Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 11350192

Reduced skeletal muscle calpain-10 transcript level is due to a cumulative decrease in major isoforms.

X Yang·R E Pratley·L J Baier·Y Horikawa·G I Bell·C Bogardus·P A Permana
View original source ↗Export metadata ↓

Abstract

The DNA polymorphism SNP-43 in the calpain-10 gene is associated with insulin resistance and reduced skeletal muscle transcript in Pima Indians. Alternative splicing generates transcript isoforms calpain-10a to -10h. We determined the contribution of calpain-10 mRNA isoforms to the decreased total skeletal muscle calpain-10 mRNA levels observed in the G/G homozygotes. The expression levels of the major isoforms, calpain-10a and -10f, were positively correlated with the total calpain-10 mRNA levels, indicating a cumulative effect.

Explore related subjects

CalpainFemaleGenotypeHumansIndians, North AmericanIsoenzymesMaleMuscle, SkeletalPolymorphism, GeneticRNA, MessengerTranscription, GeneticJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

X Yang, R E Pratley, L J Baier, Y Horikawa, G I Bell, C Bogardus, P A Permana. 2001. Reduced skeletal muscle calpain-10 transcript level is due to a cumulative decrease in major isoforms.. https://doi.org/10.1006/mgme.2001.3171

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2001

Potent peptide alpha-ketohydroxamate inhibitors of recombinant human calpain I.

A series of potent dipeptide and tripeptide alpha-ketohydroxamic esters was prepared as inhibitors of recombinant human calpain I. Compound 3c, a Cbz-Leu-Phe hydroxamate, displayed the greatest potency against calpain I (IC(50)=6nM), while two compounds, 3l and 3m, both possessing the Cbz-Leu-Leu-Phe sequence, were the most potent (IC(50)=0.2 microM) in a MOLT-4 cell assay.

Calpain↗
PubMed2001

Significance of hydrogen bonding at the S(1)' subsite of calpain I.

alpha-Ketohydroxamates were synthesized as bioisosteres of alpha-ketoamides. The alpha-ketohydroxamates were generally more potent than the corresponding alpha-ketoamides. The potency of the compounds suggests that hydrogen bonding and steric bulk of substituents on the nitrogen atom of the ketoamide moiety influence calpain inhibition.

Calpain↗
PubMed2001

Ester bond-containing tea polyphenols potently inhibit proteasome activity in vitro and in vivo.

It has been discovered that proteasome inhibitors are able to induce tumor growth arrest or cell death and that tea consumption is correlated with cancer prevention. Here, we show that ester bond-containing tea polyphenols, such as (-)-epigallocatechin-3-gallate (EGCG), potently and specifically inhibit the chymotrypsin-like activity of the proteasome in vitro (IC(50) = 86-194 nm) and in vivo (1-10 microm) at the concentrations found in the serum of green tea drinkers. Atomic orbital energy analyses and high performance liquid chromatography suggest that the carbon of the polyphenol ester bond is essential for targeting, thereby inhibiting the proteasome in cancer cells. This inhibition of the proteasome by EGCG in several tumor and transformed cell lines results in the accumulation of two natural proteasome substrates, p27(Kip1) and IkappaB-alpha, an inhibitor of transcription factor NF-kappaB, followed by growth arrest in the G(1) phase of the cell cycle. Furthermore, compared with their simian virus-transformed counterpart, the parental normal human fibroblasts were much more resistant to EGCG-induced p27(Kip1) protein accumulation and G(1) arrest. Our study suggests that the proteasome is a cancer-related molecular target of tea polyphenols and that inhibition of the proteasome activity by ester bond-containing polyphenols may contribute to the cancer-preventative effect of tea.

Calpain↗