Cathepsin L was reduced after day 28, but remained in a focal and segmental manner. Cystatin β, an intracellular inhibitor, was not detected in podocytes. However, cystatin C, an extracellular inhibitor, was detected in podocytes after day 4, coincident with cathepsin L. Cystatin C levels were gradually reduced but sustained in many podocytes on day 28, while cystatin C was not detected in podocytes sustained cathepsin L. These results demonstrated that cathepsin L levels are not always accompanied by the levels of its inhibitors in podocytes of PAN nephrosis, suggesting a potential role of cathepsin L in podocyte injury, which is a critical process for the development and progression of tuft adhesion and sclerosis.

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Novel expression of sodium/myo-inositol co-transporter in podocytes in puromycin aminonucleoside nephrosis

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfh026 ◽

2004 ◽

Vol 19 (4) ◽

pp. 817-822 ◽

Cited By ~ 3

Author(s):

Y. Watanabe ◽

T. Kobayashi ◽

E. Yaoita ◽

H. Kawachi ◽

A. Yamauchi ◽

...

Keyword(s):

Puromycin Aminonucleoside ◽

Aminonucleoside Nephrosis ◽

Puromycin Aminonucleoside Nephrosis

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Glomerular Expression of Smooth-Muscle Myosin Heavy-Chain Isoforms in Aminonucleoside Nephrosis in Rats

Clinical Science ◽

10.1042/cs0890045 ◽

1995 ◽

Vol 89 (1) ◽

pp. 45-52 ◽

Cited By ~ 4

Author(s):

Tsukasa Nakamura ◽

Kenjiro Kimura ◽

Isao Ebihara ◽

Toshimasa Takahashi ◽

Yasuhiko Tomino ◽

...

Keyword(s):

Smooth Muscle ◽

Myosin Heavy Chain ◽

Heavy Chain ◽

Proliferating Cell Nuclear Antigen ◽

Smooth Muscle Actin ◽

Nuclear Antigen ◽

Puromycin Aminonucleoside ◽

Proliferating Cell ◽

Aminonucleoside Nephrosis ◽

Puromycin Aminonucleoside Nephrosis

1. We investigated the glomerular expression of three types of myosin heavy-chain isoforms, including S-myosin heavy-chain 40 (SM1), S-myosin heavy-chain 29 (SM2) and FS-myosin heavy-chain 34 (SMemb) in puromycin aminonucleoside nephrosis. 2. There was little change in SM1 and SM2 mRNA levels throughout the experiment. In contrast, glomerular SMemb mRNA increased on days 2 and 4 (before and soon after the onset of proteinuria, respectively), but declined on day 8 (the peak of proteinuria). 3. Histological myosin heavy-chain expression was examined using three antibodies against SM1, SM2 and SMemb. Immunohistochemically, SM1 and SM2 were absent in the glomeruli associated with puromycin aminonucleoside nephrosis until day 20. The SMemb isoform was barely detectable in normal glomeruli, but substantial amounts of SMemb were demonstrated in the glomeruli of rats with puromycin aminonucleoside nephrosis. In the puromycin aminonucleoside-treated rats, the number of SMemb-positive glomerular cells increased on days 2 and 4. 4. We examined whether levels of α-smooth-muscle actin or proliferating cell nuclear antigen correlated with myosin heavy-chain levels in the glomeruli of rats with puromycin aminonucleoside nephrosis. None of the cellular components in the glomeruli was positive for either α-smooth-muscle actin or proliferating cell nuclear antigen in puromycin aminonucleoside nephrosis. 5. Administration of methylprednisolone to puromycin aminonucleoside-treated rats resulted in the rapid disappearance of proteinuria. However, methylprednisolone did not affect SMemb mRNA or immunostaining in the glomeruli of rats with puromycin aminonucleoside nephrosis. 6. These data suggest that SMemb may be a molecular marker for phenotypic change in early glomerular injury, and demonstrate that SMemb regulation differs from that of SM1, SM2, α-smooth-muscle actin and proliferating cell nuclear antigen in the glomeruli of rats with puromycin aminonucleoside nephrosis.

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