The effects of Hemiscorpius lepturus induced-acute kidney injury on PGC-1α gene expression: From induction to suppression in mice. (30th January 2020)

• Record Type: Journal Article
• Authors: Dizaji, Rana; Sharafi, Ali; Pourahmad, Jalal; Vatanpour, Saba; Hosseini, Mir-Jamal; Vatanpour, Hossein
• Is Part Of: Toxicon. Volume 174(2020)
• Page Start: 57
• Page End: 63
• Publication Date: 2020-01-30
• Subjects: Hemiscorpius lepturus -- Heme oxygenase-1 -- PGC-1α -- Nrf-2 -- PPAR-α -- Bax/ Bcl-2; AKI Acute kidney injury -- PGC-1α Peroxisome proliferator-activated receptor γ coactivator 1α -- SOD2 Superoxide dismutase 2 -- GPx 1 Glutathione peroxidase -- Nrf-2 Nuclear respiratory factors -- HO-1 H -- eme oxygenase-1 -- PPAR-α Peroxisome proliferator-activated receptor-α -- ROS Reactive oxygen species -- NADPH nicotinamide adenine dinucleotide phosphate -- BAX Bcl-2-associated X -- Bcl-2 B-cell lymphoma 2 -- MOMP mitochondrial outer membrane permeability -- ND1 NADH dehydrogenase subunit 1; Toxins -- Periodicals; Venom -- Periodicals; 615.9
• DOI: 10.1016/j.toxicon.2019.12.154
• Languages: English
• ISSNs: 0041-0101

Abstract

Abstract: Hemiscorpius lepturus envenomation induces acute kidney injury (AKI) through hemoglubinoria and mitochondrial dysfunction. Mitochondria supports ATP production to promote the regulation of fluid and electrolyte balance. Mitochondrial homeostasis in different metabolic environments can be adjusted by overexpression of PGC-1α. High reactive oxygen species (ROS) production after H. lepturus envenomation and heme oxygenase-1 (HO-1) overexpression causes ATP depletion as well as mitochondrial homeostasis disruption, which lead to progression in renal diseases. The present study aims to evaluate the role of venom induced-AKI in modulating mitochondrial function in cell death and metabolic signaling associated with PPAR-α, PGC-1α, and Nrf-2 as the main transcription factors involved in metabolism. Based on the data, two significant events occurred after envenomation: reduction of gl glutathione level and overexpression of the cytoprotective enzyme HO-1. Apaoptosis induction is associated with a significant decrease in the transcription of PPAR-α, PGC-1α and Nrf-2 after administrating lethal dose of venom (10 mg/kg). Furthermore, at the lower doses of venom (1 and 5 mg/kg), with a significant recovery accompanied with PGC-1α upregulation occurs after AKI. As the findings indicate, PGC-1α has a key role in restoring the mitochondrial function at the recovery phase of mouse model of AKI, which highlights the PGC-1α as a therapeutic target for venom induced-AKI prevention and treatment. Highlights: Mitochondrial homeostasis following AKI condition is related to PGC-1α overexpression in response to glutathion depletion. PGC-1α as a therapeutic target for H. lepturus induced-AKI prevention is involved in restoring of mitochondrial mass. In sever envenomation condition, transcript level of Nrf2 is significantly suppressed preposition to HO-1 upregulation. Nrf-2 is not the main transcription factors in HO-1 signaling.