title: Metabolic stability of human parathyroid hormone peptide hPTH (1-34) in rat tissue homogenates: kinetics and products of proteolytic degradation.
abstract: The present study aim to investigate the metabolic stability and degradation of cleavage sites of human parathyroid hormone peptide, hPTH (1-34), in rat tissue homogenate, and to identify the types of proteases involved in hPTH (1-34) processing degradation. The stability of hPTH (1-34) in rat kidney, lung and liver homogenates was evaluated by LC-ESI-MS, and the structures of the major degradation products were identified by MALDI-TOF MS and LC-ESI-MS/MS. The ability of protease inhibitors to inhibit hPTH (1-34) degradation was used to identify the class of proteases involved in the metabolism of hPTH (1-34). hPTH (1-34) peptide was readily degraded in rat kidney, liver, and lung homogenates, with half-lives of 5.7, 32.2, and 18.9 min, respectively. The degradation of hPTH (1-34) in each tissue can be inhibited by inhibitors of serine and metalloproteases. The major degradation products of hPTH (1-34) are similar in each tissue and suggest that hPTH (1-15) and hPTH (16-34) appear as the major degradation products. The degradation patterns of hPTH (1-34) incubated in rat kidney, liver and lung homogenates are largely overlapping, and a majority of the fragments are generated via cleavages at sites of Leu15-Asn16 peptide bond.
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Haidian District, 100850, Beijing, People's Republic of China.
authors.forename: Sha
authors.initials: S
authors.lastname: Liao
authors.forename: Jian-Kun
authors.initials: JK
authors.lastname: Qie
authors.forename: Ming
authors.initials: M
authors.lastname: Xue
authors.forename: Zhen-Qing
authors.initials: ZQ
authors.lastname: Zhang
authors.forename: Ke-Liang
authors.initials: KL
authors.lastname: Liu
authors.forename: Jin-Xiu
authors.initials: JX
authors.lastname: Ruan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D010281:Parathyroid Hormone / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D010281:Parathyroid Hormone