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Lipoxygenase‐dependent protection of skeletal muscle contractile function during heat stress
Author(s) -
Oliver S Ryan,
Wright Valerie P,
Zuo Li,
Clanton Thomas L
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a942-c
Subject(s) - nordihydroguaiaretic acid , skeletal muscle , lipoxygenase , chemistry , hyperthermia , cyclooxygenase , medicine , endocrinology , malignant hyperthermia , inflammation , enzyme , biochemistry , pathology
Lipoxygenases (LOXs) are enzymes involved in the restructuring of membrane lipids and the production of leukotrienes. LOX products are best known as mediators of inflammation, which could allude to their importance during times of cellular stress. This study was conducted to test the functional role of LOXs in skeletal muscle during severe heat stress. Contractile function in rat diaphragm bundles was tested after 30 min of hyperthermia (40–43°C). Only at 43°C was there a significant loss of peak force (52.8±7.5% of baseline). General LOX inhibition with nordihydroguaiaretic acid (NDGA) further decreased force at 43°C in a dose dependent manner [e.g. 10μM, 41.2±9.2% of control (P<0.05)] and increased susceptibility to hyperthermia at lower temperatures (41°C). In contrast, specific inhibitors of (5–12‐&15‐LOX) had little or no effect at 43°C. Indomethacin (100μM), a cyclooxygenase (COX) inhibitor, reduced force at 43°C and in combination with NDGA caused nearly complete loss of force at 43°C. In conclusion, global LOX and COX inhibition causes significant loss of muscle contractile function in hyperthermia and their effects are additive. The results suggest that lipid metabolites generated during hyperthermia may be damaging to skeletal muscle and that the integrity of LOX and COX metabolic pathways is critical in preserving skeletal muscle function during conditions of severe hyperthermia. (NHLBI 53333)