Diabetic State-Induced Activation of Calcium-Activated Neutral Proteinase in Mouse Skeletal Muscle.

Kobayashi, Shogo; Fujihara, Mitsuhiro; Hoshino, Nobuo; Kimura, Ikuko; Kimura, Masayasu

doi:10.1507/endocrj1954.36.833

Cited by 12 publications

(6 citation statements)

References 34 publications

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“…The activation of calpain in diabetic in vivo models in mice 31 and rats [32][33][34] has been reported before with additional findings that high glucose-induced calpain activation reduces endothelial nitric oxide synthase function in mesenteric postcapillary venules, 33 and promotes cataractogenesis in the spontaneous diabetic WBN/Kob rat. 32 This study illustrates a likely close association between the initial rise in [Ca 2 þ ] i in less than 1 h (Figure 3b), the activation of calpain after 2 h (Figure 3a), which leads to a previously unrecognized early cytotoxic injury within 3 h, which is sustained for 24 h (Figure 4a).…”

Section: Discussionsupporting

confidence: 61%

High glucose initiates calpain-induced necrosis before apoptosis in LLC-PK1 cells

Harwood

Allen

Raftery

et al. 2007

Kidney International

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Cells exposed to high ambient glucose concentrations are subject to increases in intracellular calcium ([Ca(2+)](i)). We therefore considered it likely that the calcium-dependent cysteine protease calpain would play a role in the development of high glucose-induced cell injury. After 3 and 24 h, high glucose concentrations (25 mM D-glucose) produced almost identical increases in the degree of necrotic cell death in kidney proximal tubular epithelial cells (LLC-PK(1)) compared to cells treated with control glucose (5 mM D-glucose). Necrotic cell death could be restricted by inhibiting the activity of calpain. High glucose-treated LLC-PK(1) cells were found to have significantly elevated [Ca(2+)](i) concentrations within 1 h, and elevated calpain activity within 2 h compared to control treated cells. The DNA nick sensor poly(ADP-ribose) polymerase (PARP) has previously been shown to be an important driver of high glucose-induced cell death, but here we found that although PARP activity was increased after 24 h, it was unaltered after 3 h. Furthermore, PARP inhibition with PJ-34 did not restrict early high glucose-induced necrosis. Using a gene knockdown strategy with small interference RNA, we found that silencing calpain was effective in reducing the degree of early high glucose-induced necrosis. We conclude that high glucose concentrations evoke an early, calpain-mediated necrosis in cultured proximal tubular cells that is PARP-independent, and precedes the previously recognized activation of apoptosis.

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Section: Discussionsupporting

confidence: 61%

High glucose initiates calpain-induced necrosis before apoptosis in LLC-PK1 cells

Harwood

Allen

Raftery

et al. 2007

Kidney International

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“…The higher Ca content in the diabetic muscle may probably be due to increasing intracellular Ca pools. This possibility is also indicated by some studies showing that intracellular Ca binding protein is increased in the muscle of diabetic mice (Morley et al, 1982), and that calcium-activated neutral protease is activated in the diabetic mouse skeletal muscle (Brooks et al, 1983;Kobayashi et al, 1989). The Mg content in these muscles is also influenced by the diabetic state.…”

Section: Resultsmentioning

confidence: 87%

Diabetic State-Induced Modification of Ca, Mg, Fe and Zn Content of Skeletal, Cardiac and Smooth Muscles.

et al. 1989

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The metal content of diaphragm, gastrocnemius, ventricle, and bladder muscles in genetically obese diabetic KK-CAY and alloxan-diabetic ddY mice was compared with that in prediabetic KK-CAy and normal ddY mice, because the muscles of the diabetic KK-CAY mice had morphological abnormalities, such as atrophy, disappearance of Z-band, disturbed myofibrils and swollen sarcoplasmic reticulum.The amounts of calcium (Ca) in gastrocnemius, ventricle and bladder muscles from the prediabetic KK-CAY mice were significantly 7.7, 98.3, and 36.9% greater, respectively, than those in normal ddY mice. In contrast, the magnesium (Mg) content of the diaphragm, the gastrocnemius, and the ventricle in the prediabetic mice was 8.6, 7.4, and 4.3% lower, respectively, than in the ddY mice. The iron (Fe) content of the diaphragm, gastrocnemius, and ventricle muscles in the prediabetic mice was 29.2, 43.6, and 44.6% greater, respectively, than in the ddY mice. The Ca content in the gastrocnemius muscles of the diabetic KK-CAy mice and the alloxan-diabetic mice was 19.8 and 11.7% higher, respectively, than in the prediabetic and normal mice. The Ca content of the ventricle muscle was increased only in the alloxan-mice. The gastrocnemius Mg was also 9.0 and 5.5% greater in the KK-CAY and the alloxan-mice. The Fe content of the diaphragm and the gastrocnemius muscles from the KK-CAY mice was 27.3 and 23.2% greater, respectively, than in the prediabetic mice. The zinc (Zn) content of the gastrocnemius and the bladder was 16.4 and 18.0% higher, but the ventricle Zn was 13.4% lower, respectively, than in the prediabetic control. The changes in metal content induced by the diabetic state may be related to the morphological abnormalities.

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“…Taken together, these studies suggest that calpains play a role in inflammatory processes of the cardiovascular system. Interestingly, increased calpain activity has been described in non-vascular diabetic tissues, such as skeletal muscle (33) and platelets (34). Furthermore, mutation of the gene-encoding calpain 10 (CAPN10) has recently been associated with an increased prevalence of Type II diabetes in humans (35), highlighting the importance of calpains in the regulation of fundamental signaling pathways in diabetes.…”

Section: Discussionmentioning

confidence: 99%

A novel role for calpains in the endothelial dysfunction of hyperglycemia

2003

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Recent studies have reported that the activity of the calcium-dependent protease calpain is increased in acute inflammatory processes of the cardiovascular system. Because diabetes is associated with vascular inflammation, we hypothesized that increased calpain activity in response to hyperglycemia may play a role in diabetic cardiovascular disease. The effects of calpain inhibition on leukocyte-endothelium interactions induced by hyperglycemia were examined by intravital microscopy. Intraperitoneal administration of the selective calpain inhibitor benzyloxycarbonyl-leucyl-leucinal (5 micromol/L) prevented the up-regulation of leukocyte-endothelium interactions in response to 25 mmol/L D-glucose via a nitric oxide-dependent mechanism. Furthermore, treatment of rats with D-glucose significantly decreased basal endothelial NO release in mesenteric post-capillary venules, a phenomenon prevented by inhibition of calpain activity. Immunoprecipitation studies revealed that glucose induces loss of NO via a calpain-dependent decrease in the association of hsp90 with endothelial nitric oxide synthase. In addition, inhibition of calpain activity decreased endothelial cell surface expression of the pro-inflammatory adhesion molecules ICAM-1 and VCAM-1 during hyperglycemia. These data demonstrate that calpains contribute to important inflammatory events during hyperglycemia and that pharmacological inhibition of calpain activity attenuates leukocyte-endothelium interactions and preserves eNOS function.

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Diabetic State-Induced Activation of Calcium-Activated Neutral Proteinase in Mouse Skeletal Muscle.

Cited by 12 publications

References 34 publications

High glucose initiates calpain-induced necrosis before apoptosis in LLC-PK1 cells

High glucose initiates calpain-induced necrosis before apoptosis in LLC-PK1 cells

Diabetic State-Induced Modification of Ca, Mg, Fe and Zn Content of Skeletal, Cardiac and Smooth Muscles.

A novel role for calpains in the endothelial dysfunction of hyperglycemia

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