Age-related changes of calpain II and α-crystallin in the lens of hereditary cataract (Nakano) mouse

Yoshida, Hideya; Murachi, Takashi; Tsukahara, I

doi:10.3109/02713689509000005

Cited by 29 publications

(22 citation statements)

References 16 publications

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“…The observation that calpain 1, 2, and 3 are expressed in the mouse lens is in agreement with earlier reports (58,59). Calpain 7 (also known as PalBH) has not previously been detected in the lens, but its presence is not unexpected, as calpain 7 mRNA is widely expressed (60).…”

Section: Discussionsupporting

confidence: 94%

Calpain Expression and Activity during Lens Fiber Cell Differentiation

María

Shi

Kumar

et al. 2009

Journal of Biological Chemistry

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In animal models, the dysregulated activity of calcium-activated proteases, calpains, contributes directly to cataract formation. However, the physiological role of calpains in the healthy lens is not well defined. In this study, we examined the expression pattern of calpains in the mouse lens. Real time PCR and Western blotting data indicated that calpain 1, 2, 3, and 7 were expressed in lens fiber cells. Using controlled lysis, depth-dependent expression profiles for each calpain were obtained. These indicated that, unlike calpain 1, 2, and 7, which were most abundant in cells near the lens surface, calpain 3 expression was strongest in the deep cortical region of the lens. We detected calpain activities in vitro and showed that calpains were active in vivo by microinjecting fluorogenic calpain substrates into cortical fiber cells. To identify endogenous calpain substrates, membrane/cytoskeleton preparations were treated with recombinant calpain, and cleaved products were identified by twodimensional difference electrophoresis/mass spectrometry. Among the calpain substrates identified by this approach was ␣II-spectrin. An antibody that specifically recognized calpaincleaved spectrin was used to demonstrate that spectrin is cleaved in vivo, late in fiber cell differentiation, at or about the time that lens organelles are degraded. The generation of the calpain-specific spectrin cleavage product was not observed in lens tissue from calpain 3-null mice, indicating that calpain 3 is uniquely activated during lens fiber differentiation. Our data suggest a role for calpains in the remodeling of the membrane cytoskeleton that occurs with fiber cell maturation.

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Section: Discussionsupporting

confidence: 94%

Calpain Expression and Activity during Lens Fiber Cell Differentiation

María

Shi

Kumar

et al. 2009

Journal of Biological Chemistry

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“…Calpain would be a logical candidate for the activated cysteine protease activity in the TG 72 lens. Two classes of Ca 2ϩ -dependent cysteine proteases, calpain I (-calpain) and calpain II (m-calpain), and the endogenous inhibitor polypeptide calpastatin are found in the mammalian lens (34). Calpain II is the more abundant form in the lens compared with calpain I.…”

Section: Resultsmentioning

confidence: 99%

Cysteine Protease Activated by Expression of HIV-1 Protease in Transgenic Mice

Mitton

Kamiya

Tumminia

et al. 1996

Journal of Biological Chemistry

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Transgenic mice, homozygous for HIV-1 protease expression in the eye lens, display degradation of some lens crystallins and cytoskeletal proteins prior to cataract formation on postnatal days 23-25. Alterations to the internal lens hydration state also occur; therefore, the status of the aquaporin protein MIP26 was examined over postnatal days 16 -25 to determine if it was altered during cataractogenesis. The MIP was identical in transgenic and control lenses until day 21. By postnatal day 25 (frank cataract), in the lenses obtained from transgenic animals, the 26-kDa band was absent and there was a concurrent increase in the proportion of MIP23. Immunoblotting demonstrated cleavage at the C terminus. Lenses were also maintained in an organ culture system to demonstrate that the cataractogenic process is inherent to the isolated lens and to determine the contribution of cysteine protease action. Organ culture experiments revealed a similar progression to nuclear cataract formation as seen in vivo. Two-dimensional gel analysis of the soluble lens crystallin fraction of organ cultured lenses revealed the same cleavage pattern as occurs in vivo. Organ culture of transgenic lenses with E64, a cysteine protease inhibitor, dramatically delayed cataractogenesis and prevented proteolytic cleavage of both MIP26 and crystallins. HIV-1 protease, while the trigger of cataract formation, does not appear to be the protease responsible for cleavage of MIP or lens crystallins. These results suggest that activation of endogenous cysteine protease activity is involved in the cleavage of these proteins and occurs downstream of HIV-1 protease action.

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“…γ-Crystallin (10) did not act as a substrate. In contrast, lens actin, vimentin and spectrin/fodrin (10,15,17) appear to be substrates for calpain.…”

mentioning

confidence: 99%

“…Slight variation in calcium concentration is sufficient to modulate the proteolytic activity of calpain, or autolysis of calpain, or even its interaction with endogenous inhibitor protein (calpastatin/calpain) (13,14). In the lens, calpain is mostly found either in epithelial cells or cortex cytosol (11,15).…”

mentioning

confidence: 99%

Modelling cortical cataractogenesis XXIX. Calpain proteolysis of lens fodrin in cataract

Kilic

Trevithick

1998

IUBMB Life

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SUMMARYThe relation between cataract and calpain proteolysis of lens fodrin was studied in two systems: elevated glucose (55.6 mM, diabetic model), and cytochalasin D (CD, 10 2 mM, actin depolymerization-induced opacity model). Glucose treatment (48 h) caused a visible opaque layer and enzyme leakage, with a concomitant accumulation of ([Ca2+]¡) around the lens equatorial cortex. CD caused both earlier and greater opacity and enzyme leakage than glucose. Lens fodrin digestion occurred in parallel with the timing and extent of calcium elevation. A calpain inhibitor peptide (CIP, 10" 2 mM) reduced the proteolysis of fodrin, opacity, and enzyme leakage in glucose-treated lenses but only partially retarded them in CDtreated lenses. These results suggest a mechanism in which calpain proteolysis of fodrin is a critical event in lens damage during opacification of cortical cataract.

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Age-related changes of calpain II and α-crystallin in the lens of hereditary cataract (Nakano) mouse

Cited by 29 publications

References 16 publications

Calpain Expression and Activity during Lens Fiber Cell Differentiation

Calpain Expression and Activity during Lens Fiber Cell Differentiation

Cysteine Protease Activated by Expression of HIV-1 Protease in Transgenic Mice

Modelling cortical cataractogenesis XXIX. Calpain proteolysis of lens fodrin in cataract

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