title: Sasanquasaponin-induced cardioprotection involves inhibition of mPTP opening via attenuating intracellular chloride accumulation.
abstract: Sasanquasaponin (SQS) has been reported to elicit cardioprotection by suppressing hypoxia/reoxygenation (H/R)-induced elevation of intracellular chloride ion concentration ([Cl-]i). Given that the increased [Cl-]iis involved to modulate the mitochondrial permeability transition pore (mPTP), we herein sought to further investigate the role of mPTP in the cardioprotective effect of SQS on H/R injury. H9c2 cells were incubated for 24h with or without 10μM SQS followed by H/R. The involvement of mPTP was determined with a specific mPTP agonist atractyloside (ATR). The results showed that SQS attenuated H/R-induced the elevation of [Cl-]i, accompanied by reduction of lactate dehydrogenase release and increase of cell viability. Moreover, SQS suppressed mPTP opening, and protected mitochondria, as indicated by preserved mitochondrial membrane potential and respiratory chain complex activities, decreased mitochondrial reactive oxygen species generation, and increased ATP content. Interestingly, extracellular Cl--free condition created by replacing Cl-with equimolar gluconate resulted in a decrease in [Cl-]iand induced protective effects similar to SQS preconditioning, whereas pharmacologically opening of the mPTP with ATR abolished all the protective effects induced by SQS or Cl--free, including suppression of mPTP opening, maintenance of mitochondrial membrane potential, and subsequent improvement of mitochondrial function. The above results allow us to conclude that SQS-induced cardioprotection may be mediated by preserving the mitochondrial function through preventing mPTP opening via inhibition of H/R-induced elevation of [Cl-]i.
authors.affiliation: The Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang 330006, People's Republic of China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Li
authors.affiliation: The Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang 330006, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xiao
authors.affiliation: The Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang 330006, People's Republic of China.
authors.forename: Ling-Yu
authors.initials: LY
authors.lastname: Qiu
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, People's Republic of China.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Yan
authors.affiliation: The Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang 330006, People's Republic of China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang 330006, People's Republic of China.
authors.forename: Guang-Ling
authors.initials: GL
authors.lastname: Duan
authors.affiliation: The Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang 330006, People's Republic of China.
authors.forename: Zhang-Ping
authors.initials: ZP
authors.lastname: Liao
authors.affiliation: The Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang 330006, People's Republic of China. Electronic address: chenheping69@hotmail.com.
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Chen
mesh_terms: D000818:Animals; D001278:Atractyloside / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002460:Cell Line; D002712:Chlorides / Q000737:chemistry*; D003593:Cytoplasm / Q000737:chemistry*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000187:drug effects; D000083162:Mitochondrial Permeability Transition Pore; D032383:Myocytes, Cardiac / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000503:physiopathology; D012503:Saponins / Q000494:pharmacology*
chemical_list: C497504:22-O-angeloylcamelliagenin C-3-O-(glucopyranosyl-1-2)(glucopyranosyl-1-2-O-arabinopyranosyl-1-3-)glucopyranosiduronic acid; D002316:Cardiotonic Agents; D002712:Chlorides; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D012503:Saponins; D001278:Atractyloside
keywords: Atractyloside (PubChem CID: 5702200); Cardioprotection; Hypoxia/reoxygenation injury; JC-1 (PubChem CID: 5492929); MQAE (PubChem CID: 2762651); MTT (PubChem CID: 64965); Mitochondrial permeability transition pore; Penicillin (PubChem CID: 5904); Sasanquasaponin; Streptomycin (PubChem CID: 19649)