Modulators of calpain activity: inhibitors and activators as potential drugs

Dókus, Levente Endre; Yousef, Mo’ath; Bánóczi, Zoltán

doi:10.1080/17460441.2020.1722638

Cited by 21 publications

(17 citation statements)

References 163 publications

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“…Their abnormal function is associated with neurodegenerative diseases, cancer, limb-girdle muscular dystrophy type 2A or diabetes mellitus type 2. Their modulators may be useful in therapies of the above diseases [69]. Another enzyme, cyclooxygenase-2 (COX-2), is involved in arachidonic acid metabolism leading to the production of prostaglandin E 2 .…”

Section: Pglmentioning

confidence: 99%

Characteristics of Biopeptides Released In Silico from Collagens Using Quantitative Parameters

Iwaniak

Minkiewicz

Pliszka

et al. 2020

Foods

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The potential of collagens to release biopeptides was evaluated using the BIOPEP-UWM-implemented quantitative criteria including the frequency of the release of fragments with a given activity by selected enzyme(s) (AE), relative frequency of release of fragments with a given activity by selected enzyme(s) (W), and the theoretical degree of hydrolysis (DHt). Cow, pig, sheep, chicken, duck, horse, salmon, rainbow trout, goat, rabbit, and turkey collagens were theoretically hydrolyzed using: stem bromelain, ficin, papain, pepsin, trypsin, chymotrypsin, pepsin+trypsin, and pepsin+trypsin+chymotrypsin. Peptides released from the collagens having comparable AE and W were estimated for their likelihood to be bioactive using PeptideRanker Score. The collagens tested were the best sources of angiotensin I-converting enzyme (ACE) and dipeptidyl peptidase IV (DPP-IV) inhibitors. AE and W values revealed that pepsin and/or trypsin were effective producers of such peptides from the majority of the collagens examined. Then, the SwissTargetPrediction program was used to estimate the possible interactions of such peptides with enzymes and proteins, whereas ADMETlab was applied to evaluate their safety and drug-likeness properties. Target prediction revealed that the collagen-derived peptides might interact with several human proteins, especially proteinases, but with relatively low probability. In turn, their bioactivity may be limited by their short half-life in the body.

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Section: Pglmentioning

confidence: 99%

Characteristics of Biopeptides Released In Silico from Collagens Using Quantitative Parameters

Iwaniak

Minkiewicz

Pliszka

et al. 2020

Foods

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“…Calpain inhibitors protected the myotubes during co-culture by inhibiting both cytosolic and mitochondrial calpain activity. CAST is an endogenous calpain inhibitor, whereas CAPT is a commonly used non-selective and reversible calpain inhibitor; however, they both have off-target effects (9,40,41). Therefore, a genetic approach is required to further clarify the potential role of mitochondrial calpain in CCMA.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Calpains are a family of 15 calcium-activated cysteine proteases, including two ubiquitously expressed members, calpain-1 and calpain-2, and one muscle-specific member, calpain-3 (9,10). Calpastatin (CAST) is the only known ubiquitously expressed endogenous calpain inhibitor (9). Calpains and CAST are generally considered to be localized in the cytoplasm and involved in numerous physiological and disease processes, including muscular dystrophy, diabetes, neurological disorders and hematonosis (11,12).…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of mitochondrial and cytosolic calpain attenuates atrophy in myotubes co‑cultured with colon carcinoma cells

et al. 2020

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“…Calpain, a family of calcium-dependent cysteine proteases, is involved in a wide variety of cellular processes, including remodeling of cytoskeletal/membrane attachments, apoptosis, and inflammation. 22) Recent studies have revealed that calpain activation could promote ER stress. 23) Additionally, our previous studies have demonstrated that calpain activation is involved in pathological processes, such as CVB3 replication, myocardium inflammation, 24) NLPP3 inflammasome-medicated pyroptosis, 25) implying calpain plays pivotal roles in the VMC.…”

mentioning

confidence: 99%

Inhibition of Calpain Alleviates Apoptosis in Coxsackievirus B3-induced Acute Virus Myocarditis Through Suppressing Endoplasmic Reticulum Stress

Shi

Wang

et al. 2021

Int. Heart J.

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Virus myocarditis (VMC) is a common cardiovascular disease and a major cause of sudden death in young adults. However, there is still a lack of effective treatments. Our previous studies found that calpain activation was involved in VMC pathogenesis. This study aims to explore the underlying mechanisms further. Neonatal rat cardiomyocytes (NRCMs) and transgenic mice overexpressing calpastatin (Tg-CAST), the endogenous calpain inhibitor, were used to establish VMC model. Hematoxylin and eosin and Masson staining revealed inflammatory cell infiltration and fibrosis. An ELISA array detected myocardial injury. Cardiac function was measured using echocardiography. CVB3 replication was assessed by capsid protein VP1. Apoptosis was measured by TUNEL staining, flow cytometry, and western blot. The endoplasmic reticulum (ER) stress-related proteins were detected by western blot. Our data showed that CVB3 infection resulted in cardiac injury, as evidenced by increased inflammatory responses and fibrosis, which induced myocardial apoptosis. Inhibiting calpain, both by PD150606 and calpastatin overexpression, could attenuate these effects. Furthermore, ER stress was activated during CVB3 infection. However, calpain inhibition could downregulate some ER stress-associated protein levels such as GRP78, pancreatic ER kinase-like ER kinase (PERK), and inositol-requiring enzyme-1α (IRE-1α), and ER stress-related apoptotic factors, during CVB3 infection. In conclusion, calpain inhibition attenuated CVB3-induced myocarditis by suppressing ER stress, thereby inhibiting cardiomyocyte apoptosis.

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Modulators of calpain activity: inhibitors and activators as potential drugs

Cited by 21 publications

References 163 publications

Characteristics of Biopeptides Released In Silico from Collagens Using Quantitative Parameters

Characteristics of Biopeptides Released In Silico from Collagens Using Quantitative Parameters

Inhibition of mitochondrial and cytosolic calpain attenuates atrophy in myotubes co‑cultured with colon carcinoma cells

Inhibition of Calpain Alleviates Apoptosis in Coxsackievirus B3-induced Acute Virus Myocarditis Through Suppressing Endoplasmic Reticulum Stress

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