Chromogranin A-derived peptides pancreastatin and catestatin: emerging therapeutic target for diabetes

Garg, Richa; Agarwal, Arun; Katekar, Roshan; Dadge, Shailesh; Yadav, Shubhi; Gayen, Jiaur R.

doi:10.1007/s00726-023-03252-x

Cited by 6 publications

(2 citation statements)

References 110 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These first principal findings of CHGA deficiency and decreased CHGA secretion may have clinical phenotype and diagnosis consequences, since chromogranins in the extracellular space and blood stream get cleaved proteolytically into various peptides, which have relevant roles for vascular and metabolic regulation (Garg et al, 2023; Sahu et al, 2019; Troger et al, 2017). As a CHGA cleavage product, Serpinin modulates transcription of PN-1 ( Serpine2 ) that controls LDCV biogenesis (Koshimizu et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

The ataxia-telangiectasia disease protein ATM controls vesicular protein secretion via CHGA and microtubule dynamics via CRMP5

Reichlmeir,

Duecker,

Röhrich

et al. 2024

Preprint

View full text Add to dashboard Cite

The autosomal recessive disease ataxia-telangiectasia (A-T) presents with cerebellar degeneration, immunodeficiency, radiosensitivity, capillary dilatations, and pulmonary infections. Most symptoms outside the nervous system can be explained by failures of the disease protein ATM as Ser/Thr-kinase to coordinate DNA damage repair. However, ATM in adult neurons has cytoplasmic localization and vesicle association, where its roles remain unclear. Here, we defined novel ATM protein targets in human neuroblastoma cells and filtered initial pathogenesis events in ATM-null mouse cerebellum. Profiles of global proteome and phosphorylome - both direct ATM/ATR-phosphopeptides and overall phosphorylation changes - confirmed previous findings on NBN, MRE11, MDC1, CHEK1, EIF4EBP1, AP3B2, PPP2R5C, SYN1 and SLC2A1. Even stronger downregulation of ATM/ATR-phosphopeptides after ATM-depletion was documented for CHGA, EXPH5, NBEAL2 and CHMP6 as key factors of protein secretion and endosome dynamics, as well as for CRMP5, DISP2, PHACTR1, PLXNC1, INA and TPX2 as neurite extension factors. Prominent affection of semaphorin-CRMP5-microtubule signals and ATM association with CRMP5 were validated. As a functional consequence, microtubules were stabilized, and neurite retraction ensued. The ATM impact on secretory granules confirms previous ATM-null cerebellar transcriptome findings. Our study provides the first link of A-T neural atrophy to growth cone collapse and aberrant microtubule dynamics.

show abstract

Section: Discussionmentioning

confidence: 99%

The ataxia-telangiectasia disease protein ATM controls vesicular protein secretion via CHGA and microtubule dynamics via CRMP5

Reichlmeir,

Duecker,

Röhrich

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…[108] CgA and its derivatives have garnered significant attention as potential biomarkers of diabetes and their inhibitors may be new targets for diabetes treatment. [109] Additionally, PSTi8 (a pancreatin inhibitor) enhances mitochondrial function and the oxygen consumption rate in mouse WAT, thereby promoting energy expenditure. [110] Another CgA-derived peptide, catestatin, is an insulin sensitizer [111] and also promotes lipolysis.…”

Section: Mechanisms Of Hypermetabolism In Patients With Ppglmentioning

confidence: 99%

Main mechanisms and clinical implications of alterations in energy expenditure state among patients with pheochromocytoma and paraganglioma: A review

Yang,

Zhou,

Zhao

et al. 2024

Medicine

View full text Add to dashboard Cite

Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with diverse clinical presentations. Alterations in energy expenditure state are commonly observed in patients with PPGL. However, the reported prevalence of hypermetabolism varies significantly and the underlying mechanisms and implications of this presentation have not been well elucidated. This review discusses and analyzes the factors that contribute to energy consumption. Elevated catecholamine levels in patients can significantly affect substance and energy metabolism. Additionally, changes in the activation of brown adipose tissue (BAT), inflammation, and the inherent energy demands of the tumor can contribute to increased resting energy expenditure (REE) and other energy metabolism indicators. The PPGL biomarker, chromogranin A (CgA), and its fragments also influence energy metabolism. Chronic hypermetabolic states may be detrimental to these patients, with surgical tumor removal remaining the primary therapeutic intervention. The high energy expenditure of PPGL has not received the attention it deserves, and an accurate assessment of energy metabolism is the cornerstone for an adequate understanding and treatment of the disease.

show abstract

Chromogranin A and its derived peptides: potential regulators of cholesterol homeostasis

Iyer,

Venkatraman,

Tanguy

et al. 2023

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Chromogranin A-derived peptides pancreastatin and catestatin: emerging therapeutic target for diabetes

Cited by 6 publications

References 110 publications

The ataxia-telangiectasia disease protein ATM controls vesicular protein secretion via CHGA and microtubule dynamics via CRMP5

The ataxia-telangiectasia disease protein ATM controls vesicular protein secretion via CHGA and microtubule dynamics via CRMP5

Main mechanisms and clinical implications of alterations in energy expenditure state among patients with pheochromocytoma and paraganglioma: A review

Chromogranin A and its derived peptides: potential regulators of cholesterol homeostasis

Contact Info

Product

Resources

About