Hydration and Elevated Calcium Alone Do Not Produce Xylose Nuclear Cataract: Role of Proteolysis by Calpain

Azuma, Mitsuyoshi; David, Larry L.; Shearer, Thomas R.

doi:10.1159/000267138

Cited by 14 publications

(4 citation statements)

References 18 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These caspases also cleave crystalline proteins [27,37]. Most ARCs contain elevated levels of Ca ++ in the lens, and the Ca ++ influx is considered to be due to the activation of Ca ++ dependent proteinases including m-calpain [2,10,36]. On the other hand, our results suggest that the cataractogenic stress induced the UPR which increase the release of Ca ++ from the ER.…”

Section: Discussionmentioning

confidence: 80%

“…Because the UPR releases Ca ++ into the cytoplasm from the ER [41], we hypothesized that m-calpain [2,36] might cleave the Nrf2 protein in the HLECs. To test this, HLECs were treated with 15 mM Hcy with an addition of 1 mM CaCl 2 in DMEM (DMEM contains 1.25 mM of Ca ++ ), and the m-calpain inhibitor, SJA6017, for 24 h. The cleavage of native Nrf2 was not increased to detectable levels after the exposure (data not shown).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Age-related cataracts: Homocysteine coupled endoplasmic reticulum stress and suppression of Nrf2-dependent antioxidant protection

Rajan

Periyasamy

Madson

et al. 2012

Chemico-Biological Interactions

View full text Add to dashboard Cite

To determine whether high levels of homocysteine (Hcy) induce endoplasmic reticulum (ER) stress with suppression of the nuclear factor-erythroid-2-related factor 2 (Nrf2)-dependent antioxidant protection in lens epithelial cells (LECs). ER stress was acutely induced by exposure of LECs to 100 μM Hcy without FCS and also by exposure to 5 mM Hcy with 10% FCS. After exposure to Hcy, significant changes were found in P-PERK, P-eIF2α, XBP1, Nrf2, and Keap1 within 24 h. The production of reactive oxygen species (ROS) was increased after Hcy exposure. The downstream enzymes of Nrf2 like, catalase, and glutathione reductase, were significantly decreased. These results suggested that the Hcy-induced ER stress suppressed the Nrf2-dependent antioxidant protection and simultaneously generated ROS which resulted in further oxidation and death of LECs. The loss of Nrf2 is mainly due to proteosomal degradation and m-calpain activation by the increased levels of cytoplasmic Ca++. The caspases also play a role in the degradation of Nrf2. Our findings demonstrated that high levels of Hcy induce ER stress, chronic UPR, alter the levels of UPR specific proteins, increase the production of ROS, degrade Nrf2 and block the Nrf2-dependent antioxidant defense protection in LECs. Thus, the upregulation of ROS might exceed the Nrf2 dependent antioxidant defense protection in the LECs and result in the highly oxidized lenses and resulted in ARCs.

show abstract

Section: Discussionmentioning

confidence: 80%

Section: Resultsmentioning

confidence: 99%

Age-related cataracts: Homocysteine coupled endoplasmic reticulum stress and suppression of Nrf2-dependent antioxidant protection

Rajan

Periyasamy

Madson

et al. 2012

Chemico-Biological Interactions

View full text Add to dashboard Cite

show abstract

“…One possible candidate for this role is calpain. The calpains are intracellular, calcium-dependent cysteine proteases (28) that have been shown to factor in the formation of nuclear cataracts (29). There are two forms of calpain.…”

Section: Discussionmentioning

confidence: 99%

Cataractogenesis in Transgenic Mice Containing the HIV-1 Protease Linked to the Lens αA-Crystallin Promoter

Tumminia

Jonak

Focht

et al. 1996

Journal of Biological Chemistry

View full text Add to dashboard Cite

Several lines of transgenic mice were generated with either active or inactive forms of the human immunodeficiency virus type 1 (HIV-1) protease gene under the control of the mouse lens alpha A-crystallin promoter. Mice bearing the inactive protease coding sequence displayed no gross abnormalities in the lens, while mice with the active protease developed time-dependent bilateral cataracts. One line, TG61, developed cataracts in utero while the second line, TG72, developed cataracts postnatally. TG61 mice, homozygous for the transgene, developed severe microphthalmia and were significantly smaller than the control mice at postnatal day 30. two-dimensional-polyacrylamide gel electrophoresis analysis of the protein profiles of TG72 and TG61 lenses revealed extensive modifications in the lens crystallins. Proteolysis in the homozygous TG72 mouse lenses began at postnatal day 20 with the disappearance or partial loss of beta B1-, beta B3-, and beta A3-crystallins and the appearance of crystallin fragments. Protein leakage and the gradual breakdown of cytoskeletal elements also occurred. In contrast, the opacification of the homozygous TG61 lenses appeared to have been influenced by differentiation and developmental processes. It appears that HIV-1 protease expression activates other proteases, and these enzymes, in concert with HIV-1 protease, are responsible for the protein modifications that eventually result in the opacification of the lens.

show abstract

“…This suggests that the mechanical stress due to contact with the intraocular lens induces secondary cataract formation. In addition, it has been suggested that accumulation of sugar alcohols in the lens results in cellular swelling and Ca 2+ accumulation in sugar cataracts (Azuma et al . 1992).…”

mentioning

confidence: 99%

Visualization of elementary mechanosensitive Ca²⁺‐influx events, Ca²⁺ spots, in bovine lens epithelial cells

Ohata

Tanaka

Maeyama

et al. 2001

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

Hydration and Elevated Calcium Alone Do Not Produce Xylose Nuclear Cataract: Role of Proteolysis by Calpain

Cited by 14 publications

References 18 publications

Age-related cataracts: Homocysteine coupled endoplasmic reticulum stress and suppression of Nrf2-dependent antioxidant protection

Age-related cataracts: Homocysteine coupled endoplasmic reticulum stress and suppression of Nrf2-dependent antioxidant protection

Cataractogenesis in Transgenic Mice Containing the HIV-1 Protease Linked to the Lens αA-Crystallin Promoter

Visualization of elementary mechanosensitive Ca²⁺‐influx events, Ca²⁺ spots, in bovine lens epithelial cells

Contact Info

Product

Resources

About

Hydration and Elevated Calcium Alone Do Not Produce Xylose Nuclear Cataract: Role of Proteolysis by Calpain

Cited by 14 publications

References 18 publications

Age-related cataracts: Homocysteine coupled endoplasmic reticulum stress and suppression of Nrf2-dependent antioxidant protection

Age-related cataracts: Homocysteine coupled endoplasmic reticulum stress and suppression of Nrf2-dependent antioxidant protection

Cataractogenesis in Transgenic Mice Containing the HIV-1 Protease Linked to the Lens αA-Crystallin Promoter

Visualization of elementary mechanosensitive Ca2+‐influx events, Ca2+ spots, in bovine lens epithelial cells

Contact Info

Product

Resources

About

Visualization of elementary mechanosensitive Ca²⁺‐influx events, Ca²⁺ spots, in bovine lens epithelial cells