Calpain cleaves methionine aminopeptidase-2 in a rat model of ischemia/reperfusion

Clinkinbeard, Tiffanie; Ghoshal, Sakti Prasad; Craddock, Susan D.; Pettigrew, L. Creed; Guttmann, Rodney P.

doi:10.1016/j.brainres.2012.12.039

Cited by 15 publications

(11 citation statements)

References 42 publications

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“…Recently, Clinkinbeard et. al., reported that human p67 also has auto-proteolysis activity that generates p52 segment of this protein and this activity is further augmented by a metalloproteinase, calpain (12). We therefore believe that the faster migrating proteins like p52 and p26 are the cleavage products of full-length p67, which may have originated from ~2.2 kb transcript whereas, ~60 kDa protein may coming from the translation of ~1.4 kb transcript from mice.…”

Section: Fig4 Immunoblot Analysis Of Mouse P67 In Multiple Tissues Fmentioning

confidence: 95%

Analysis of P67 Expression in Different Mouse Tissues

2016

International Journal of Advanced Research in Chemical Science

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A ~1.9kb cDNA containing the entire coding region, 5' UTR, and 3' UTR is cloned from rat tumor hepatoma (KRC-7) cells. It was further characterized for protein expression in rabbit reticulocyte lysates. Later, this cDNA was used for extensive mutagenesis and biochemical studies to identify specific domains/sites of rat p67 that are essential for its functions. To investigate whether similar size transcript is also present in mouse tissues, we examined the tissue distributions of mouse p67 transcript and protein from male and female mice. We found that there are two mouse p67 transcriptsone is ~1.4kb long whereas the other is ~2.2 kb long. The ~1.4 kb long transcript is present in almost all tissues tested whereas the ~2.2 kb transcript is present in brain, spleen, skeletal muscle, and possibly in lungs. Our analysis for the tissue distributions of p67 protein detected several proteins corresponding to ~67 kDa, ~60 kDa, 52 kDa, 26 kDa, and possibly others in different proportions in various tissues of both male and female mice. Keywords: mouse p67 gene, tissue distribution of mouse p67 transcript, tissue distribution of p67 in both male and female mice Abbreviations used kb, kilobase pairs; p67, a 67 kDa glycoprotein that binds to both eukaryotic initiation factor 2 (eIF2) and extracellular signal-regulated kinases 1 & 2 (ERK1/2); p52, the downstream 108-480 segment of p67; and p26, the N-terminal 1-107 amino acid segment of p67.

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Section: Fig4 Immunoblot Analysis Of Mouse P67 In Multiple Tissues Fmentioning

confidence: 95%

Analysis of P67 Expression in Different Mouse Tissues

2016

International Journal of Advanced Research in Chemical Science

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“…By using pharmacological inhibitors or mice deficient in calpain-1 or calpain-2 or mice over-expressing calpastatin, the endogenous inhibitor, many studies demonstrated that inactivation of calpain inhibited the atherosclerosis, suggesting that calpains gets involved in the pathogenesis of atherosclerosis (Clinkinbeard et al 2013;Hua and Nair 2015;Miyazaki et al 2013;Ruetten and Thiemermann 1997;Takeshita et al 2013). …”

Section: Discussionmentioning

confidence: 99%

“…Among the superfamily, Calpain-1 and calpain-2 are categorized as "conventional calpain" (Daugherty et al 2000). By using pharmacological inhibitors or mice deficient in calpain-1 or calpain-2 or mice over-expressing calpastatin, the endogenous inhibitor, many studies demonstrated that inactivation of calpain inhibited atherosclerosis, suggesting the involvement of calpains in the development of atherosclerosis (Clinkinbeard et al 2013;Hua and Nair 2015;Miyazaki et al 2013;Ruetten and Thiemermann 1997;Takeshita et al 2013). We previously reported that calpain-1 gets involved in the atherogenesis by up-regulating the scavenger receptor CD36 expression (Yang et al 2016).…”

Section: Introductionmentioning

confidence: 99%

Calpain inhibitor I attenuates atherosclerosis and inflammation in atherosclerotic rats through eNOS/NO/NF-κB pathway

Yin

Yang³

et al. 2018

Can. J. Physiol. Pharmacol.

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We previously reported that calpain, the Ca2+-sensitive cysteine protease, gets involved in atherogenesis. This study aimed to investigate the effects of calpain inhibitor I (CAI, 5 mg/kg per day) with or without NG-nitro-l-arginine-methyl ester (l-NAME) (100 mg/kg per day), the inhibitor of nitric oxide synthase (NOS), on atherosclerosis and inflammation in a rat model induced by high-cholesterol diet (HCD). The results demonstrated HCD increased protein expression of calpain-1 but not calpain-2 in aortic tissue. In addition, CAI reduced the thickness of atherosclerotic intima compared with HCD group, which was weakened by the l-NAME combination. CAI with or without l-NAME decreased the activity of calpain in the aorta. Also, CAI decreased the expressions of vascular cell adhesion molecule-1 (VCAM-1), intracellular cell adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1) in the aorta at the levels of both mRNA and protein. Furthermore, CAI increased the activity and the protein expression of endothelial NOS (eNOS) accompanied by increased content of NO and downregulated the protein expression of nuclear factor κB (NF-κB) of the nucleus in the aorta. However, the abovementioned effects were at least partly cancelled by l-NAME except for the protein expression of eNOS. The results suggested that CAI attenuated atherosclerosis and inflammation through eNOS/NO/NF-κB pathway.

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“…Calpains recognize various intracellular substrate molecules, thereby controlling cellular activities. Numerous in vivo and in vitro experiments employing genetic and pharmacological approaches have focused on the roles of calpains in cardiovascular diseases [ 19 – 23 ]. Calpain-1 was increased in calcified aortic wall of rats with ageing at levels of transcripts, protein, and activity [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Calpain-1 Mediated Disorder of Pyrophosphate Metabolism Contributes to Vascular Calcification Induced by oxLDL

et al. 2015

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We previously reported that oxidized low density lipoprotein (oxLDL) accelerated the calcification in aorta of rats and rat vascular smooth muscle cells (RVSMCs). However, the molecular mechanism underlying the acceleration remains poorly understood. The present study aimed to investigate the role of calpain-1, Ca2+-sensitive intracellular cysteine proteases, in the vascular calcification of rats treated with both high dose of vitamin D2 and high cholesterol diet. The results showed that calpain activity significantly increased in calcified aortic tissue of rats and RVSMCs treated with oxLDL. Specific calpain inhibitor I (CAI, 0.5mg/kg, intraperitoneal) inhibited the vascular calcification in rats with hypercholesterolemia accompanied by the increase in the level of extracellular inorganic pyrophosphate (PPi), the endogenous inhibitor of vascular calcification. In addition, CAI increased the content of adenosine triphosphate (ATP), decreased the activity, mRNA and protein expression of alkaline phosphatase (ALP) and reduced the production of superoxide anion in calcified aortic tissue. CAI also increased the activity of ATP synthase as well as protein expression of ATP5D, δ subunit of ATP synthase. In the in vitro study, suppression of calpain-1 using siRNA assay inhibited the calcium deposition, increased the levels of PPi and ATP, improved the activity of ATP synthase as well as protein expression of ATP5D in RVSMCs treated with oxLDL. Calpain-1 suppression also decreased the activity, mRNA and protein expression of ALP and reduced the mitochondrial ROS (Mito-ROS) production in RVSMCs. However, mito-TEMPO, the mitochondria-targeted ROS scavenger, reduced the calcium deposition, increased the PPi in culture medium, decreased the activity, mRNA and protein expression of ALP in RVSMCs treated with oxLDL. Taken together, the results suggested that calpain-1 activation plays critical role in vascular calcification caused by oxLDL, which might be mediated by PPi metabolism disorder. The results also implied that Mito-ROS might contribute to the PPi metabolism disorder through regulation of the activity and expression of ALP.

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Calpain cleaves methionine aminopeptidase-2 in a rat model of ischemia/reperfusion

Cited by 15 publications

References 42 publications

Analysis of P67 Expression in Different Mouse Tissues

Analysis of P67 Expression in Different Mouse Tissues

Calpain inhibitor I attenuates atherosclerosis and inflammation in atherosclerotic rats through eNOS/NO/NF-κB pathway

Calpain-1 Mediated Disorder of Pyrophosphate Metabolism Contributes to Vascular Calcification Induced by oxLDL

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