Hydrogen Sulfide Inhibits Ca2+-induced Mitochondrial Permeability Transition Pore (MPTP) Opening in Type-1 Diabetes.

Hydrogen Sulfide Inhibits Ca2+-induced Mitochondrial Permeability Transition Pore (MPTP) Opening in Type-1 Diabetes. Am J Physiol Endocrinol Metab. 2019 Apr 30;: Authors: Papu John AS, Kundu S, Pushpakumar S, Amin M, Tyagi SC, Sen U Abstract Hydrogen sulfide (H2S) attenuates N-Methyl-D-Aspartate receptor-R1 (NMDA-R1) and mitigates diabetic renal damage; however, the molecular mechanism is not well known. While NMDA-R1 facilitates Ca2+ permeability, H2S is known to inhibit L-type Ca2+ channel. High Ca2+ activates cyclophilin D (CypD), a gatekeeper protein of mitochondrial permeability transition pore (MPTP), thus facilitating molecular exchange between matrix and cytoplasm causing oxidative outburst and cell death. We tested the hypothesis whether NMDA-R1 mediates Ca2+ influx causing CypD activation and MPTP opening leading to oxidative stress and renal injury in diabetes. Also, whether H2S treatment blocks Ca2+ channel and thus inhibits CypD and MPTP opening and prevents renal damage. C57BL/6J and Akita (C57BL/6J-Ins2Akita) mice were treated without or with H2S donor GYY (GYY4137, 0.25 mg/Kg/day) intra-peritoneally for 8 weeks. In vitro studies were performed using mouse glomerular endothelial cells (MGECs). Results indicated that low levels of H2S and increased expression of NMDA-R1 in diabetes induced Ca2+ permeability, which was ameliorated by H2S treatment. We observed cytosolic Ca2+ influx in hyperglycemic (HG) condition along w...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research