Stapled Peptide Inhibitors of Autophagy Adapter LC3B

Cerulli, Robert A.; Shehaj, Livia; Brown, Hawley; Pace, Jennifer R.; Yang, Mei; Kritzer, Joshua A.

doi:10.1002/cbic.202000636

Cited by 4 publications

(3 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, we attempted to clarify whether DAPA activated autophagy pathway and the AMPK/mTOR signaling. LC3B is an adapter protein mediating vital protein-protein interactions in autophagy pathways [21]. Thus, we examined LC3B expression changes in myocardial tissue of rats using IHC.…”

Section: Dapa Facilitates Cardiomyocyte Autophagy In Hf Ratsmentioning

confidence: 99%

Dapagliflozin Inhibits Ventricular Remodeling in Heart Failure Rats by Activating Autophagy through AMPK/mTOR Pathway

2022

Computational and Mathematical Methods in Medicine

View full text Add to dashboard Cite

Objective. Heart failure (HF) is the end stage of heart disease caused by various factors which mainly involves ventricular remodeling (VR). In HF patients with reduced ejection fraction, dapagliflozin (DAPA) reduced the risk of worsening HF or cardiovascular death. Thus, we attempted to clarify the specific role of DAPA underlying HF progression. Methods. The HF rat model was established to mimic characteristics of HF in vivo. HE staining assessed histopathological changes in left ventricular myocardial tissue of rats in each group. ELISA measured plasma ANP and BNP levels of rats in each group. M-mode echocardiography detected cardiac function of rats in each group. TUNEL staining detected apoptosis of infarct margin cells in myocardial tissue of rats in each group. Western blot detected levels of apoptosis-related proteins, autophagy-related proteins, and AMPK/mTOR-related proteins in myocardial tissue of rats in each group. Immunohistochemical staining detected caspase-3 or LC3B level in myocardial tissue of rats in each group. The HF cellular model was established to mimic characteristics of HF in vitro. Flow cytometry detected H9C2 cell apoptosis under different conditions. Western blot detected levels of apoptosis-related proteins, autophagy-related proteins, and AMPK/mTOR-related proteins in H9C2 cells under different conditions. Immunofluorescence detected caspase-3 or LC3B level in H9C2 cells under different conditions. Results. DAPA attenuated left VR and improved cardiac function in HF rats. DAPA attenuated cardiomyocyte apoptosis in HF rats. DAPA facilitated cardiomyocyte autophagy in HF rats via the AMPK/mTOR pathway. DAPA repressed hypoxia-induced H9C2 cell apoptosis by facilitating autophagy. DAPA repressed hypoxia-induced H9C2 cell apoptosis via the AMPK/mTOR pathway. Conclusion. DAPA suppresses ventricular remodeling in HF through activating autophagy via AMPK/mTOR pathway, which provides a potential novel insight for seeking therapeutic plans of HF.

show abstract

Section: Dapa Facilitates Cardiomyocyte Autophagy In Hf Ratsmentioning

confidence: 99%

Dapagliflozin Inhibits Ventricular Remodeling in Heart Failure Rats by Activating Autophagy through AMPK/mTOR Pathway

2022

Computational and Mathematical Methods in Medicine

View full text Add to dashboard Cite

show abstract

“…They further developed a binder with 0:33 ± 0:01 μM affinity against stonin2 and Eps15 interactions from a loop discovered in this analysis. In another study, inspired by the natural binder to LC3B, Cerulli et al used unnatural amino acids and diversity-oriented stapling to obtain high affinity inhibitors of this protein [69].…”

Section: Mutagenesismentioning

confidence: 99%

Design of Protein Segments and Peptides for Binding to Protein Targets

2022

View full text Add to dashboard Cite

Recent years have witnessed a rise in methods for accurate prediction of structure and design of novel functional proteins. Design of functional protein fragments and peptides occupy a small, albeit unique, space within the general field of protein design. While the smaller size of these peptides allows for more exhaustive computational methods, flexibility in their structure and sparsity of data compared to proteins, as well as presence of noncanonical building blocks, add additional challenges to their design. This review summarizes the current advances in the design of protein fragments and peptides for binding to targets and discusses the challenges in the field, with an eye toward future directions.

show abstract

“…Complement factor H (CFH) is a major inhibitor of the complement replacement pathway and an essential protective factor in the retina [4] ; however, the gene variant CFH Y402H increases retinal damage caused by oxidative stress [5] . In addition, autophagy is significantly involved in AMD development [6] , and microtubule-associated protein 1 light chain 3 beta (MAP1LC3B) can increase autophagy [7] . Nevertheless, potential correlations between MAP1LC3B and AMD risk have not been examined to date.…”

Section: Introductionmentioning

confidence: 99%

Association of CFH and MAP1LC3B gene polymorphisms with age-related macular degeneration in a high-altitude population

Ruijuan¹,

Li²,

Kang³

et al. 2022

Int J Ophthalmol

View full text Add to dashboard Cite

AIM: To evaluate the association of complement factor H (CFH) and microtubule-associated protein 1 light chain 3 beta (MAP1LC3B) gene polymorphisms with the risk of age-related macular degeneration (AMD) in a high-altitude population. METHODS: The study group consisted of 172 participants with symptoms of AMD who were examined and diagnosed between January 2019 and June 2020. The control group was composed of 120 healthy individuals. Each participant was required to provide two milliliters of peripheral blood for DNA extraction. Two single nucleotide polymorphisms (SNPs) of CFH (rs1061170 and rs800292) and two SNPs of MAP1LC3B (rs8044820 and rs9903) were genotyped. The genotypes and allele frequencies of the SNPs in the study and control groups were further compared using Chi-square and Fisher’s exact tests. RESULTS: In a high-altitude population, the nominally significant differences of rs800292 and rs9903’s genotype AG frequencies were observed in the AMD group (P=0.034 and 0.004, respectively). The frequencies of allele G of rs800292 and allele A of rs9903 were also significantly different in the AMD group compared to the control [(P=0.034, OR=0.70, 95%CI: 0.50-0.98) and (P=0.004, OR=1.60, 95%CI: 1.15-2.22), respectively]. No significant differences in the genotype distributions (P=0.16 and 0.40, respectively) and allele frequencies (P>0.05) of rs1061170 and rs8044820 were observed in the AMD group. CONCLUSION: Genotype AG of rs800292 may be a protective factor for AMD. Conversely, rs9903 seems to be a risk factor for AMD. Therefore, allele G of rs800292 may be a protective factor, and allele A of rs9903, a risk factor for AMD in Qinghai high-altitude population.

show abstract

Stapled Peptide Inhibitors of Autophagy Adapter LC3B

Cited by 4 publications

References 82 publications

Dapagliflozin Inhibits Ventricular Remodeling in Heart Failure Rats by Activating Autophagy through AMPK/mTOR Pathway

Dapagliflozin Inhibits Ventricular Remodeling in Heart Failure Rats by Activating Autophagy through AMPK/mTOR Pathway

Design of Protein Segments and Peptides for Binding to Protein Targets

Association of CFH and MAP1LC3B gene polymorphisms with age-related macular degeneration in a high-altitude population

Contact Info

Product

Resources

About